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8220777
Lectins: reliable differentiation markers in human oligodendrogliomas.
Ninety tumours classified as well-differentiated oligodendrogliomas (43 cases) and anaplastic oligodendrogliomas (47 cases) were studied with glial fibrillary acidic protein (GFAP) and bound with different lectins including: peanut agglutinin (PNA), concanavalin A (Con A), wheat germ agglutinin (WGA) and Ricinus communis agglutinin (RCA-1). PNA has shown high affinity to cellular membranes of well-differentiated oligodendrogliomas. The affinity decreases with the cellular differentiation to astrocytic lines and is lost in anaplastic oligodendrogliomas. Con A labelling is restricted to anaplastic oligodendroglioma cells and to reactive astrocytes showing a predominant somatic (cytoplasmatic) pattern of staining. Our findings showed that a combined search with GFAP and lectins may allow an accurate grading of oligodendrogliomas.
Adolescent,Adult,Aged,Child,Child, Preschool,Concanavalin A,Female,Humans,Lectins,Male,Middle Aged,Oligodendroglioma,Peanut Agglutinin,Plant Lectins,Wheat Germ Agglutinins
null
8220778
Lectin histochemistry of dermoid and epidermoid cysts of the central nervous system.
The binding affinities of seven lectins to four epidermoid and three dermoid cysts were studied and the results were compared with the epidermis and the oral mucosa. The reactivity of four epidermoid cysts of the fourth ventricle and the frontal lobe, and one dermoid cyst in the sylvian fissure was consistent with that of the skin, whereas the binding profile of one parasellar dermoid cyst was identical to that of the keratinized oral mucosa. Another parasellar dermoid cyst also showed close similarity to the buccal mucosa. These results indicate that cells of these cysts develop same glycoconjugates as do normal epithelial cells, and some of these cysts around the sellar region might be derived from the cells of the oral mucosa.
Adolescent,Adult,Aged,Central Nervous System Diseases,Central Nervous System Neoplasms,Dermoid Cyst,Epidermal Cyst,Epidermis,Female,Histocytochemistry,Humans,Lectins,Male,Middle Aged,Mouth Mucosa
null
8220779
Phenotypic alteration of glioma cells during culture.
Tissue specimens and culture cells from three human gliomas (two astrocytomas and one glioblastoma) were immunohistochemically investigated, using GFAP, S-100P, vimentin, FN and TNF antibodies. Primary culture consisted of two cell types, flat cells and fibrous cells. Phenotypic alternation was observed during successive subculture. Differences between fibrous cells in astrocytoma and those in glioblastoma were remarkable, while flat cells in astrocytoma and glioblastoma examined in this study, were similar.
Adult,Astrocytoma,Child,Fibronectins,Glial Fibrillary Acidic Protein,Glioblastoma,Glioma,Humans,Immunohistochemistry,Male,Phenotype,S100 Proteins,Tumor Cells, Cultured,Tumor Necrosis Factor-alpha,Vimentin
null
8220780
Radiosensitive squamous cell craniopharyngioma: clinical and pathological comparison with the adamantinomatous type.
Five patients with the squamous cell type of craniopharyngioma were examined clinically and pathologically, and comparisons were made with the adamantinomatous type of craniopharyngioma. In three patients, the tumor remaining after partial or subtotal resection was treated with conventional radiation therapy, and all three lesions disappeared completely. The squamous cell tumors consisted of basal cubodial cells and polygonal superficial cells with areas of cellular detachment and degeneration. Our findings suggest that these tumors are more radiosensitive than adamantinomatous craniopharyngiomas and represent a distinct clinical entity.
Adult,Combined Modality Therapy,Craniopharyngioma,Female,Gamma Rays,Humans,Magnetic Resonance Imaging,Male,Middle Aged,Pituitary Neoplasms,Radiosurgery,Tomography, X-Ray Computed,Treatment Outcome
null
8220781
Clinical, biological and histological considerations on primary intracranial germinomas in the prevalent sites.
Twenty-four germinomas from which tumor sites were 11 pineal, 7 suprasellar, and 6 basal ganglial and thalamic (BG-T) were subjected. Humoral tumor markers of HCG, CEA and AFP were measured and compared with immunohistochemistries for these tumor markers along with PLAP, HPL and PKK1. Humoral tumor markers and immunohistochemistries did not always comprehend to each other. Difference of the survival rates among tumor sites was thought to be attributed to the variabilities in their histological, immunochemical and flow cytometric results.
Adolescent,Adult,Biomarkers, Tumor,Brain Neoplasms,Child,Child, Preschool,Combined Modality Therapy,DNA, Neoplasm,Female,Flow Cytometry,Germinoma,Humans,Immunohistochemistry,Male,Microscopy, Electron,Tomography, X-Ray Computed
null
8220782
Anaplastic astrocytoma in the cerebellopontine angle.
In this paper we present a case of glioma which was located in the cerebellopontine angle. The patient, a 3-year-old male, experienced difficulty with gait for one month before admission. He was admitted to Toyota Memorial Hospital on February 2, 1991, suffering from severe headache and vomiting. Neurological examination upon admission revealed horizontal nystagmus and ataxia. MRI revealed a mass in the cerebellopontine angle. Craniotomy was performed on February 4, 1991, and a tumor was revealed in the cerebellopontine angle. The tumor was clearly demarcated and encapsulated; the cerebellum and brainstem were compressed without damage. Most of the tumor was removed. A histopathological summary of the tumor follows. The tumor appeared as exophytic lesions on the pons, extending into the cerebellopontine angle. Tumor cells contained small round nuclei and acidophilic cytoplasm. The oncocyte, which was growing endomorphically, revealed a short-cell projection, suggesting a tendency to penetrate blood vessels. Intercellular microcystic degeneration was observed clearly, with some parts of the oncocyte forming a myxoid matrix. Immunohistochemically, most of the tumor cells reacted positively to Vimentin, but negatively to S-100 protein and GFAP. Given the pathological information, the tumor was interpreted as anaplastic astrocytoma. Postoperative radiation therapy was performed, but the patient died four months later because the tumor had spread to the brainstem. In this paper we discuss the differential diagnosis of the cerebellopontine angle tumor and the appearance of anaplastic astrocytoma as exophytic lesions on the pons and the spread of the tumor into the cerebellopontine angle.
Brain Neoplasms,Cerebellopontine Angle,Child, Preschool,Glioblastoma,Humans,Magnetic Resonance Imaging,Male
null
8220783
Immunohistochemical studies on choroidal epithelial cyst and neuroepithelial cyst: in comparison with normal choroid plexus and ependyma.
Immunohistochemical evaluations with antibodies against S-100 protein, glial fibrillary acidic protein, cytokeratin and prealbumin were applied to 2 intracranial cysts of choroidal epithelial and neuroepithelial origin, and to the normal choroid plexus and ependyma. All specimens showed various immunoreactivities with the 4 antigens: especially, prealbumin-positive cells were detected in normal choroid plexus, part of normal ependyma, and part of choroidal epithelial cyst. The epithelium of neuroepithelial cysts presumably has multipotentials in cellular differentiation.
Brain Diseases,Choroid Plexus,Cysts,Ependyma,Female,Humans,Immunohistochemistry,Infant,Male,Microscopy, Electron,Reference Values
null
8220784
Clinicopathological study on craniopharyngioma with sebaceous differentiation.
We presented 2 cases of craniopharyngioma, which showed sebaceous differentiation. Both cases shared the following features: 1) neuroradiological detection of a cystic tumor accompanied by calcification, 2) clear yellowish fluid detected in the cyst during surgery, 3) histological rating as an adamantinomatous type, 4) the presence of a nest-like distribution of multivacuolated cells in the innermost layer of the cyst.
Child,Contrast Media,Craniopharyngioma,Gadolinium DTPA,Humans,Immunohistochemistry,Magnetic Resonance Imaging,Male,Middle Aged,Organometallic Compounds,Pentetic Acid,Pituitary Neoplasms,Sebaceous Glands
null
8220785
Autoradiographic analysis of (14C-methyl)-L-methionine uptake in transplanted rat brain tumors.
To elucidate metabolic pathways of methionine in brain tumors, we studied autoradiographic images of (14C-methyl)-L-methionine (14C-Met) in transplanted rat brain tumors. 14C-Met accumulated in the tumor almost twice as much as in the gray matter 90 min after injection. The acid-insoluble fraction, which was bound to macromolecules, comprised 84% the total count of the accumulated tracers in the tumor. Analysis of 14C-Met tracer accumulation is informative for understanding amino acid metabolism in brain tumors.
Animals,Autoradiography,Brain Neoplasms,Carbon Radioisotopes,Male,Methionine,Neoplasm Transplantation,Rats,Rats, Sprague-Dawley,Tumor Cells, Cultured
null
8220786
Medulloblastoma associated with malignant rhabdoid tumor of the kidney: case report.
The authors report a case of 6-month-old boy with cerebellar medulloblastoma associated with malignant rhabdoid tumor of the kidney, presenting with an abdominal mass, large head and projectile vomiting. Following removal of the renal tumor, the mass arising from the superior vermis about 6 cm in diameter was removed by a combined right occipital transtentorial and suboccipital approach. The patient had been well for 3 months after surgery followed by chemotherapy but died eventually of tumor recurrence in the abdomen. Reported cases of malignant rhabdoid tumor of the kidney associated with brain tumor are reviewed and its characteristics are discussed.
Cerebellar Neoplasms,Humans,Infant,Kidney Neoplasms,Magnetic Resonance Imaging,Male,Medulloblastoma,Neoplasms, Multiple Primary,Rhabdoid Tumor,Tomography, X-Ray Computed
null
8220787
Ossifying cementicular fibroma of the orbitofrontal bone in a child: case report.
A rare case of ossifying cementicular fibroma of the left orbitofrontal bone that developed in a 12-year-old boy is presented. A hard, painless mass that was incidentally noticed gradually enlarged over 2 years. Skull X-rays showed a well-demarcated lesion with mixed sclerotic and osteolytic radiolucent changes in the left orbitofrontal bone. Computed tomography revealed an expansile intradiploic multilocular mass that was separated by bony trabeculae. T1-weighted magnetic resonance imaging demonstrated a multi-cystic iso-intense mass with homogeneous contrast enhancement. Left external carotid angiograms revealed a vague tumor stain that was mainly fed by the middle meningeal artery. Systemic bone scintigrams revealed a single abnormal uptake in the lesion. The skull tumor was totally removed. Histological examination demonstrated two different characteristic findings that were composed of fibrous dysplasia and cementifying fibroma, although most of the tumor appeared to be a highly cementicular form of fibro-osseous lesion. The pathological diagnosis was a cementicular variant of fibrous dysplasia.
Child,Fibroma, Ossifying,Frontal Bone,Humans,Male,Odontogenic Tumors,Orbital Neoplasms,Skull Neoplasms,Tomography, X-Ray Computed
null
8220788
A case of sellar chordoma mimicking a non-functioning pituitary adenoma with survival of more than 10 years.
A rare case of sellar chordoma occurring in a 67-year-old woman who survived for more than 10 years is presented. Clinical signs and symptoms masqueraded as a non-functioning pituitary adenoma with visual disturbance and hypopituitarism. Initial computed tomography (CT) showed an intrasellar mixed dense mass with suprasellar extension, accompanied by non-homogeneous contrast enhancement. Partial removal of the mass was accomplished via right fronto-temporal craniotomy. Histological examination revealed a typical chordoma with no malignancy. After postoperative irradiation, the patient was discharged with clinical improvement. Serial CT and magnetic resonance imaging 8 years after treatment disclosed a regrowth of the intrasellar lesion, which extended to the sphenoid sinus and clivus, accompanied by non-homogeneous contrast enhancement. The patient underwent subtotal removal of the recurrent tumor through a sublabial transsphenoidal approach. Histological examination confirmed the previous diagnosis. Immunohistochemical study demonstrated positive cytoplasmic expression of vimentin, epithelial membrane antigen, keratin and S-100 protein, in contrast with a lack of appearance of carcinoembryonic antigen. After reoperation, she completely recovered and has survived for more than 10 years with good quality of life.
Adenoma,Aged,Chordoma,Diagnosis, Differential,Female,Humans,Immunohistochemistry,Magnetic Resonance Imaging,Mortality,Neoplasm Recurrence, Local,Pituitary Neoplasms,Skull Neoplasms,Time Factors,Tomography, X-Ray Computed
null
8220789
Immunohistochemical study of copper and zinc-superoxide dismutase (Cu, Zn-SOD) in meningiomas.
A localization of copper and zinc-superoxide dismutase (Cu, Zn-SOD) in meningiomas was examined with immunohistochemical technique. Meningiomas include five meningotheliomatous, five transitional, two fibroblastic, and one of each angioblastic, malignant and hemangiopericytic types. The Cu, Zn-SOD localized diffusely in the cytoplasm of tumor cells and in the endothelial cell of vessels and neutrophils, macrophages and red blood cells in the vessels or in the tumor tissue. The Cu, Zn-SOD content in meningiomas was markedly higher in angioblastic, malignant and hemangiopericytic than in meningotheliomatous, transitional and fibroblastic types.
Adult,Aged,Antibodies, Monoclonal,Female,Humans,Immunohistochemistry,Male,Meningeal Neoplasms,Meningioma,Middle Aged,Superoxide Dismutase,Tissue Distribution
null
8220790
Poorly differentiated orbital rhabdomyosarcoma with intracranial extension: a case report.
The authors report a case of poorly differentiated orbital rhabdomyosarcoma with intracranial extension in a 5-month-old female. The clinical and pathologic characteristics are discussed with reference to the differential diagnosis.
Female,Humans,Immunohistochemistry,Infant,Neoplasm Invasiveness,Orbital Neoplasms,Rhabdomyosarcoma,Skull,Tomography, X-Ray Computed
null
8220791
Origin of craniopharyngioma: an electron microscopic study.
To investigate the possibility that the two subtypes of craniopharyngioma, adamantinous type and squamous papillary type, are tumors arising from different origins, the authors conducted an electron microscopic study in 10 cases of craniopharyngioma. Light microscopic study revealed distinct differences between the two subtypes, but their ultrastructure was fundamentally similar. In this report, the authors propose an explanation of the origin of these subtypes to account for the findings.
Adolescent,Adult,Craniopharyngioma,Humans,Microscopy, Electron,Pituitary Neoplasms
null
8220792
Malignant nerve sheath tumor of the jugular foramen followed by meningeal dissemination in a patient with neurofibromatosis.
A 20-year-old female with von Recklinghausen's disease became aware of hoarseness and dysphagia with a right neck mass, and received subtotal resection of a jugular foramen neurofibroma. One year later the jugular foramen tumor recurred and pathologic examination at excision showed a malignant transformation. Despite postoperative chemotherapy and radiotherapy, it recurred soon and followed the metastatic cerebral tumor by meningeal dissemination. Malignant nerve sheath tumors of the jugular foramen are very rare and the clinical course and pathological pictures of this tumor are reviewed.
Adult,Cerebellar Neoplasms,Cranial Nerve Neoplasms,Female,Humans,Magnetic Resonance Imaging,Meninges,Neoplasm Recurrence, Local,Neurofibroma,Neurofibromatoses,Tomography, X-Ray Computed
null
8220793
Malignant astrocytoma with extracranial metastases: a case report.
A 41-year-old man was referred to this hospital after being diagnosed as suffering from malignant astrocytoma. In spite of two operations and subsequent chemoradiation therapy, the patient died 20 months after the onset of disease. At autopsy, the authors found skin invasion of tumor at left temporal region, softening of the brain and subarachnoid hemorrhage at the base of the brain. Yellowish-white bulging lesions were found at the bottom of left lung, diaphragm and parietal pleura. Histologically, primary lesion showed features of anaplastic malignant astrocytoma. Subarachnoid dissemination was noted at the base of the brain and in the spinal canal. Invasion into the vessels were observed both at the primary site and at the base of the brain. Glial fibrillary acidic protein positive spindle-shaped tumor cells proliferation was seen in the metastatic lesions. This case was diagnosed as malignant astrocytoma with remote extracranial metastases.
Adult,Astrocytoma,Brain,Brain Neoplasms,Humans,Male,Neoplasm Invasiveness,Skin,Spinal Canal,Tomography, X-Ray Computed
null
8220794
Histological and ultrastructural findings of benign intracranial cysts.
Since benign intracranial cysts have similar clinical and neuroradiological imaging appearances, it is difficult to distinguish between these cysts. Thus an electron microscopic study plays an important role in definite diagnosis of these non-tumorous benign cystic lesions, and also in determination of their origins. Arachnoid cysts occurring in 5 patients, epithelial cysts occurring in 2 patients, 2 cases of Rathke's cleft cysts, and one case of pineal cyst, were electron- and light-microscopically observed, and their characteristic features and differences were described. The structure of the arachnoid cyst wall was similar to that of normal arachnoid membrane. The inner surface of the arachnoid membrane. The inner surface of the arachnoid cyst wall was formed of one or several layers of arachnoid cells with slender processes, which contained large extracellular spaces, but not microvilli. As for epithelial cysts, microvilli and surface-coating material were present on the surface of epithelial cysts, and a well-developed basement membrane was continuously observed under the epithelial cells. Rathke's cleft cysts, which may basically be classified as epithelial cysts, are lined by columnar or cuboidal ciliated epithelium. The wall of the pineal cyst is composed of normal pineal tissue, and there are three layers, which have a lining of glial cells in the inner layer, a few sheets of pineal cells in the middle layer, and a fibrous capsule in the outer layer.
Adult,Aged,Arachnoid Cysts,Brain Diseases,Brain Neoplasms,Child,Craniopharyngioma,Cysts,Epithelium,Female,Humans,Infant,Male,Microscopy, Electron,Middle Aged,Pineal Gland,Pituitary Neoplasms
null
8220795
Secretory meningioma: a case report with immunohistochemical and ultrastructural study.
Secretory meningioma is a new concept proposed with the progress on immunohistochemistry, and has not sufficiently been discussed in the literature. We report a case with this rare type of meningioma, in a 54-year-old female. The tumor had hyaline inclusions that showed not only carcinoembryonic antigen (CEA) on immunohistochemical study but some secreting organelles on ultrastructural study. The value of these findings are emphasized in the histological diagnosis for secretory meningioma.
Carcinoembryonic Antigen,Female,Humans,Immunohistochemistry,Inclusion Bodies,Magnetic Resonance Imaging,Meningeal Neoplasms,Meningioma,Microscopy, Electron,Middle Aged,Tomography, X-Ray Computed
null
8220796
Vacuolated meningioma with secretory features: a case report.
We report a case of meningioma with secretory features in a 47-year-old woman. The left frontal tumor mass had already eroded the overlying bone at the time of presentation. When respected, the mass showed a gelatinous appearance. Histologically, marked vacuolar change was seen in the stroma. Whorls, psammoma bodies, and pavement arrangement of nuclei were also noted. Periodic acid-Schiff stain revealed cytoplasmic granules, which were digested with diastase. Alcian blue diffusely stained the cytoplasm of the tumor cells. Electron microscopy showed numerous small vacuoles and cored vesicles in the cytoplasm. Glycogen granules were poorly observed. These features indicate the mild secretory nature of this vacuolated meningioma.
Female,Humans,Meningeal Neoplasms,Meningioma,Microscopy, Electron,Middle Aged,Periodic Acid-Schiff Reaction,Vacuoles
null
8220799
Prevalence of atopic disease among Danish school children.
As a result of a 1990 survey by questionnaire, the symptoms of atopy among all 4,952 school children aged 5 to 16 years in the municipal district of Viborg, Denmark, were registered. Random checks, made among children who were recorded as having symptoms, and others who were recorded as having none, accorded well with the information supplied by the parents about symptoms and the clinical diagnosis of a specialist; 10.5% of all school children had rhinitis, 7% had atopic eczema, 3.2% had urticaria and 4.5% had asthma; 1/4 of all those questioned had shown symptoms within the last year, and a further 13% of all the children were reported as having had atopic symptoms that had disappeared more than a year previously. Of the children showing symptoms within the last year before the survey, 2/3 had gone to a doctor. Of the children with present symptoms, largely asthma, 1/4 had been referred to a hospital allergy clinic. For 1/3 of the children with present symptoms, these had led to no contact with a doctor. Of the cases with present symptoms, 6.5% had had contact with natural healers or chiropractors. Rhinitis and asthma were most frequent among boys, while atopic eczema was most frequent among girls. For both sexes, the frequency of rhinitis increased during their years at school, while the frequency of skin symptoms fell.
Adolescent,Age Factors,Child,Child, Preschool,Denmark,Female,Humans,Hypersensitivity,Male,Prevalence
2058810,2621026,2695307,3621551,3810929
8220800
Prevalence of intolerance to food additives among Danish school children.
The prevalence of intolerance to food additives was assessed in a group of unselected school children aged 5-16 years. A study group of 271 children was selected on the basis of the results of a questionnaire on atopic disease answered by 4,274 (86%) school children in the municipality of Viborg, Denmark. The children in the study group followed an elimination diet for two weeks before they were challenged with a mixture of food preservatives, colourings and flavours. The challenge was open and the additives were prepared as a fizzy lemonade. If the open challenge was positive, a double-blind placebo controlled challenge with gelatine capsules was performed. The study included 281 children, 10 were excluded, and the remaining 271 children were given the open challenge (98 healthy controls and 173 with atopic symptoms). The open challenge was negative in all 98 healthy control children who had not reported any atopic symptoms. Of the 173 children reporting present or previous atopic disease 17 had a positive open challenge. Of these 17 children 1 experienced gastrointestinal symptoms, 13 reacted with aggravation of atopic eczema, and 3 with urticaria. Twelve of these 17 children went through the double-blind challenge which was positive in 6 cases. Five of these 6 children had positive reactions to synthetic colourings and 1 to citric acid. No serious reactions were seen. Based upon calculations of the results from this study and an earlier multi-center study in children referred to hospital clinics, the prevalence of intolerance to food additives in school children is estimated to be 1-2%.
Adolescent,Child,Child, Preschool,Denmark,Double-Blind Method,Female,Food Additives,Food Hypersensitivity,Humans,Male,Prevalence
2411075,2610332,2876337,3291786,3961968,6295125,8220799
8220801
Atopic family history. Validation of instruments in a multicenter cohort study.
In order to identify newborns at risk for atopic diseases, we developed a family questionnaire and selected specific answers which were suitable to identify atopic family members. The validity of the questionnaire was evaluated by the Phadiatop test results of 793 mothers and 353 fathers. As both screening instruments do not measure the same, the Phadiatop test identifies sensitization to inhalant allergens and the history reflects the clinical manifestation of atopic disease, the agreement between sensitization and manifestation is incomplete. Sensitivity and specificity of the questionnaire screening conditions to reproduce the Phadiotop test result was 64% and 84% for mothers, and 58% and 88% for fathers, respectively. The relative risk for lifetime prevalence of atopic manifestations in Phadiatop positive over negative mothers was calculated to be 3.88 (95% confidence interval = 3.12 to 4.81), and for Phadiatop positive over negative fathers to amount 4.84 (95% confidence interval 3.25 to 7.23). A few relevant answers of 20 were identified by logistic regression analysis to predict the Phadiatop test result nearly, as well as the total questionnaire.
Adult,Cohort Studies,Family,Female,Humans,Hypersensitivity,Immunoglobulin E,Male,Radioallergosorbent Test,Radioimmunoassay,Risk,Surveys and Questionnaires
1777833,2357615,2382793,2758355,3069000,3336575,6465625,7172766
8220802
Vacuum cleaning decreases the levels of mite allergens in house dust.
To investigate the capacity of chemical treatment of surfaces and the difference in capacity among common vacuum cleaners to reduce mite allergen content in house dust, we recruited 52 families with allergic children. Ten families used their central vacuum cleaners. Forty-two families were randomly divided into four groups with 10 or 11 families in each. These families used either new vacuum cleaners with either HEPA (High Efficiency Particulate Air) or micro-filters, or their own vacuum cleaners with either tannic acid or placebo. Dust samples were collected from carpets and upholstered furniture in the living rooms and from the mattresses of the children at Days 0, 7, 21, and 35. Der pI and Der fI allergens were determined by sandwich ELISA. After one week, tannic acid reduced the concentration of mite allergens/g of dust and the total amount/sampling area by 30% and 34%, respectively (p < 0.05), but there was no significant decrease in relation to placebo. After 5 weeks, central, HEPA- and micro-filter vacuum cleaners decreased the mite allergen concentration by 10-50% (p < 0.05) and the total amount of mite allergen from the investigated areas by 50-85% (p < 0.01). In relation to the placebo group the decrease was significant for HEPA- and micro-filter vacuums (p < 0.05). The total amount of mite allergens/sampling area was more significantly (p < 0.05) reduced than the concentration/g of dust. We conclude, that tannic acid reduces mite allergen concentrations in dust and total amount/sampling area for a short period of time.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergens,Animals,Dust,Environment, Controlled,Household Work,Mites,Vacuum
1159731,1356194,1514665,1551036,1560167,1607553,1976929,2071788,2191991,2478606,2926155,3341627,6342456,6846741,6881682,7037223,7076994,7305119
8220803
Nasal powder administration of budesonide for seasonal rhinitis in children and adolescents.
The effect of intranasal budesonide delivered from a new dry powder inhaler (Rhinocort Turbuhaler) was evaluated in a randomized, double blind, group parallel study of 83 children aged 4-16 years with seasonal allergic rhinitis. The doses 100 and 200 micrograms taken once daily in each nostril were compared with placebo. A one week run-in period was followed by a 4 weeks treatment period. Diary recordings of nasal symptoms, p.r.n. use of terfenadine tablets were made at home and rhinoscopy performed at hospital before and at the end of each treatment period. Total or substantial control of symptoms was achieved in 41% of the children in the 400 micrograms group (p < 0.05 compared with placebo), in 33% in the 200 micrograms group (p = 0.07 compared with placebo) and in 14% in the placebo group. The 400 micrograms but not the 200 micrograms group was statistically significantly better than placebo for most of the clinical effect parameters studied. The treatment was well tolerated and a battery of laboratory tests including cortisol excretion in the urine was not influenced by the various treatments. These results indicate that 400 micrograms budesonide given once daily from a Rhinocort Turbuhaler is clinically effective and safe in children with rhinitis. Further studies are needed to evaluate if this inhaler is preferable to other inhalers currently used for the treatment of rhinitis.
Administration, Inhalation,Adolescent,Budesonide,Child,Child, Preschool,Double-Blind Method,Female,Humans,Male,Powders,Pregnenediones,Rhinitis, Allergic, Seasonal
1467613,1527313,1789399,1891681,3912192
8220804
Cetirizine for seasonal allergic rhinitis in children aged 2-6 years. A double-blind comparison with placebo.
A total of 107 children of both sexes between 2 and 6 years of age with pollen-induced seasonal allergic rhinitis (SAR) were entered in a multicentre study of double-blind parallel group design in which the effects of 5 mg cetirizine, given as drops from a solution containing 10 mg/ml once daily each evening for two weeks, were compared with those of identical placebo. Sneezing, rhinorrhea, nasal obstruction and nasal and ocular pruritus were the symptoms evaluated by means of symptom scores by investigators and, on daily record cards, by parents. Investigators also made a global evaluation at the end of treatment. Cetirizine was more active than placebo for each symptom evaluated both by parents and investigators. There were significant by more (p = 0.002) days during which symptoms were absent or mild, in the cetirizine than in the placebo group. When the maximum symptom scores rated by investigators at each visit were compared, the difference in favour of cetirizine at the end of treatment was statistically significant (p = 0.04). Global evaluation by investigators of changes in symptoms at the end of the study showed an improvement in both groups which was significantly greater with cetirizine, providing excellent or good improvement in 34/54 patients compared with 25/53 patients on placebo (p = 0.039). Tolerance was good. Three patients on cetirizine and none on placebo experienced mild somnolence.
Cetirizine,Child,Child, Preschool,Double-Blind Method,Female,Humans,Male,Rhinitis, Allergic, Seasonal
1979800,1979802,8353660
8220807
Decision making with pregnant patients: a policy born of experience.
One hospital has developed an institutional policy to guide decision making between physicians and pregnant patients. Read the policy and a description of how it was developed by the ethics committee at the George Washington University Hospital.
Adult,Cesarean Section,Decision Making,District of Columbia,Ethics Committees,Ethics Committees, Clinical,Expert Testimony,Female,Hospitals, University,Humans,Infant, Newborn,Informed Consent,Judicial Role,Legal Guardians,Malpractice,Maternal-Fetal Relations,Organizational Policy,Personal Autonomy,Pregnancy,Pregnant Women,Risk Management,Social Values
2045276,2703337,3276942,3574370,4022506
8220808
Letter from the Interest Group on Health Services Research, Association of Academic Health Centers.
Although guidelines have existed in various forms for many years, increased interest in guidelines has sparked myriad concerns among health care professionals, policymakers, and the broader public. Among these concerns are a number of legal questions that to date have not received sufficient notice or study.
Academic Medical Centers,Health Services Research,Humans,Information Services,Malpractice,Practice Guidelines as Topic,Quality Assurance, Health Care,United States
null
8220810
Clinical practice guidelines: policy issues and legal implications.
The growing interest in clinical practice guidelines is raising a number of complex legal questions that have yet to be widely examined. Could physicians be held liable if they disregard good medical judgement in favor of following cost containment guidelines? To what extent should developers and implementers of guidelines be granted civil immunity from liability? How will judges respond to guidelines as evidence, and how will they react when various guidelines conflict?
Cost Control,Health Care Rationing,Health Policy,Humans,Liability, Legal,Malpractice,Practice Guidelines as Topic,Quality Assurance, Health Care,Technology, High-Cost,United States
1580720,1597913,1906073,1942459,2110350,2110352,2110355,2110357,2110358,2110359,10114977
8220811
Overview: prospects and options for local and national guidelines in the courts.
Local adaptation of national guidelines appears to be widespread, but it is little examined in terms of its extent, appropriateness, and impact. But the worst situation for patient and practitioner would be when a good national guideline exists but a bad local guideline guides practice.
Cost Control,Health Policy,Health Services Misuse,Humans,Practice Guidelines as Topic,Quality Assurance, Health Care,United States
null
8220812
Overview of legal issues.
Evidence suggests that compliance with guidelines will affect malpractice litigation. One point often overlooked is that guidelines can provide both exculpatory and inculpatory evidence.
Cost Control,Defensive Medicine,Health Services Misuse,Humans,Practice Guidelines as Topic,Quality Assurance, Health Care,United States
null
8220813
Use of practice parameters as standards of care and in health care reform: a view from the American Medical Association.
Guidelines that are standards of care could limit the creative initiatives to find ways of caring for patients which do not conform to traditional medical practice but result in good outcomes. Physicians would likely feel hemmed in by guidelines that constitute an express legal standard of care and would be afraid to deviate from them except under the auspices of carefully controlled research protocols.
American Medical Association,Attitude of Health Personnel,Cost Control,Health Care Reform,Humans,Liability, Legal,Malpractice,Practice Guidelines as Topic,Quality Assurance, Health Care,Treatment Outcome,United States
1341934,1906073,1942453,1942459,2110350
8220814
The use of guidelines to reduce costs and improve quality: a perspective from the insurers.
The natural concern is the abuse of guidelines--most commonly, from using them as rules, either applying them incorrectly or attempting to micromanage care through them. Both corporate customers and insurers are greatly concerned about these issues and have policies to avoid such abuse.
Cost Control,Forecasting,Health Care Costs,Humans,Insurance Claim Review,Insurance, Health,Managed Care Programs,Practice Guidelines as Topic,Quality Assurance, Health Care,United States
null
8220815
A view from the Agency for Health Care Policy and Research: the use of language in clinical practice guidelines.
"Good medicine is good law" is the first principle for writing good guidelines. The most important legal inquiry will be whether the language specifies mandatory or persuasive actions. Ordinary words may be hazardous when they are used ambiguously and create more than one meaning. That may mean a jury will decide what was meant.
Defensive Medicine,Health Policy,Health Services Research,Humans,Malpractice,Practice Guidelines as Topic,Psycholinguistics,Quality Assurance, Health Care,Semantics,United States
null
8220816
Assisting judges in screening medical practice guidelines for health care litigation.
In a far-reaching decision about scientific evidence in federal cases handed down at the very end of the 1992-1993 term, the U.S. Supreme Court implicated medical practice guidelines in indirect, profound, yet highly uncertain ways. In Daubert v Merrell Dow Pharmaceuticals, Inc the Court ruled that judges must actively screen novel scientific evidence to assure both its relevance and its reliability.
Expert Testimony,Humans,Interprofessional Relations,Malpractice,Practice Guidelines as Topic,Quality Assurance, Health Care,Terminology as Topic
1483656,1906073
8220817
A case study in progress: practice guidelines and the affirmative defense in Maine.
To encourage physicians to practice less defensively, the Maine Medical Liability Demonstration project adopted the controversial "affirmative defense" to combat runaway malpractice liability by granting immunity to physicians who follow practice guidelines. Despite challenges from trial lawyers, physicians are beginning to accept the program.
Defensive Medicine,Expert Testimony,Humans,Liability, Legal,Maine,Malpractice,Physician's Role,Practice Guidelines as Topic,Quality Assurance, Health Care
null
8220818
Ultrastructural study of glomerular basement membrane in diabetic rats by quick-freezing and deep-etching method.
The three-dimensional ultrastructure of glomerular basement membrane (GBM) in streptozotocin (STZ)-induced diabetic rats was examined by quick-freezing and deep-etching method. In three layers of the GBM of control rats, the outer and inner layers were formed by files of perpendicular fibrils, which connected the epithelial or endothelial cell surfaces with meshwork structures of the middle layer. In the diabetic rats, the inner layer was diffusely enlarged and the meshwork structure of the middle layer became markedly irregular due to the rupture of fine fibrils and thickening of material adherent to the fibrils. These ultrastructural changes correspond to those of subendothelial oedema, lamellation of lamina densa and fluffy material in the GBM, as revealed on conventional ultra-thin sections. It is suggested that the initial morphological change of STZ-induced diabetic nephropathy is disruption of matrix fibrils in the GBM, seemingly indicating a disturbance of size and/or charge barriers.
Animals,Basement Membrane,Diabetes Mellitus, Experimental,Diabetic Nephropathies,Freeze Etching,Kidney Glomerulus,Male,Rats,Rats, Wistar,Time Factors
130091,156660,690407,1864484,1899167,1900964,2038130,2051723,2332816,2384188,2591649,2670639,2681929,2755078,2784542,2835966,2948855,2993206,3172647,3352157,3410164,3533477,3536199,3550239,6086024,6400670,6480821,6545133,6893451,6981023,7132058
8220819
The effect of fibronectin on cytoskeleton structure and transepithelial resistance of alveolar type II cells in primary culture.
The cytoskeleton of alveolar type II cells on different matrices has been examined, and the bioelectric properties of these cells grown as monolayers in primary culture has be measured using Ussing-type chambers, to determine whether the extracellular matrix affects the cytoskeletal organization of alveolar type II cells and whether any such interactions influence their physiological functions. Alveolar type II cells cultured on a fibronectin substratum spread slowly over a 6-day period to produce cells of extremely large diameter. The cytoskeletal structure of these cells was characterized by a more marked accumulation of large bundles of actin and a finer network of keratin than cells grown on a collagen substratum. The transepithelial resistances of monolayers grown on a fibronectin substratum were much higher than those on a collagen substratum. These results indicate that alveolar type II cells cultured on fibronectin can form tighter, better organized and more polarized monolayers in primary culture, which suggests that fibronectin may have a physiologically important role in the maintenance of the alveolar wall.
Animals,Cells, Cultured,Cytoskeleton,Electric Impedance,Epithelium,Fibronectins,Pulmonary Alveoli,Rats,Rats, Sprague-Dawley
34631,2199285,2306374,2342331,2420188,2580120,2801919,3279816,3282243,3519680,3663713,3706898,3907445,4624331,6338785,6752288,6806307,6860655,6890416,7022020
8220820
Histochemical and biochemical determination of calcium in pleomorphic adenoma.
Although calcification seldom occurs in pleomorphic adenoma, it often occurs in salivary glands, and so we decided to investigate the possible role of calcium in this difference. A histochemical method using glyoxal bis(2-hydroxyanil) demonstrated a small amount of calcium outlining lumina and separated cells of epithelial structures and associated with cells of myxoid and chondroid regions in pleomorphic adenoma, and a conspicuous amount in the acini of the associated salivary glands. A biochemical method using dry ashing demonstrated a significantly higher level of calcium in the glands than in pleomorphic adenoma. The results indicate that the calcium is mainly associated with secretory granules, which are scarce in pleomorphic adenoma, and with proteoglycan present intercellularly and in stromal regions of pleomorphic adenoma. The calcium in secretory granules is of possible importance in calcification in lumina and epithelium, and that bound to proteoglycan is possibly released following necrosis to be of importance in stromal calcification. However, the overall low level of calcium in pleomorphic adenoma is the likely explanation for the usual lack of calcification.
Adenoma, Pleomorphic,Calcinosis,Calcium,Histocytochemistry,Humans,Salivary Gland Neoplasms
900499,1214193,1514938,1518646,1723726,2038778,2552653,2560368,2597019,6290430,6426150
8220821
In-situ polymerase chain reaction. An overview of methods, applications and limitations of a new molecular technique.
The in-situ polymerase chain reaction (in-situ PCR) is a novel molecular technique that combines the extreme sensitivity of the PCR with the anatomical localization provided by in-situ hybridization. A number of groups have recently reported studies using in-situ PCR for the detection of specifically amplified single-copy nucleic acid sequences in single cell preparations or low copy DNA sequences in tissue sections. In this overview, we describe the principles of in-situ PCR, review the applications of this technique and discuss future aspects of in-situ PCR. We critically compare the different in-situ PCR protocols described in the literature. Emphasis is placed on the absolute requirement for controls to allow accurate interpretation of results and the possible problems and pitfalls of the in-situ PCR methods, including artefacts related to diffusion of PCR products and non-specific incorporation of labelled nucleotides into fragmented DNA undergoing repair. It is concluded that this technique will eventually play an important role in specialized diagnostic laboratories in the evaluation of viral diseases, haematological and other malignancies which have unique genetic markers.
Artifacts,Humans,In Situ Hybridization,Polymerase Chain Reaction,Sensitivity and Specificity
1313061,1406887,1459861,1508667,1569974,1646989,1656763,1661072,1665538,1917036,2047872,2164214,8386712,8419941,8445483
8220822
Ultrastructure of human dermal mast cells in 29 different lysosomal storage diseases.
The effect of lysosomal storage diseases on the ultrastructure of human mast cells has not previously been reported. Indeed, there has been little published evidence indicating that mast cells contain typical lysosomes. However, mast cell cytoplasmic granules contain hydrolases similar to those found in lysosomes, but which differ from lysosomal hydrolases in exhibiting optimal activity at higher pH. We therefore examined by transmission electron microscopy the dermal mast cells in 58 biopsies of patients exhibiting 1 of 29 different lysosomal storage diseases. We found mast cells containing abnormal lysosomes in 16 of these disorders. In 6 of these 16 diseases, the mast cells' cytoplasmic granules appeared normal. These observations indicate that human mast cells can contain lysosomes, and provide evidence that the enzymes affected by lysosomal storage diseases are active in mast cells.
Biopsy,Cytoplasmic Granules,Humans,Lysosomal Storage Diseases,Lysosomes,Mast Cells,Retrospective Studies,Skin
426034,1127871,2431677,2473830,2673978,2806402,2892300,2964276,2972840,3275832,4363128,5322983,5431612,6230674,6240303,6322196,6397377,6530036,13928097
8220823
Role of fat-storing cells in schistosomal hepatic fibrosis of mice.
The involvement of fat-storing cells (FSC) in hepatic schistosomal granuloma was investigated in mice infected with Schistosoma mansoni cercariae. After infection, 24 animals were treated with s.c. injections of vitamin A in a total dose of 210,000 IU given twice a week for 3 weeks. Two other groups of 24 animals each were: a) non-infected vitamin A-treated animals and (b) untreated infected controls. Animals from all groups were killed at weekly intervals from the 5th through the 10th week following infection. Pieces of liver were examined by light microscopy and transmission electron microscopy. In all vitamin A-treated animals, FSC disclosed prominent cytoplasmic fat droplets, which permitted their prompt identification in the light and in the electron microscope. They were found in large numbers as a constituent of periovular granulomas. In infected controls, FSC were not identified in granulomas, possibly because lipid droplets disappeared during differentiation to the fibroblastic phenotype. FSC also appeared within areas of septal fibrosis. These data suggest that FSC play an important part in focal portohepatic fibrosis during granuloma formation around S. mansoni eggs in the liver of mice.
Adipocytes,Animals,Granuloma,Liver Diseases, Parasitic,Male,Mice,Schistosomiasis mansoni,Vitamin A
78498,1624540,1685276,1742208,2186487,2254460,2466750,2578584,2645938,2700593,2841439,3111965,3278941,3348774,3520661,3584927,3909149,3985121,4336540,5933819
8220824
Effects of hypercholesterolemia on initial and chronic phases of rat nephrotoxic serum nephritis: development of focal segmental glomerulosclerosis, analogous to atherosclerosis.
The effects of hypercholesterolemia on both the initial and chronic phases of rat nephrotoxic serum (NTS) nephritis have been investigated. Injury during the initial phase of NTS nephritis in hypercholesterolemic rats maintained on a cholesterol-supplemented diet (Group 2) was characterized by segmentally accentuated accumulations of vacuolated cells with lipid droplets (foam cells) in the glomeruli, while the kidneys of rats fed a standard diet (Group 1) revealed only mild intracapillary cell proliferation. Immunoelectron microscopy showed that the foam cells observed in Group 2 rats were largely derived from macrophages. The glomerular macrophage number, defined by the number of ED1-positive cells per glomerulus, was significantly higher in Group 2 than in Group 1 animals at days 5-6 (3.4 +/- 1.4 in Group 1 against 6.3 +/- 1.0 in Group 2; p < 0.01) as well as at days 21-28 (5.5 +/- 2.6 in Group 1 against 10.9 +/- 2.8 in Group 2; p < 0.01). In contrast, the numbers of OX19-positive T-lymphocytes and OX33-positive B-lymphocytes were similar in both groups. In the chronic phase of NTS nephritis at week 20, semiquantitative evaluation of the glomerular lesions disclosed more severe focal segmental glomerulosclerosis (FSGS) in Group 2 compared with Group 1 animals (glomerular injury score: 14 +/- 10 in Group 1 against 73 +/- 17 in Group 2; p < 0.01). Accumulations of lipid and foam cells were invariably seen in the sclerotic foci of Group 2 animals. The results indicate that hypercholesterolemia played an important role in the accelerated development of FSGS in rat NTS nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease,Animals,Arteriosclerosis,Cholesterol,Chronic Disease,Glomerulosclerosis, Focal Segmental,Hypercholesterolemia,Immunohistochemistry,Kidney Glomerulus,Male,Microscopy, Electron,Nephritis,Rats,Rats, Sprague-Dawley,Time Factors
127075,164779,1274579,1635356,1666992,1683060,1715446,1990206,2020653,2313977,2343305,2537019,2589483,2683576,2801885,2845810,2878525,2927082,3024493,3029503,3056028,3257650,3292816,3430956,3526558,3549534,3862110,3892159,3953770,5764874,6019573,6121416,6184518,6239058,6285662,6344647,6364825,6466191,6507587,6650664,6838694,14278226
8220825
[The fatty acid composition of the cellular structures of Yersinia pestis].
Fatty acid composition of lipopolysaccharides (LPS) and cytoplasmic membranes (CPM) of Yersinia pestis [correction of the plaque microbe] has been studied. Concentration of certain acids in the LPS content proved sharply different and thus the strains were separated into groups. High content of 3-oxymiristinic acid was a distinction of vaccine strains. Virulent strains of one of the groups regularly differed from the rest of virulent strains by high content of laurinic acid. Laurinic and two nonidentified acids, which were not found in the virulent cultures, were present in CMP lipids of vaccine strains.
Bacterial Vaccines,Chromatography, Gas,Cytoplasm,Fatty Acids,Intracellular Membranes,Lipopolysaccharides,Membrane Lipids,Virulence,Yersinia pestis
null
8220828
[The participation of the neuraminidase of Yersinia pestis in the transmission of the transmembrane signal].
Neuraminidase isolated from Yersinia pestis [correction of the plaque microbe] and purified has been studied for its effect on the peritoneal leukocytes of the white mice with results presented. Neuraminidase exerted the insulin-like effect on the peritoneal leukocytes of the white mice and this effect depended on the used dose. The priming of leukocytes by neuraminidase preparation was accompanied by the sharp increase of hydrogen peroxide production under effect of the capsule antigen of the plaque microbe and, apparently, by the appearance of additional binding sites for the adhesion piles of the plaque agent.
Animals,Carbon Radioisotopes,Escherichia coli,Insulin,Leukocytes,Luminescent Measurements,Membrane Potentials,Mice,Neuraminidase,Peritoneal Cavity,Signal Transduction,Yersinia pestis
null
8220827
[The resistance of the DNA of cyanophage LPP-3 to the action of different restriction endonucleases].
Data on the study of structure peculiarities of cyanophage LPP-3 DNA are presented in the work. The length of cyanophage DNA calculated by means of the enzymatic hydrolysis by restrictases is 40 +/- 3.5 thou. pairs of bases. Cyanophage LPP-3 DNA was hydrolysed by more than 50 different restrictases. As a result of screening it was found out that the great number of restrictases, which recognized hexanucleotide sequences did not hydrolyze DNA of cyanophage LPP-3. A considerable deviation of the number of the observed sites of restriction from their theoretically expected number for restrictases Hae III and Cfr 131 was established. Restrictases-isoschisomeres with different sensitivity to the methylation of the recognition sites--Msp I, Hpa II and Sau 3A, MboI and DpnI were used to check the availability of methylated bases in LPP-3 DNA. Absence of methylated adenine in the site GATC and methylated cytosine in the second position of the site CCGG were established. The results obtained permit supposing that the expressed counterselection by the sites of recognition of many restriction endonucleases takes place in cyanophage LPP-3 DNA. It is supposed that apparently, this method of protection of its genome in LPP-3 is one of most important but the inconsiderable percentage of site-specific methylation of the virus DNA cannot be completely excluded.
Bacteriophages,Base Sequence,Cyanobacteria,DNA Restriction Enzymes,DNA, Viral,Drug Resistance, Microbial,Electrophoresis, Agar Gel,Hydrolysis,Molecular Sequence Data,Phycodnaviridae,Restriction Mapping
null
8220826
[Soluble and semisoluble lectins from mollicutes and their possible functions].
When studying mollicute lectins it was established that Acholeplasma laidlawii PG-8 synthesizes two half-soluble lectins one of which is specific to N-acetyl-D-glucosamine, and the other--to D-glucosamine.HCl; phytopathogenic strain A. laidlawii var. granulum 118 produced 4 lectins one of which is soluble and specific in respect to fructose-1.6-diphosphate, the rest three lectins are half-soluble and specific to one of the sugars--D-galactosamine.HCl, rafinose and D-glucosamine.HCl. In Mycoplasma pneumoniae FH all the four lectins found in the culture liquid have been classified as half-soluble, specific to one of carbohydrates--D-galactosamine.HCl, talose, N-acetyl-neuramine acid and D-glucose; M. capricolum Cal. Kid. synthesizes four lectins; two of them being defined as soluble (one of the lectins is, respectively, specific to talose and D-glucosamine.HCl, two others, as half-soluble, specific to one of sugars--rafinose or D-glucose. The results obtained permit a conclusion to be made that the half-soluble lectins of mollicutes, on the one hand, are the factors of adhesion on the corresponding organs of macroorganism and, on the other hand take part in the transport of substances from without into the microorganism cell. Soluble lectins determine pathogenicity of mollicutes and form with half-soluble lectins a single chain to providing the mycoplasma cells with nutrients and to protect them from the action of the macroorganism immune system.
Acholeplasma laidlawii,Bacterial Adhesion,Culture Media,Lectins,Mycoplasma,Mycoplasma pneumoniae,Solubility,Tenericutes
null
8220831
[The pathogenicity factors in different representatives of the genus Citrobacter].
No trustworthy distinctions were revealed under the comparative analysis of properties of bacteria of Citrobacter genus from 3 studied ecological groups (from patients with diarrhea, from healthy persons and patients with extraenteric pathological process). It allows the finding of potentially partogenic bacteria of Citrobacter genus in patients with diarrhea to be considered the manifestation of dysbacteriosis.
Anti-Bacterial Agents,Bacterial Adhesion,Citrobacter,Diarrhea,Digestive System,Hemolysis,Humans,Microbial Sensitivity Tests,Time Factors
null
8220832
[The dynamics of the fungal mycelial content in the soils of stationary posts in a 30-kilometer zone around the Chernobyl Atomic Electric Power Station].
The paper deals with mycobiota of radionuclide-polluted soils of seven stationary posts in the 30-kilometer zone of the Chernobyl NPP and one in the vicinities of Kiev (Feofaniia). The lengths of light-and dark-coloured fungal mycelium were determined in the soil under study by the method of membrane filters for 1987-1989. Data obtained have been analyzed with the account of the radioactivity level of the soil samples, season and depth of the sampling horizon. The dynamics of mycelium content in soils has been traced which evidences for its seasonal changes and prevalence of dark-pigmented mycelium at the beginning which then was changed by predominance of light-coloured mycelium. It is supposed that radioactive contamination of soil is one of considerable components of the whole complex of ecological factors which determine the dynamics of fungal mycelium content in soil.
Accidents,Environmental Monitoring,Fungi,Nuclear Reactors,Power Plants,Seasons,Soil Microbiology,Soil Pollutants, Radioactive,Ukraine
null
8220829
[The body's nonspecific resistance factors in a localized experimental infection caused by Bacteroides].
Under local experimental infection induced by bacteroides of Fragilis group the factors of nonspecific organism resistance take an active part in the inflammation process. Phase changes of the state of monocytic-phagocytic and complement systems were observed. Peripheral blood leukocyte phagocytic activity decreased at the primary stage, then followed the complement activation by the alternative pathway mainly. The increase of phagocytic and metabolic activities of those phagocytes taking part in the inflammation, the complement at this stage is activated due to the classical pathway while being at the stage of clinic manifestation. Levels of antibody titres are also increasing.
Animals,Antibodies, Bacterial,Bacteroides Infections,Bacteroides fragilis,Complement Pathway, Alternative,Complement System Proteins,Disease Models, Animal,Histocytochemistry,Immunity, Innate,Leukocytes,Mice,Mice, Inbred C57BL,Phagocytosis,Time Factors
null
8220830
[The carriage of Staphylococcus aureus among different population groups].
The level of carriage of Staphylococcus aureus in three biotopes (nose, fauces, hand skin) and categories of carriers among students and teachers of the Medical Institute, medical personnel of surgical department and maternity hospital as well as the workers of combine building plant have been studied. The higher percentage of Staphylococcus aureus carriers was established in the nasal cavity of the maternity hospital personnel (p < 0.001) and on the hand skin of the personnel of surgical stationary (p < 0.05) as compared to the students and teachers. Carriage frequency of Staphylococcus aureus among the workers several times exceeded its level in the control group. The strains of the third phage group predominated among the personnel of surgical department, those of the second and fourth phage, groups, among the maternity hospital workers. Representatives of the second phage group were isolated in the plant workers. High level of carriage among the workers creates preconditions for the development of purulent diseases of the hand and fingers after microtraumas at the plant. All this dictates a necessity to eliminate Staphylococcus aureus in the carriers of all three biotopes.
Adolescent,Adult,Bacteriophage Typing,Carrier State,Engineering,Hand,Humans,Incidence,Medical Staff, Hospital,Middle Aged,Nose,Pharynx,Staphylococcal Infections,Staphylococcus aureus,Ukraine
null
8220833
[The current concepts of the mechanisms of the therapeutic-prophylactic action of probiotics from bacteria in the genus Bacillus].
Data from literature as well as the authors' experimental data on the mechanism of the effect of probiotics from aerobic sporeforming bacteria have been first generalized. The authors made a conclusion that the effect of biopreparations from bacilli is the multifactor process, when bacilli get to the gastrointestinal tract they begin producing biologically active substances which make the immediate effect on pathogenic and conditionally pathogenic microorganisms as well as activate specific and nonspecific systems of the macroorganism protection. The unknown before phenomenon of bacteria translocation is analyzed in detail as one of the most important factors of activation of non-specific resistance of the macroorganisms. Aerobic sporeforming bacteria produce a number of enzymes, amino acids, antibiotic substances and other biologically active substrates which add to the complex treatment-prophylactic effect of biopreparations from these bacteria. Prospects of the use of probiotics based on aerobic sporeforming bacteria in medicine and veterinary are considered. It is emphasized, in particular, that the potential multifactor character of the treatment-prophylactic efficiency of biological preparations from Bacillus is of positive value, since no negative effects are evoked by the known mechanisms of specific effect of aerobic sporeforming bacteria. This opens wide potentialities for improving the schemes and methods of application of probiotics from bacilli, creation of new forms of drugs on their base as well as to combine them with other preparations.
Animals,Antibiosis,Bacillus,Biological Factors,Biological Products,Humans,Immunity, Innate
null
8220837
Herpesvirus infections in childhood: 1.
Infections due to herpesviruses have received increasing attention over the past decade, culminating in the isolation in 1986 of human herpesvirus 6. We examine the clinical spectrum of acquired herpesvirus infections in children and review developments in our understanding of their molecular biology, pathogenesis, treatment and prevention.
Acyclovir,Administration, Oral,Child,Child, Preschool,Herpes Simplex,Humans,Infant,Infant, Newborn,Infusions, Intravenous,Prognosis,Viral Vaccines
195208,220797,1309395,1315930,1663650,1670839,1849612,1988829,1988830,2159613,2823137,2891886,3005858,3025727,3033092,3392410,3722509,3889872,6315977
8220840
Alcohol and depression.
Chronic alcohol misuse lowers mood and often leads to suicide or suicide attempts. yet drinking problems are often overlooked in patients presenting with depression, or the severity of mood change is unrecognized in a known alcohol misuser. Anxiety frequently accompanies problem drinking and accentuates depression. This article considers the implications for therapy.
Affect,Alcoholism,Antidepressive Agents,Anxiety Disorders,Comorbidity,Depressive Disorder,Humans,Medical History Taking,Psychotherapy,Suicide,Suicide, Attempted
321725,534813,1543943,1878077,2183544,2232018,2858246,2920070,3052036,3052668,3216643,3270510,3314963,3374135,3682826,4509758,4808436,4812974,5539859,5580368,5765626,6346922,6692076,7208740,13877834
8220838
Urinary urgency in women.
Urinary urgency is a common unpleasant symptom which may result from a variety of different pathologies. Careful patient assessment and appropriate investigation allow the cause to be elucidated and treated effectively in most cases. However, further research is necessary to increase our understanding of these disorders and to improve the quality of life of the women affected by them.
Causality,Cystitis,Cystoscopy,Female,Humans,Parasympatholytics,Quality of Life,Urinary Tract Infections,Urination Disorders,Urodynamics
753504,1988894,2005707,2039897,2207541,2442416,2486388,2669933,2769860,3368166,3401657,3599216,4084722,6139621,6191049,6360298,6428513,6805716,7032639,7049302,7359644,7401243
8220839
Antiphospholipid antibodies in pregnancy: clinical associations.
Antiphospholipid antibodies are a group of pathogenic antibodies associated with adverse pregnancy outcome. Pregnancies complicated by the presence of antibodies require careful surveillance and in specific situations therapy with low-dose aspirin, corticosteroids and/or heparin.
Adrenal Cortex Hormones,Antiphospholipid Syndrome,Aspirin,Clinical Protocols,Decision Trees,Drug Therapy, Combination,Female,Fetal Monitoring,Heparin,Humans,Pregnancy,Pregnancy Complications,Pregnancy Outcome,Prevalence,Thrombocytopenia,Thrombosis
472662,902839,1124664,1290429,1923159,1925655,1957844,1972484,2107479,2110431,2115735,2197866,2220676,2327456,2494618,2504043,2510616,2564148,2619675,2916633,3081022,3110418,3115237,3121871,3129519,3130772,3138989,3139464,3142262,3189362,3212387,3486073,3494845,3579340,3612644,3664156,3790464,3799744,3910324,3925336,3925759,3932854,3932855,3932856,3935364,6109901,6146787,6412932,6428168,7426535
8220841
First impressions.
'During a consultation there are two people at work. While the doctor is searching for a diagnosis, the patient is quietly summing up the doctor. And it is often the patient who reaches his conclusion first.' This quote from William Evans illustrates how the consultation involves a two-way analysis by both doctor and patient.
Attitude of Health Personnel,Attitude to Health,Clothing,Communication,Patient Satisfaction,Physician-Patient Relations,Referral and Consultation,Social Perception,Stereotyping,Surveys and Questionnaires
1747264,2508824
8220842
Management of acute asthma in childhood.
In children, acute asthma is one of the most common reasons for admission to hospital. Morbidity and mortality from asthma are unnecessarily high. It is essential that all those caring for asthma patients can accurately assess and treat an acute exacerbation of asthma.
Acute Disease,Asthma,Bronchodilator Agents,Child,Fluid Therapy,Humans,Medical History Taking,Oxygen Inhalation Therapy,Patient Admission,Patient Discharge,Peak Expiratory Flow Rate,Physical Examination
null
8220850
A peri-implant capsule flap.
Spherical expanders (30 ml) were implanted under the skin vascularised by the left inferior epigastric pedicle in rats. When expansion was complete, the expander was removed and the animals divided into three groups of 15. In the first group, the floor of the capsule was simply everted. In the second group, a capsule island flap was raised; in the third group, a capsule free flap was raised, transferred to the heterolateral vessels by microanastomosis; the inner side of the various capsule flaps was covered with autologous skin graft. In the three experimental groups, there was complete "take" of the skin grafts in 80% of the animals. Pedicle or free flaps of capsular tissue may be raised and transferred safely in rats.
Animals,Male,Prostheses and Implants,Rats,Rats, Wistar,Skin Transplantation,Surgical Flaps,Time Factors,Tissue Expansion Devices,Wound Healing
482435,792918,3301156,3608356,4705323,5132594,13419574
8220851
Surface ultrastructure of human dermis and wounds.
Scanning electron microscopic observations of the de-epidermalized surfaces of wounds and control skin reveal the architecture of dermal collagen. At wound edges there is a transition from the normal regular rete peg structure through erratically shaped finger-like projections with buds, to the relatively flat surface of granulation tissue. A corresponding change in the ultrastructure of dermal collagen is seen from normal areas where bundles of thick fibres are made up from finer fibrils, through a transitional zone where only fine fibrils are visible, to the granulation tissue where a disorganised amorphous structure is seen. It is suggested that the fibrous tissue surface at the edges of healing wounds is extensively remodelled after it is covered by epidermal cells.
Basement Membrane,Collagen,Fluorescent Antibody Technique,Granulation Tissue,Humans,Laminin,Microscopy, Electron, Scanning,Pressure Ulcer,Skin,Varicose Ulcer,Wounds and Injuries
1097542,1105199,2469857,2642514,3986642,4279800,6170832,6348179,7024426,14392240
8220852
The morbidity of the free vascularised fibula flap.
Twenty patients who had undergone free vascularised fibula flap transfers were reviewed to determine the incidence of peri and postoperative complications. The mean follow-up was 3.2 years (0.2-10); 18 grafts were successful, but required 10 re-operations for complications including 5 haematoma evacuations and 3 bone grafts and plates for delayed or non-union. The two unsuccessful fibula grafts required 11 re-operations, the majority for infections and non-union. Technical details of the operative procedure are reviewed for their part in the complications.
Adolescent,Adult,Anti-Bacterial Agents,Bone Screws,Bone Transplantation,Child,External Fixators,Female,Fibula,Fractures, Ununited,Graft Survival,Hematoma,Humans,Male,Middle Aged,Postoperative Complications,Reoperation,Surgical Wound Infection,Time Factors
365868,390575,1096183,1273122,2005141,2298771,2324134,2373557,2379352,2393767,2722923,2910611,2912628,3340672,3782218,4008020,6692051,18887289
8220853
The anatomic basis and clinical applications of flaps based on the posterior tibial vessels.
The vascular anatomy of the posterior tibial vessels has been studied in 20 legs of 10 cadavers. The number, size and distribution of the direct cutaneous and direct muscle branches of the posterior tibial vessels were recorded. For analysis, the leg was divided into four equal segments, Zone I being the most distal and Zone IV the most proximal. The direct cutaneous branches were found to cluster mainly around Zone II. The direct muscle branches to the soleus and flexor digitorum longus muscles arose chiefly in Zones II and III. Based on this knowledge, we performed fasciocutaneous, island soleus muscle, musculo-fasciocutaneous and flexor digitorum longus muscle flaps based on the posterior tibial vessels in 12 patients. Four were free fasciocutaneous flaps and eight were pedicled flaps. All flaps survived and there were no major complications. Delayed wound healing was encountered in three patients.
Adult,Aged,Aged, 80 and over,Fascia,Female,Fractures, Open,Humans,Leg,Male,Middle Aged,Muscles,Skin,Skin Transplantation,Surgical Flaps,Tibial Arteries
1090947,1314122,1410001,1623344,1946754,2178717,2293720,2353780,2367580,2804513,2862150,3567445,3730678,3898166,4011783,6739603
8220854
A distally based island first dorsal metatarsal artery flap for the coverage of a distal plantar defect.
An intractable plantar ulcer of the great toe was successfully covered with a distally based island first dorsal metatarsal artery flap. Common dorsal digital veins served as venous drainage for the flap. The results show that this flap can be used as a reliable alternative to conventional techniques to repair a distal foot defect.
Arteries,Foot,Foot Ulcer,Hallux,Humans,Male,Middle Aged,Nervous System Diseases,Surgical Flaps
1679684,2804512,2876797,6378037
8220855
Innervated reverse digital artery flap through bilateral neurorrhaphy for pulp defects.
To provide sensation to the reverse digital artery (RDA) flap, both the dorsal branch from the proper digital nerve and the superficial sensory branch from the corresponding radial or ulnar nerve are sectioned at their proximal ends and included with the RDA flap. These are then anastomosed with the distal ends of both radial and ulnar digital nerves at the recipient wound. Three cases of pulp defects reconstructed by this technique achieved very favourable functional and cosmetic results. The RDA flap, innervated through bilateral neurorrhaphy, seems to be an excellent option for one-stage reconstruction of major pulp defects.
Adolescent,Adult,Arteries,Child,Finger Injuries,Fingers,Humans,Male,Nerve Transfer,Skin,Skin Transplantation,Surgical Flaps,Suture Techniques
1393248,1401810,2299156,2350634,2665613,2673624,2673625,2746121,3349214,4609853,4920906,4946645,6353456,6622576,6725907,15417339,20277556
8220856
Neurocutaneous axial island flaps in the forearm: anatomical, experimental and preliminary clinical results.
The neurocutaneous island flap is an axial flap composed of one vein and one nerve, the arterial vascularisation of which is provided by the vascular plexus around and inside the nerve. The vascularisation of the lateral and medial cutaneous nerve of the forearm was studied in twenty fresh human upper limbs. In ten rats the vascularisation of these nerves was studied using latex injection and in twenty other animals neurocutaneous island flaps were raised based on the lateral forelimb cutaneous nerve and the medial cutaneous nerves of the forelimb. There was always a consistent arterial longitudinal plexus along the human and animal nerves, which linked the cutaneous perforating arteries. All the experimental flaps harvested survived well. On the basis of these anatomical and experimental findings neurocutaneous island flaps were raised on the forearms of three patients and are reported on.
Animals,Brachial Artery,Child,Cicatrix,Contracture,Elbow,Female,Forearm,Forelimb,Humans,Rats,Rats, Sprague-Dawley,Skin,Skin Transplantation,Surgical Flaps
1493530,1589854,1803548,2703673,3107143,4057168,4576708,6498385,6626821,7236984
8220857
Basal encephalocoele: imaging and exposing the hernia.
Basal encephalocoeles are rarely reported anomalies. Eight cases seen by one unit manifested external facial features and internal cerebral anomalies characteristic of the individual encephalocoele subgroups. CT and MR imaging delineates the anatomy of the skeletal defect and the associated cerebral abnormalities. Such imaging of cases of median cleft face syndrome may identify previously unsuspected basal encephalocoeles. Transcranial correction with increased exposure, if needed, by the technique of facial bipartition has been performed in five cases.
Child,Child, Preschool,Encephalocele,Humans,Infant,Infant, Newborn,Magnetic Resonance Imaging,Meningocele,Tomography, X-Ray Computed
717987,1700608,1901161,1999078,2080994,2661853,2909104,3259802,3335674,3698325,3762899,4966739,6069608
8220858
The galea frontalis myofascial flap in anterior fossa CSF leaks.
We report the clinical use of galea frontalis myofascial flaps in the treatment of anterior fossa cerebrospinal fluid leaks after trauma. This flap provides an adequately sized and vascularised barrier between the cranial and nasal cavities through which the cells of the inflammatory response reach the target area. This technique was used in 9 cases with complete success; in 5 out of 9 patients, repair of an anterior cranial base bone defect was also performed with split calvarial bone grafts, harvested from the frontal craniotomy bone. In all patients, neither recurrence of the CSF leakage nor postoperative meningitis or its recurrence were observed.
Adult,Cerebrospinal Fluid,Cerebrospinal Fluid Rhinorrhea,Ethmoid Bone,Fascia,Female,Frontal Bone,Humans,Male,Meningitis,Middle Aged,Muscles,Skull Fractures,Surgical Flaps
274502,377338,662948,3714887,4405895,5006640,5164219,5269338,5309641,5448746,5928632,6929863,7359973,7394047,13190185,13422116
8220859
The scapular fasciocutaneous flap: a new flap for reconstruction of the posterior neck.
The axial, myocutaneous and free flaps have made immediate reconstruction of head and neck defects possible. Notwithstanding this remarkable progress, defects of the posterior neck leave the reconstructive surgeon with very little choice. The scapular fasciocutaneous flap is easy to harvest, reliable and versatile, with functional and cosmetic results comparable to free flaps. We describe the anatomy and the technique of this new donor site, along with a case report.
Adult,Fascia,Female,Head and Neck Neoplasms,Humans,Neoplasm Recurrence, Local,Shoulder,Skin Transplantation,Surgical Flaps
372988,2584012,3567445,4932091,7066583,7071197
8220860
Early postoperative brachytherapy following free flap reconstruction.
Brachytherapy delivered within the early postoperative period has been associated with delayed wound healing and wound breakdown. The objective of this study was to determine whether reconstruction with a microvascular free flap reduced the incidence of wound breakdown in the presence of early postoperative brachytherapy following wide excision of soft tissue sarcomas and head and neck carcinomas. Ten patients with malignant tumours underwent wide excision and free flap reconstruction. Brachytherapy was administered using Iridium-192 wires in the early postoperative period via tubes inserted intra-operatively. In 9 of the 10 patients the wounds healed uneventfully, demonstrating that brachytherapy can be delivered in the early postoperative period following free flap reconstruction without an increase in the frequency of wound breakdown.
Adult,Aged,Aged, 80 and over,Brachytherapy,Combined Modality Therapy,Female,Head and Neck Neoplasms,Humans,Iridium Radioisotopes,Male,Middle Aged,Neoplasm Recurrence, Local,Postoperative Period,Sarcoma,Soft Tissue Neoplasms,Surgical Flaps,Time Factors
401617,414535,1122498,1157035,1309212,1895857,2662792,2742416,3102034,3337955,3975439,4705164,6186353,6692327,6693287,6693288,6821872,7272893,7379011
8220861
Early experience with the Lejour vertical scar reduction mammaplasty technique.
Over a 19-month period 25 bilateral reduction mammaplasties were performed using the Lejour technique. Results were assessed retrospectively. The mean follow-up was 12 months. The study showed that minor complications were common (40%), that nipple-areolar sensation was frequently reduced and that minor revision surgery for persistent dog-ears was often necessary (20%). Comparison with complications and revision rates in a similar group of patients who had undergone reduction mammaplasty using an inferior pedicle technique showed remarkably similar results. The positive findings of the current study were that nipple-areola necrosis was not encountered, patient satisfaction was high and the aesthetic results were generally good.
Adolescent,Adult,Cicatrix,Esthetics,Female,Humans,Lipectomy,Mammaplasty,Middle Aged,Patient Satisfaction,Postoperative Complications,Reoperation,Retrospective Studies
441191,539745,543656,831241,1712564,2782819,3602162,3630833,4011768,4551235,4567325,5339723,5464107,7031722,7208664,7352163,7447287,13335513,13724808,13835285,14072329
8220862
Bupivacaine and Kaltostat reduces post-operative donor site pain.
A prospective double blind controlled trial was carried out to examine the differences in post-operative split skin graft donor site pain between sites dressed with three differently treated types of dressing; a dry calcium alginate dressing (Kaltostat Britcair), a saline moistened Kaltostat dressing and a bupivacaine hydrochloride (0.5%) moistened Kaltostat dressing. There was a significant reduction in post-operative pain in the Kaltostat and bupivacaine group (group 3) at 24 and 48 h when compared to the other two groups (p < 0.04). There was no difference in ease of removal of dressings or the quality of wound healing on day 10 between the three groups. This study demonstrates a significant reduction in post-operative pain in bupivacaine soaked Kaltostat without reducing the beneficial effects of Kaltostat on donor site healing and we recommend its use in clinical practice.
Adult,Alginates,Bandages,Bupivacaine,Dermatologic Surgical Procedures,Double-Blind Method,Female,Glucuronic Acid,Hemostatics,Hexuronic Acids,Humans,Male,Middle Aged,Pain Measurement,Pain, Postoperative,Prospective Studies,Skin Transplantation,Sodium Chloride
1702958,2297102,2390548,2670027,3061354,3344486
8220863
Malignant melanoma excision margins: plastic surgery audit in Britain and Ireland, 1991, and a review.
In 1991, 146 consultant plastic surgeons in Britain and Ireland were sent a short questionnaire about their policies for excision margins for primary cutaneous malignant melanoma. 106/146 (73%) replied. 39/106 (37%) considered narrow margin (2-3 mm) excision biopsies adequate in certain cases. The minimum tumour thickness for a margin of more than 1 cm was 1 mm or more for 67/106 (63%) on the leg and for 57/106 (54%) on the back. The maximum margin was specified as 4 cm or more on the leg by 37/106 (35%) and on the back by 42/106 (40%). Other sub-groups of results were analysed. A review of the literature is presented.
Attitude of Health Personnel,Back,Female,Humans,Ireland,Leg,Male,Medical Audit,Melanoma,Skin Neoplasms,Surgery, Plastic,United Kingdom
69890,910211,1348807,1360100,1677695,1677705,1933198,2009058,2010179,2076865,2076866,2179292,2375644,2393768,3079582,3206240,3533204,3708278,3768643,3863575,3967194,3987915,3994259,4015217,4051107,4099805,5104886,5226822,5477666,5698493,5773814,6498388,6508406,6639164,6704906,6710291,6859994,7055381,7055382,7123480,7226105,7247529,7290125,7297594,7439222,8093791,12986673,13009650,13019089,13256269,13675981,13689716,14313180,14485771,14485772,14950651,15401132,17860107,18874402
8220864
Human orf.
Human Orf is an uncommon viral disease acquired through contact with infected sheep and goats. We report five cases of human Orf acquired while preparing mutton. The clinical picture and the management of human Orf are presented. Awareness of the benign nature of the condition is important in preventing ill-advised therapy.
Adult,Ecthyma, Contagious,Facial Dermatoses,Female,Hand Dermatoses,Humans,Male,Nose Diseases
1219046,1933121,3545022,3718854,4296716,6571964,7291348,14204699,14214186
8220865
Identical unusual subtotal penile amputation in children: a report of four cases.
4 cases are reported in whom an accidental or iatrogenic near complete slow amputation of the penis at the corona glandis was observed at first presentation. A representative case is presented in detail with illustrations showing the surgical repair carried out. The future erectile ability of this reconstructed phallus is speculated upon.
Amputation, Traumatic,Child,Child, Preschool,Humans,Male,Penile Diseases,Penile Erection,Penis
831352,1568110,3999207,4684983,7359460
8220866
Pressure developed under pressure garment.
To study how much pressure develops under a pressure garment, and how to obtain adequate effective pressure for scar treatment, we have used garments in combination with sponge and plastic plates in human volunteers. The pressures increased significantly when a sponge or sponge and plastic plate were used beneath the garment compared to pressures using a garment alone. In evaluations in patients with scar tissue on the limb, similar findings resulted.
Adolescent,Adult,Arm,Cicatrix,Evaluation Studies as Topic,Female,Forearm,Gravity Suits,Humans,Leg,Male,Middle Aged,Plastics,Pressure,Thigh
1003586,1493533,2104531,2205610,2757769,3319067,3707318,7241460,29265232
8220870
The effect of platelet-activating factor on the responsiveness of the human nasal airway.
1. The effects of inhaled platelet-activating factor (PAF) on responsiveness of the human nasal airway were examined in normal subjects by measuring nasal airway resistance in response to histamine and bradykinin at 2, 6, 24, 48 h and 7 d after PAF administration. Eosinophil cationic protein (ECP) in nasal secretions was also measured. 2. Intranasal aerosol administration of PAF, 30 or 60 micrograms per nostril to normal human subjects induced an increased responsiveness to inhaled histamine, 50 to 400 micrograms and bradykinin, 100 micrograms per nostril at 2, 6 and 24 h following PAF treatment. However the effect was not apparent at 48 h or 7 days after PAF administration. 3. Intranasal administration of lyso-PAF, 60 micrograms by aerosol did not increase the reactivity of the nasal airway in response to histamine, 200 micrograms. 4. There was no difference in the time course of the PAF-induced hyperresponsiveness to histamine or bradykinin. 5. PAF-induced nasal hyperresponsiveness at 2 and 6 h was associated with increases in the ECP concentration of the nasal lavage fluid. 6. Vitamin E pretreatment of subjects resulted in the attenuation of the PAF-induced hyperresponsiveness to histamine, and a decrease in ECP levels of the nasal lavage fluid. 7. The results suggest that in the human nasal airway, PAF induces a non-specific hyperresponsiveness which is accompanied by eosinophil activation in the nasal cavity. Free radical production induced by PAF may contribute to the hyperresponsiveness and the activation of eosinophils.
Administration, Inhalation,Adult,Airway Resistance,Blood Proteins,Bradykinin,Dose-Response Relationship, Drug,Eosinophil Granule Proteins,Free Radicals,Histamine,Humans,Nasal Cavity,Nasal Lavage Fluid,Platelet Activating Factor,Ribonucleases,Vitamin E
603764,948248,1467833,1596686,1793076,1878761,2131784,2155924,2282464,2328394,2333980,2447809,2669553,2849329,2873440,3005546,3010744,3084448,3181276,3322084,3345041,3514730,3977170,4144478,6354022,6370406,6470563,7346527
8220871
RS 23597-190: a potent and selective 5-HT4 receptor antagonist.
1. The pharmacological properties of RS 23597-190 (3-(piperdine-1-yl)-propyl-4-amino-5-chloro-2-methoxy benzoate hydrochloride) have been studied in vitro and in vivo. 2. RS 23597-190 competitively antagonized 5-HT4 receptor-mediated relaxations of rat, carbachol precontracted oesophageal muscularis mucosae, (pA2 = 7.8 +/- 0.1; Schild slope = 1.2 +/- 0.2). Affinity estimates (-log KB) at 5-HT4 receptors using either renzapride or SC-53116 as agonists yielded a -log KB value of 8.0 +/- 0.01. In contrast, RS 23597-190 failed to antagonize contractile responses to 5-HT of guinea-pig ileal 5-HT3 receptors, even at concentrations up to 10 microM. 3. Increases in short-circuit current, induced by 5-HT, were studied in guinea-pig ileal mucosal sheets. Concentration-response curves to 5-HT were biphasic, with the high potency phase to 5-HT inhibited by RS 23597-190 and mimicked by 5-methoxytryptamine. The -log KB value for RS 23597-190 at the high potency phase was 7.3 confirming that 5-HT4 receptors mediated the high potency phase. 4. In rat isolated vagus nerve, 5-HT elicited a slow, maintained depolarization at low concentrations and a rapid, transient depolarization at higher concentrations. The high potency, slow depolarizing phase to 5-HT was abolished selectively in the presence of 1 microM RS 23597-190 and the low potency phase was abolished selectively in the presence of 1 microM ondansetron. These data confirm that 5-HT4 and 5-HT3 receptors mediated slow and fast depolarization responses, respectively. 5. At 5-HT3 binding sites in membranes from NG 108-15 cells, labelled by [3H]-quipazine, RS 23597-190 exhibited an apparent affinity (- log Ki) of 5.7 +/- 0.1. At 5-HT3 receptors in membranes from rat cerebral cortex, labelled by [3H]-RS 42358-197, the apparent affinity (- log Ki) of RS 23597-190 was also 5.7 +/- 0.1. In both studies, Hill coefficients were not significantly different from unity. At 5-HT1A, 5-HT2,muscarinic M1, M2, M3, M4 and dopamine D1 and D2 receptors, RS 23597-190 exhibited low apparent affinities, with all - log Ki values less than 5.5.6. Intravenous infusion of RS 23597-190 in the conscious, restrained rat antagonized the von Bezold Jarisch reflex induced by 2-methyl 5-HT, with an ID50 of 300 microg kg-1 min-1, i.v. In the anaesthetized,bilaterally vagotomized micropig, RS 23597-190 (6 mg kg-1, i.v.) antagonized 5-HT-induced tachycardia with a half-life of 77 (63-99) min. Transient arrhythmic effects were noted after administration of the compound.7. In conclusion, RS 23597-190 acts as a high affinity, selective competitive antagonist at 5-HT4 receptors. Thus, the compound appears to be a useful tool for 5-HT4 receptor identification in vitro. In vivo, the compound is rapidly metabolized in pigs such that 5-HT4 blockade is not maintained. However,in the rat, when given by infusion, RS 23597-190 antagonizes 5-HT3 mediated responses, at doses consistent with a low affinity 5-HT3 receptor. These data suggest that, under appropriate experimental conditions, RS 23597-190 may also be used in vivo to characterize further 5-HT4 receptor function.
4-Aminobenzoic Acid,Aminobenzoates,Animals,Blood Pressure,Electrophysiology,Female,Guinea Pigs,Heart Rate,In Vitro Techniques,Intestinal Mucosa,Male,Metoclopramide,Muscle Contraction,Muscle Relaxation,Muscle, Smooth,Piperidines,Radioligand Assay,Rats,Reflex,Serotonin,Serotonin Antagonists,Swine,Swine, Miniature,Vagus Nerve,para-Aminobenzoates
1320204,1384896,1393286,1438521,1470221,1551411,1573641,1589907,1620231,1620241,1633936,1663456,1718042,1830236,1881455,2076474,2207493,2402303,2458457,2472554,3350057,3683864,3814920,3839291,4202581,5566763,6254391,8358562,8436978,8448587,13651579
8220872
Leukotriene D4- and prostaglandin F2 alpha-induced airflow obstruction and airway plasma exudation in guinea-pig: role of thromboxane and its receptor.
1. We studied the effects of a thromboxane A2 receptor (TP receptor) antagonist, ICI-192,605 (0.5 mg kg-1, i.v.) and a selective thromboxane (Tx) synthetase inhibitor, OKY-046 (30 mg kg-1, i.v.), on airway responses induced by leukotriene D4 (LTD4; 0.2 nmol) or prostaglandin F2 alpha (PGF2 alpha; 20 nmol) instilled via the airways route to anaesthetized guinea-pigs. For a comparison, airway responses to a TxA2-mimetic, U-46619 (0.02 nmol) were also studied. We measured both lung resistance (RL) to monitor airflow obstruction, and extravasation of Evans Blue dye to quantify airway plasma exudation. 2. Instilled LTD4 into the tracheal lumen induced an immediate peak and subsequently persistent increase in RL and produced a large amount of extravasation of Evans Blue dye at all airway levels. Both ICI-192,605 and OKY-046 significantly attenuated the persistent increase in RL following the immediate response and reduced LTD4-induced extravasation of Evans Blue dye in the trachea and proximal intrapulmonary airway. Instilled LTD4 produced significant increases in immunoreactive TxB2 in bronchoalveolar lavage fluid obtained 1.5 min after instillation of LTD4. 3. Instilled PGF2 alpha into the tracheal lumen induced an immediate increase in RL which peaked at approximately 15 s. We also observed a delayed sustained increase in RL, reaching a second peak at approximately 4 min. PGF2 alpha produced small but significant increases in the amount of Evans Blue dye at all airway levels. As with PGF2 alpha, instillation of U-46619 produced a biphasic increase in RL and extravasation of Evans Blue dye. The potency of PGF2a, in inducing these airway responses was about 1000 times less than U-46619. ICI-192,605 abolished both the immediate and the delayed increase in RL after PGF2a, and also blocked PGF2a,-induced extravasation of Evans Blue dye. However, OKY-046 had no inhibitory effects on these responses.4. We conclude that airflow obstruction and airway plasma exudation induced by instilled LTD4 is, in part, mediated via TxA2 generation and subsequent activation of TP-receptors. On the other hand,instilled PGF2a, while inducing similar responses, does so primarily by direct activation of TP receptors,rather than via TxA2 generation.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid,Airway Obstruction,Airway Resistance,Animals,Blood Pressure,Bronchoalveolar Lavage Fluid,Capillary Permeability,Dinoprost,Dioxanes,Evans Blue,Exudates and Transudates,Guinea Pigs,In Vitro Techniques,Leukotriene D4,Male,Methacrylates,Prostaglandin Endoperoxides, Synthetic,Receptors, Thromboxane,Thromboxane A2,Thromboxane-A Synthase,Vasoconstrictor Agents
124195,371730,1333740,1385805,1446142,1490516,1601835,1828386,1837014,1839139,2525122,2755146,2907537,3064106,3624684,6206700,6302738,6818617,6878731,6959812,8484619
8220873
Characterization of P2-purinoceptor mediated cyclic AMP formation in mouse C2C12 myotubes.
1. The formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and inositol(1,4,5)trisphosphate (Ins(1,4,5)P3), induced by ATP and other nucleotides was investigated in mouse C2C12 myotubes. 2. ATP (100 microM) and ATP gamma S (100 microM) caused a sustained increase in cyclic AMP content of the cells, reaching a maximum after 10 min. The cyclic AMP content reached a maximum in the presence of 100 microM ATP, followed by a decline at higher ATP concentrations. ATP-induced cyclic AMP formation was inhibited by the P2-purinoceptor antagonist, suramin. 3. Myotubes hydrolysed ATP to ADP at a rate of 9.7 +/- 1.0 nmol mg-1 protein min-1. However, further hydrolysis of ADP to AMP and adenosine was negligible. 4. The cyclic AMP formation induced by ADP (10 microM-1 mM) showed similar characteristics to that induced by ATP, but a less pronounced decline was observed than with ATP. ADP-induced cyclic AMP formation was blocked by suramin, while cyclic AMP formation elicited by adenosine (10 microM-1 mM) was insensitive to suramin. 5. The ATP analogue, alpha,beta-methylene-ATP also induced a suramin-sensitive cyclic AMP formation, while 2-methylthio-ATP and the pyrimidine, UTP, did not affect cyclic AMP levels. 6. Stimulation of the myotubes with ATP or UTP (10 microM-1 mM) caused a concentration-dependent increase in the Ins(1,4,5)P3 content of the cells. ADP (100 microM-1 mM) was less effective. Adenosine did not affect Ins(1,4,5)P3 levels. 7. Incubation of the cells with UTP (30 microM- 1 mM) inhibited the ATP- and ADP-induced cyclic AMP formation, suggesting that stimulation of the 'nucleotide' type P2-receptor inhibits P2-purinoceptor mediated cyclic AMP formation in C2C12 myotubes. In contrast, UTP (30 microM-I mM) enhanced adenosine-induced cyclic AMP formation.8. Adenosine-sensitive P1-purinoceptors activating cyclic AMP formation were found in C2C12 myotubes.Further, a novel P2-purinoceptor is postulated, sensitive to ATP, ADP and ATPgammaS, which also activates the formation of cyclic AMP in C2C12 myotubes.
Adenine Nucleotides,Adenosine Diphosphate,Adenosine Triphosphate,Animals,Cell Line,Cyclic AMP,Inosine Triphosphate,Mice,Microtubules,Muscles,Receptors, Purinergic P2,Stimulation, Chemical,Type C Phospholipases
166162,219375,563524,1330637,1335363,1393284,1474505,1687655,1700899,1846812,1846964,1883810,1972902,2063479,2291519,2420646,2430836,2433273,2443492,2456580,2554886,2560647,2806375,2819883,2841152,2875069,3029484,3033513,3161729,3359103,3498728,4330379,6244498,6248853,6302672
8220874
Partial inhibition by epithelium of tracheal smooth muscle relaxation induced by the potassium channel activator, BRL 38227.
1. A method is described whereby either the serosal (Out) or epithelial (In) sides of rat isolated tracheae were selectively perfused. Perfusion with BRL 38227 (10(-8)-5 x 10(-6) M; In/Out) of preparations with intact epithelium (+ EP) precontracted with carbachol (10(-6) M; Out/In) produced complete relaxation. Perfusion with aminophylline (10(-5)-10(-3) M; In) of + EP preparations precontracted with carbachol (10(-6) M; Out) also produced complete relaxation. 2. In preparations precontracted with carbachol (10(-6) M) epithelium removal (- EP) increased the sensitivity to the relaxant effect of BRL 38227 (In), but not BRL 38227 (Out) [- log EC50, + EP/- EP; carbachol (In), BRL 38227 (Out): 6.76 +/- 0.11 vs 6.67 +/- 0.15; carbachol (Out), BRL 38227 (In): 5.93 +/- 0.06 vs 6.25 +/- 0.07]. Removal of the epithelium increased also the sensitivity to BRL 38227 (In) of preparations precontracted with a lower concentration (5 x 10(-7) M) of carbachol (Out). [- log EC50, + EP/- EP, carbachol (Out), BRL 38227 (In): 6.19 +/- 0.14 vs 6.58 +/- 0.17]. 3. Removal of the epithelium did not affect the sensitivity to BRL 38227 (In) of preparations precontracted with a higher concentration (5 x 10(-6) M) of carbachol (Out). 4. In both + EP and - EP preparations precontracted with carbachol (10(-6) M; Out), BRL 38227 (In) had a more potent relaxant effect than aminophylline (In) (EC50, BRL 38227 vs aminophylline, + EP/- EP: 5.93 +/- 0.06 vs 3.66 +/- 0.11/6.25 +/- 0.07 vs 3.77 +/- 0.11). 5. In preparations precontracted with carbachol (10-6 M; Out), removal of the epithelium did not affect the sensitivity to aminophylline (In) but increased the degree of precontraction (Tmax) following epithelial but not serosal stimulation with carbachol.6. We conclude that BRL 38227, a K+ channel activator, is a potent relaxant of rat tracheal smooth muscle precontracted with carbachol, and that the effect can be partially inhibited by the presence of an intact tracheal epithelium, whereas the relaxant effect of aminophylline is not.
Aminophylline,Animals,Benzopyrans,Biotransformation,Bronchodilator Agents,Carbachol,Cromakalim,Epithelium,In Vitro Techniques,Male,Muscle Contraction,Muscle Relaxation,Muscle, Smooth,Potassium Channels,Pyrroles,Rats,Rats, Sprague-Dawley,Trachea
1188929,2108238,2123615,2172201,2184534,2448360,2606860,2819338,3006855,3057676,3207991,3310780,3664088,3994155,6317846,7174402
8220875
Kinetics of rate-dependent slowing of intraventricular conduction by the class Ib antiarrhythmic agent tocainide in vivo.
1. The effects of the class I antiarrhythmic agent, tocainide, on intraventricular conduction were assessed in guinea-pigs, anaesthetized with pentobarbitone sodium 60 mg kg-1, i.p. 2. After electrical ablation of the sinus node, heart rate was controlled by atrial pacing. His bundle electrograms were recorded by means of an epicardial bipolar electrode. 3. During continuous stimulation, comparison of HV intervals measured at a cycle length of 475 ms, with HV intervals measured at a cycle length of 250 ms yielded the following results: 25.26 +/- 0.64 ms versus 25.02 +/- 0.70 ms (NS), at baseline, 26.65 +/- 0.80 ms versus 29.88 +/- 1.13 ms (P < 0.001) after i.v. administration of 30 mg kg-1 tocainide, and 28.04 +/- 0.64 ms versus 36.24 +/- 1.31 ms (P < 0.001), after addition of 20 mg kg-1 tocainide. Thus, tocainide caused HV intervals to increase in a strictly rate-dependent fashion. 4. In order to characterize the rate-dependent class I activity of tocainide in terms of its binding kinetics to sodium channels, fractional sodium channel block was estimated from drug induced reductions of intraventricular conduction velocity (delta theta). On abruptly changing the drive cycle length from 500 ms to 250 ms, delta theta reached a new steady state with rate constants of 1.23 +/- 0.09 beat-1 and 1.28 +/- 0.09 beat-1, after administration of 30 mg kg-1 and addition of 20 mg kg-1 tocainide, respectively. At a basic drive cycle length of 250 ms delta theta recovered with time constants of 250.29 +/- 23.32 ms and 183.04 +/- 8.03 ms after administration of 30 mg kg-1 and addition of 20 mg kg-1 tocainide, respectively.5. The experimentally determined kinetic parameters were implemented into a mathematical model that assumes drug binding to sodium channels in terms of a periodical two-state process. Rate-dependent reductions in conduction velocity during continuous stimulation after administration of tocainide were closely approximated by steady state reductions in sodium channel availability as calculated on the basis of the aforementioned model.6. In agreement with previously published in vitro studies, our data, obtained in vivo, confirm the classification of tocainide as a class I antiarrhythmic agent with fast onset and offset kinetics. The kinetic parameters obtained in vivo can be used in order to predict steady state reductions in conduction velocity at a wide range of frequencies.
Animals,Anti-Arrhythmia Agents,Atrioventricular Node,Bundle of His,Cardiac Pacing, Artificial,Depression, Chemical,Electric Stimulation,Female,Guinea Pigs,Heart Conduction System,Heart Rate,Kinetics,Male,Models, Biological,Purkinje Fibers,Sodium Channels,Tocainide
334262,1253199,1291078,1317273,1317275,1333276,1381780,1498346,1514486,1653123,1694924,1717173,2426522,2441073,2467084,2510953,2542382,2707577,3936506,4254278,6331543,6444851,6652373,6777703,6883410,7379260
8220876
Regional haemodynamic effects of angiotensin II (3-8) in conscious rats.
1. It has been reported that angiotensin II (AII) (3-8) causes endothelium-dependent renal cortical vasodilatation, in anaesthetized rats, through interaction with a novel receptor that shows no affinity for the AT1-receptor antagonist, losartan. Therefore in order to get a fuller profile of the regional haemodynamic effects of AII (3-8) in conscious rats we assessed its renal, mesenteric and hindquarters vascular effects, and compared them to the responses elicited by AII and AIII. 2. AII and AIII (1.25, 12.5 and 125 pmol kg-1) caused dose-dependent pressor and renal and mesenteric vasoconstrictor effects. At doses up to 125 pmol kg-1, AII (3-8) was without any cardiovascular effects, but with doses of 1.25 and 12.5 nmol kg-1 there were dose-dependent increases in mean arterial blood pressure and reductions in renal and mesenteric flows and vascular conductances. The responses to AII (3-8) (12.5 nmol kg-1) were abolished by losartan (20 mumol kg-1). 3. Since it has been found that pretreatment with L-arginine can reveal a vasodilator effect of AII (3-8) on rabbit pial arterioles, we assessed responses to AII (3-8) (12.5 nmol kg-1) before and 5 min after onset of a primed infusion of L-arginine (1.4 mmol kg-1 bolus, 1.4 mmol kg-1 h-1 infusion). Responses to AII (3-8) were unchanged by L-arginine. 4. The results are consistent with AII (3-8) being a less effective agonist than All (or AIII) at the AT1-receptor, but provide no evidence for AII (3-8) interacting with a novel receptor that shows no affinity for losartan.
Amino Acid Sequence,Angiotensin II,Angiotensin III,Animals,Arginine,Biphenyl Compounds,Blood Pressure,Dose-Response Relationship, Drug,Heart Rate,Hemodynamics,Hindlimb,Imidazoles,In Vitro Techniques,Losartan,Male,Molecular Sequence Data,Rats,Regional Blood Flow,Renal Circulation,Splanchnic Circulation,Tetrazoles
1438983,1884112,1994182,2024289,2036715,2201207,3062060,3581810,6455924
8220877
Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones.
1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and, therefore, presumably additional mechanisms of analgesic action. Tramadol and its main metabolite O-desmethyltramadol were tested on rat central noradrenergic neurones of the nucleus locus coeruleus (LC), which are involved in the modulation of nociceptive afferent stimuli. 2. In pontine slices of the rat brain the spontaneous discharge of action potentials of LC cells was recorded extracellularly. (-)-Tramadol (0.1-100 microM), (+)-tramadol (0.1-100 microM), (-)-O-desmethyl-tramadol (0.1-100 microM) and (+)-O-desmethyltramadol (0.01-1 microM) inhibited the firing rate in a concentration-dependent manner. (+)-O-desmethyltramadol had the highest potency, while all other agonists were active at a similar range of concentrations. 3. (-)-Tramadol (10, 100 microM) was less inhibitory in brain slices of rats pretreated with reserpine (5 mg kg-1, 5 h before decapitation) than in controls. 4. The effect of (-)-tramadol (10 microM) was abolished in the presence of the alpha 2-adrenoceptor antagonist, rauwolscine (1 microM), whilst that of (+)-O-desmethyltramadol (0.3 microM) virtually disappeared in the presence of the opioid antagonist, naloxone (0.1 microM). (+)-Tramadol (30 microM) and (-)-O-desmethyl-tramadol (10 microM) became inactive only in the combined presence of naloxone (0.1 microM) and rauwolscine (1 microM). 5. In another series of experiments, the membrane potential of LC neurones was determined with intracellular microelectrodes. (-)-Tramadol (100 microM) inhibited the spontaneous firing and hyper-polarized the cells; this effect was abolished by rauwolscine (1 microM). (+)-O-desmethyltramadol (10 microM)had a similar but somewhat larger effect on the membrane potential than (-)-tramadol. The (+)-O-desmethyltramadol-(10 microM) induced hyperpolarization was abolished by naloxone (0.1 microM).6. The hyperpolarizing effect of noradrenaline (30 microM) was potentiated in the presence of (-)-tramadol(100 microM), but not in the presence of (+)-O-desmethyltramadol (10 microM). There was no potentiation of the noradrenaline (30 microM) effect, when the cells were hyperpolarized by current injection to an extent similar to that produced by (-)-tramadol (100 microM).7. Both noradrenaline (100 microM) and (- )-tramadol (100 microM) decreased the input resistance.8. The results confirm that the analgesic action of tramadol involves both opioid and non-opioid components. It appears that (-)-tramadol inhibits the uptake of noradrenaline and via a subsequent increase in the concentration of endogenous noradrenaline indirectly stimulates alpha2-adrenoceptors. (+)-0-desmethyltramadol seems to stimulate directly opioid micro-receptors. The effects of (+)-tramadol and(-)-O-desmethyltramadol consist of combined micro-opioid and alpha2-adrenergic components.
Action Potentials,Animals,Extracellular Space,In Vitro Techniques,Locus Coeruleus,Male,Membrane Potentials,Naloxone,Neurons,Norepinephrine,Rats,Rats, Wistar,Receptors, Adrenergic, alpha-2,Receptors, Opioid, mu,Stereoisomerism,Tramadol,Yohimbine
191143,228207,343791,415746,580215,843931,1309873,1596676,1813927,1982556,2171395,2342603,2411916,2573137,2579354,2825155,2849950,2852046,2908183,3317371,3625561,3653236,6092898,6110767,6120088,6141289,6278591,6308694,6493483,7198474,7384811,8467366
8220878
Use-dependent block of Na+ currents by mexiletine at the single channel level in guinea-pig ventricular myocytes.
1. The mechanism of use-dependent block of Na+ current by mexiletine was studied at the single channel level in guinea-pig ventricular myocytes by the patch-clamp techniques. All experiments were performed using stimulation protocols to enable us to analyze the strict dependence of changes in channel properties on channel use. 2. In cell-attached patches, bath or pipette application of mexiletine (40 microM) produced a use-dependent reduction of the peak average current without changes in single channel conductance. Null sweeps were increased and the number of openings per sweep decreased with successive pulses, whereas no significant change in the mean open time was detected during the train. 3. Block by mexiletine became greater when pulse duration was extended beyond the period in which channels were open, suggesting that block progressed without channel opening. 4. At near threshold potentials, mexiletine decreased the later occurrence of first openings. Additionally, late openings were reduced in a use-dependent way. 5. We conclude that mexiletine binds to the inactivated closed states of the Na+ channel and then causes a failure of late openings as well as early, which results in null sweeps on subsequent depolarization.
Animals,Electric Stimulation,Electrophysiology,Guinea Pigs,Heart,In Vitro Techniques,Mexiletine,Myocardium,Sodium Channels
300786,334262,378646,1645415,1663162,2154132,2157791,2411848,2411942,2414642,2415670,2439231,2441073,2448487,2457682,2458471,2536800,2539458,2548633,2553292,2555476,6203481,6270629,6274652,6281357,6310098,6316158,6331543,6620395,6652373,8383458
8220879
Evidence for participation of B1 and B2 kinin receptors in formalin-induced nociceptive response in the mouse.
1. This study was designed to investigate the role of bradykinin (BK), as well as the subtype of BK receptors involved, in formalin-induced hindpaw pain in the mouse by use of selective B1 and B2 receptor antagonists. In addition, we have analysed whether or not BK may be involved in formalin-induced hindpaw oedema in the mouse. 2. The pretreatment of animals with captopril (2 and 5 mg kg-1, s.c.) significantly increase the first and the second phases of formalin-induced pain. 3. Co-injection of the selective B1 receptor antagonist des-Arg9[Leu8]-BK (0.2-0.4 nmol/paw), together with formalin, caused graded and similar inhibitions of both phases of formalin-induced pain. Similar results were obtained with the B2 antagonists NPC 349 (D-Arg[Hyp3,Thi5,8-D-Phe7]-BK) and NPC 567 (D-Arg[Hyp3, D-Phe7]-BK) (0.2 and 0.6 nmol/paw). Higher concentrations of these antagonists (1 nmol/paw) failed to antagonize formalin-induced pain. 4. The new potent and selective B2 receptor antagonists, Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK), NPC 17731 (D-Arg[Hyp3, trans-4-propoxy-D-proline (transpropyl)7, Oic8]-BK), and NPC 17761 (D-Arg[Hyp3, trans-4-propoxy-D-proline (trans thiophenyl)7, Oic8]-BK) (0.02 to 1.0 nmol/paw), also caused significant inhibitions of both phases of formalin-induced pain. When Hoe 140 was injected subcutaneously 30 min before formalin injection (9.9 and 99 nmol kg-1), it significantly attenuated both phases of formalin-induced pain. The putative non-peptide BK antagonist, MV 8612 (1.6 to 9.6 nmol/paw), but not MV 8608 (5.5 to 33 nmol/paw), caused a graded inhibition of both phases of formalin induced pain, being, however, more active against the first phase.5. The pretreatment of animals with morphine (2.6 to 13 micromol kg-1, s.c.) caused dose-dependent and equipotent inhibitions of both phases of formalin-induced pain. In contrast, in domethacin (2.7 to 27 micromol kg-1) antagonized only the second phase of formalin-induced pain.6. The B2 receptor antagonists, Hoe 140, NPC 17731, NPC 17761, NPC 349 and NPC 567, all caused a significant inhibition of formalin-induced hindpaw oedema. A similar inhibition was also observed within domethacin but not with captopril or morphine.7. Our results provide strong evidence for the important role of endogenous BK, acting through both B1 and B2 receptors, in the genesis of both phases of formalin-induced persistent pain in the mouse. In addition, the current results also demonstrate that the inflammatory oedema associated with the later phase of formalin-induced pain seems to be mediated by endogenous BK, via activation of B2 receptors.
Animals,Binding, Competitive,Bradykinin,Bradykinin Receptor Antagonists,Captopril,Edema,Formaldehyde,Male,Mice,Morphine,Nociceptors,Pain Measurement,Receptors, Bradykinin
191908,564014,1174958,1318673,1364851,1383008,1408307,1425970,1652027,1711193,1771095,1848297,2015416,2043923,2064371,2158607,2247320,2429002,2478947,2537479,2545496,2896357,3207977,3221681,3289575,3543978,3594076,3614974,3656206,3714284,3952120,4033190,4041675,6132853,7015371,7060693,7108792
8220880
Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery.
1. We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately (7-mono-HR, 7,4'-di-HR, 7,3',4'-tri-HR, 5,7,3',4'-tetra-HR and 7,3'4'-tri HQ) upon the permeability of single perfused capillaries and venules in the mesenteries of pithed frogs. 2. In each experiment, the hydraulic permeability (Lp) of a single perfused microvessel and the effective osmotic pressure (sigma delta pi) exerted by macromolecules across its walls were estimated by a microcclusion technique, first during control perfusion and then in the presence of a known concentration of test substance. 3. HR, M and 7,4'-di-HR reduced Lp in a similar concentration-dependent manner over the range of 1 microgram ml-1 to 1 mg ml-1 (maximum reduction was to 40% of control Lp at 1 mg ml-1). At perfusate concentrations greater than 1 mg ml-1, these substances reduced Lp to a lesser extent. While the four other test substances reduced Lp significantly when their perfusate concentrations equalled or exceeded 100 micrograms ml-1, they were all less potent than 7,4'-di-HR. 4. The reduction in Lp induced by the mixture of flavonoids was only slightly reversed by subsequent perfusion with flavonoid-free solutions. 5. When permeability was increased by perfusing with protein-free solutions, both HR and 7,4'-di-HR reduced and then reversed the increase in Lp in a concentration-dependent manner over the range of 1 microgram ml-1 to 100 micrograms ml-1. None of the other component flavonoids was effective in restoring Lp under these conditions.
Animals,Blood Pressure,Capillary Permeability,Flavonoids,Hydroxyethylrutoside,In Vitro Techniques,Mesentery,Perfusion,Rana pipiens,Rana temporaria,Serum Albumin,Splanchnic Circulation
69248,301595,891587,1282862,1451724,1514607,1580094,1928406,2678805,2688186,2722410,2787181,3075669,3413125,3498831,3872988,3921691,4548540,5036407,5151308,6088413,6362258,6465329,6973022,7104791,7368843,7412590
8220881
Effects of L- and D-arginine and some related esters on the cytosolic mechanisms of alpha-thrombin-induced human platelet activation.
1. In Fura-2 preloaded human platelets, the increase in cytosolic calcium induced by alpha-thrombin was reduced by some L- and D-arginine ester compounds the IC50 (microM) values of which were 7.4 for TAEE, 56.9 for BAEE, 77.6 for TAME, 560 for T(d)AME, 656.3 for L-ArgOMe and 2206.7 for D-ArgOMe. alpha-tosyl-L-Arginine, L- and D-arginine were inactive. 2. The inhibitory activity of the L-arginine esters was not modified when platelets were pretreated with 100 microM N omega-monomethyl-L-arginine. 3. The L-arginine esters did not increase cyclic GMP content in platelets either in the presence or absence of indomethacin and apyrase at rest and after alpha-thrombin stimulation. 4. The kinetic parameters of platelet Na+/H+ antiporter (amiloride-inhibitable, evaluated after cytosolic nigericin-induced acidification) were modified by L- and D-arginine esters, while the native amino acids were ineffective. 5. The inhibitory effects of the L- and D-arginine esters on platelet activation appear to be mainly due to their inhibitory effect on Na+/H+ antiporter.
Adenosine Diphosphate,Apyrase,Arachidonic Acids,Arginine,Blood Platelets,Cyclic GMP,Cytosol,Humans,In Vitro Techniques,Indomethacin,Kinetics,Nitroprusside,Platelet Activation,Platelet Aggregation Inhibitors,Sodium-Hydrogen Exchangers,Spectrometry, Fluorescence,Stereoisomerism,Thrombin
656619,1672265,1695013,1701676,1852778,2102788,2166591,2175803,2243337,2245499,2282457,2328766,2366185,2432665,2539810,2550736,2575155,2826247,2827174,2831984,2835100,2838474,3027576,3094510,3166432,3311265,3395336,3495737,3653394,3787567,13771898,14236305
8220882
Electrophysiological effects of Org 7797 in the closed-chest anaesthetized dog.
1. The intravenous electrophysiological effects of a new antifibrillatory agent, Org 7797, were studied in closed chest anaesthetized dogs. Effects of fast sodium and slow calcium-mediated action potentials were also examined in guinea-pig isolated papillary muscle. 2. The major effects of a known antifibrillatory dose of Org 7797 (0.5 mg kg-1) were a protracted slowing of AV nodal conduction (for at least 20 min) and prolongation of the AV nodal functional refractory period. Conduction in the atria and His-Purkinje system (reflected by the St-A and HV intervals) were not significantly modified whilst ventricular conduction (reflected by the QRS interval) and the ventricular functional refractory period were only transiently prolonged. No other electrophysiological changes were seen. 3. A higher dose of Org 7797 (1.5 mg kg-1) slowed conduction at all levels of the myocardium (as evidenced by increases in the St-A, AH, HV and QRS intervals), slightly shortened cardiac repolarization (as assessed from JTc) and decreased Wenckebach rate. Atrial refractory periods were increased whereas effects on ventricular refractory periods were modest. 4. Neither heart rate nor sinus node recovery time were modified by either dose of Org 7797. 5. Org 7797, at a concentration (20 microM) which reduced Vmax of fast sodium-mediated action potentials in isolated papillary muscle by 83%, did not modify Vmax of slow calcium-mediated action potentials. It prolonged duration of the latter but did not modify that of the former. However, the plateau phase of both the 'fast' and especially the 'slow' action potentials was prolonged. 6. It is concluded that the main electrophysiological effects of a known antifibrillatory dose of Org 7797 in dogs with normal cardiac function are seen at the level of the AV node, actions which are unlikely to be explained by calcium channel block. Higher doses display a class Ic profile. This preferential action on the AV node may contribute to the control of ventricular rate during atrial fibrillation in the absence of infra-nodal conduction disturbances.7. These results contrast with those previously obtained in infarcted dogs and might further suggest that myocardial infarction enhances the Class I action of Org 7797.
Action Potentials,Anesthesia,Animals,Anti-Arrhythmia Agents,Atrioventricular Node,Dogs,Electrophysiology,Estrenes,Female,Guinea Pigs,Heart,Heart Conduction System,Heart Rate,In Vitro Techniques,Male,Myocardial Contraction,Papillary Muscles,Refractory Period, Electrophysiological,Sinoatrial Node
75367,94620,964279,1314031,1373273,1378126,1555619,1562117,1691395,1708044,1725906,1797309,1810599,1944606,2114236,2409789,2473403,2476592,2611495,2795468,3118399,3556176,3607364,3906318,4108657,6359849,6695682,6872170
8220883
Eicosanoid-dependence of responses of pre- but not postglomerular vessels to noradrenaline in rat isolated kidneys.
1. We investigated the role of nitric oxide (NO) and of vasoactive eicosanoids in the control of renal vascular resistance (RVR) and glomerular filtration rate (GFR) and of their responses to noradrenaline (NA). This study was conducted in single-pass perfused, isolated kidney preparations of the rat. 2. NA (63, 110 and 160 nM) dose-dependently increased RVR and to a lesser degree GFR. 3. In baseline conditions, N omega-nitro-L-arginine methylester (L-NAME, 100 microM) increased GFR more than RVR, thus demonstrating a basal release of NO which predominates in postglomerular vessels. 4. In kidneys stimulated with NA, L-NAME potentiated the increases in RVR but not in GFR. Indomethacin (1.5, 150 nM and 15 microM) did not alter GFR but markedly and dose-dependently reduced the NA-induced increase in RVR. Similar results were obtained with GR 32191B (10 and 100 microM), a prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist. 5. Indomethacin (15 microM) suppressed the enhancing effects of L-NAME on RVR responses to NA but did not affect those on GFR. 6. It is concluded that the mechanisms of the response to NA differ among pre- and postglomerular vessels. In preglomerular vessels the vasoconstrictor action and the NO release depend upon the activation of PGH2/TxA2 receptors, while both are eicosanoid-independent in the postglomerular vessels.
Animals,Biphenyl Compounds,Dinoprostone,Eicosanoids,Heptanoic Acids,In Vitro Techniques,Indomethacin,Kidney Glomerulus,Male,Nitric Oxide,Norepinephrine,Perfusion,Rats,Rats, Sprague-Dawley,Receptors, Prostaglandin,Renal Circulation,Thromboxane B2,Vascular Resistance
1282071,1313394,1345777,1472970,1552826,1592478,1592483,1618546,1725319,1731371,1733296,1999360,2000980,2045148,2072301,2115741,6157952,7194754,8418029
8220884
Estimation of partial agonist affinity by interaction with a full agonist: a direct operational model-fitting approach.
1. The operational model of agonism (Black & Leff, 1983) has been extended to describe the interaction between a partial agonist and a full agonist at the same receptor. The derived equation explicitly describes the interaction and allows the affinity (and efficacy) of the partial agonist to be estimated by direct fitting of raw experimental agonist concentration-effect (E/[A]) curve data. 2. The model was used to analyse experimental E/[A] curve data generated for the interaction between pilocarpine (partial agonist) and carbachol (full agonist) at the M3-muscarinic receptor mediating contraction of the guinea-pig isolated trachea. Pilocarpine affinity estimates obtained by operational model-fitting were compared with those obtained by use of the null method (Stephenson, 1956). These analyses demonstrated that the two methods gave comparable results (mean pKB estimates were 5.79 and 5.86 for the operational model and null method respectively). 3. When multiple concentrations of partial agonist are used, simultaneous operational model-fitting of all the E/[A] curve data allows the competitive nature of the interaction to be studied. 4. We conclude that operational model-fitting is a valid and analytically simple alternative to the conventional null method of analysing full/partial agonist interactions.
Animals,Binding, Competitive,Carbachol,Guinea Pigs,In Vitro Techniques,Male,Models, Biological,Muscle, Smooth,Parasympathomimetics,Phenoxybenzamine,Pilocarpine,Receptors, Cell Surface,Receptors, Muscarinic,Stimulation, Chemical,Trachea
978455,2329803,3978322,6055253,6121297,6141562,8220884,13383117
8220885
Pharmacological characterization of the novel nonpeptide angiotensin II receptor antagonist, BIBR 277.
1. The pharmacological profile of BIBR 277, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl ]- [1,1'-biphenyl]-2-carboxylic acid, a novel, nonpeptide angiotensin II receptor antagonist has been investigated by use of receptor binding studies, enzymatic assays, functional in vitro assays in rabbit aorta as well as in vivo experiments in pithed, anaesthetized and conscious rats. 2. BIBR 277 potently interacted with rat AT1 receptors (Ki 3.7 nM). Competitive receptor interaction was shown by radioligand saturation experiments performed in the presence of BIBR 277. The failure to inhibit radioligand binding to AT2 sites demonstrates the selectivity of BIBR 277 for AT1 receptors. This is further substantiated by the findings that BIBR 277 neither interacted with other receptor systems investigated nor affected the activity of components of the human renin-angiotensin system, such as plasma renin or serum converting enzyme. 3. In rabbit aorta, BIBR 277 had no agonistic properties and was shown to be an insurmountable antagonist of angiotensin II-induced contractions (KB 0.33 nM). The antagonistic effect persisted even after several wash-out procedures. However, this interaction was not irreversible since the insurmountable antagonism was concentration-dependently reversed when BIBR 277 (0.1 microM) and the surmountable antagonist, losartan (0.1 and 1.0 microM) were incubated simultaneously. The specificity of BIBR 277 for the AT1 receptor was further substantiated in this preparation since micromolar concentrations of BIBR 277 neither affected potassium chloride and noradrenaline-induced contractions nor acetylcholine-mediated tissue relaxation. 4. In pithed rats, i.v. administration of BIBR 277 (0.1, 0.3 and 1.0 mg kg-1) shifted the dose-pressor response curve to angiotensin II dose-dependently to the right with ED50 values of 0.23 microg kg-1 (control)and 1.4 microg kg-1, 4.7 microg kg-1 and 20 microg kg-1, respectively. As observed in the in vitro experiments no agonistic effect was detected and the maximum of the blood pressure response to angiotensin II at the highest dose of BIBR 277 was decreased by 29%.5. In anaesthetized rats, bolus i.v. administration of 0.1, 0.3 and 1.0 mg kg-1 BIBR 277 attenuated the blood pressure response to bolus i.v. injections of angiotensin 11 (0.1 microg kg-1). At the highest dose an almost complete blockade was observed even after 2 h.6. Single oral administration of BIBR 277 (0.3 and 1.0 mg kg-1) to conscious, chronically instrumented renovascular hypertensive rats dose-dependently decreased the mean arterial blood pressure by 15 and 30 mmHg, respectively. At the higher dose a significant antihypertensive effect was maintained for more than 24 h. Moreover, consecutive daily dosing of 1 mg kg-1 orally resulted in a sustained reduction in blood pressure over the 4 day observation period.7. It is concluded that BIBR 277 is an effective and selective angiotensin II antagonist with antihypertensive activity after oral administration.
Adrenal Medulla,Angiotensin II,Angiotensin Receptor Antagonists,Animals,Benzimidazoles,Benzoates,Blood Pressure,Decerebrate State,Dose-Response Relationship, Drug,Female,Humans,Hypertension, Renovascular,In Vitro Techniques,Lung,Male,Muscle Contraction,Muscle, Smooth, Vascular,Peptidyl-Dipeptidase A,Rabbits,Radioligand Assay,Rats,Rats, Wistar,Renin,Telmisartan
191856,762665,1393259,1467838,1587065,1614410,1625193,1855539,1918036,2022414,2072311,2159506,2179531,2179532,2213556,2313596,2485062,2485068,2590220,2775266,2827656,2858448,3032324,3280490,3326029,3551809,4202581,4331483,4401216,6083400,6154571,6305535,13651579,13662587,14907713
8220886
Centrally administered ouabain aggravates rapid-eye-movement-sleep-related bradyarrhythmias in freely moving rats.
1. The effects of continuous infusions of ouabain on bradyarrhythmias (cardiac pauses for 0.5 s or longer) during sleep were examined in freely moving Wistar-Kyoto rats. 2. In a control group (n = 7), saline was infused into both the lateral ventricle and the femoral vein. In an intracerebroventricular (i.c.v.) ouabain group (n = 7), ouabain was infused centrally, such that each rat received three stepped doses of 1, 10, and 100 ng kg-1 h-1 for 3 days at each dose, while saline was infused systemically. In an intravenous (i.v.) ouabain group (n = 7), ouabain was infused systemically at the same doses as the i.c.v. ouabain received, while the simultaneous i.c.v. infusion of saline was carried out. 3. Three-day i.c.v. infusions of the three stepped doses of ouabain caused a dose-dependent increase in the frequency of bradyarrhythmias during rapid-eye movement (REM) sleep without affecting the time spent in REM sleep, arterial pressure, average heart rate, or the frequency of bradyarrhythmias during non-REM sleep. Intravenous ouabain or i.c.v. saline had no effects on the frequency of bradyarrhythmias. 4. Intrinsic CNS activity during REM sleep may be involved in the centrally mediated arrhythmogenic properties of ouabain during sleep.
Animals,Bradycardia,Dose-Response Relationship, Drug,Electroencephalography,Injections, Intravenous,Injections, Intraventricular,Male,Ouabain,Polysomnography,Rats,Rats, Inbred WKY,Sleep Stages,Sleep, REM
43983,219481,655666,3731553,3781945,4257414,4351363,6484425,6846138,7250884
8220887
Effects of morphine metabolites on micturition in normal, unanaesthetized rats.
1. By means of continuous cystometry in normal, unanaesthetized rats, the effects on micturition of intrathecally (i.t.) administered morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), the two main metabolites of morphine, were studied and compared with those of i.t. morphine. 2. Both M6G (0.01, 0.1, and 0.5 microgram) and M3G (5 micrograms) were found to have significant effects on micturition. Like morphine (0.1, 0.5, and 10 micrograms), M6G was able to inhibit the micturition reflex, and produce urinary retention and dribbling incontinence in a dose-dependent manner. The potency of M6G for inhibiting micturition was approximately 10 times higher than that of morphine, and the duration of its effect was longer. All effects of M6G could be reversed by naloxone. 3. M3G (5 micrograms) facilitated the micturition reflex, resulting in decreases in bladder capacity and micturition volume, and an increase in spontaneous contractile activity. Pretreatment with naloxone (10 micrograms), which by itself had no effect on micturition, enhanced the facilitatory effects of M3G. In addition, M3G tended to counteract the inhibitory effects of both morphine and M6G on micturition. M3G (5 micrograms) also produced an excitatory behavioural syndrome. 4. It is concluded that in rats, i.t. M3G has excitatory effects on micturition and behaviour, probably not mediated via opioid receptors. I.t M6G has a potent inhibitory effect on micturition mediated by stimulation of opioid receptors. It may have effects on somatosensory afferent input in lower doses than those required for effects on micturition.
Animals,Behavior, Animal,Dose-Response Relationship, Drug,Female,Injections, Spinal,Morphine,Morphine Derivatives,Naloxone,Rats,Rats, Sprague-Dawley,Urinary Bladder,Urination
226219,1204496,1279654,1310249,1312161,1320685,1419474,1589243,2050192,2154808,2352759,2402182,2589681,2706485,2810109,2819776,2822899,2826951,2836207,2848167,2938524,2981312,2992671,3031278,3031640,3344988,3346833,3586176,3808084,3976321,4732523,4756170,5140097,6087220,6092610,6094211,6261872,6319664,6586255,6722535,6859567,6882627,7200737,7402440,8384276,8392118
8220888
The effects of ATP and alpha,beta-methylene-ATP on cytosolic Ca2+ level and force in rat isolated aorta.
1. The effects of a non-selective P2-receptor agonist ATP and a selective P2x-receptor agonist alpha,beta-methylene-ATP on intracellular free Ca2+ level ([Ca2+]i) and force were examined in rat isolated aorta without endothelium. 2. Both ATP (1-1000 microM) and alpha,beta-methylene-ATP (0.1-100 microM) induced transient increase followed by small sustained increase in [Ca2+]i in a concentration-dependent manner. Compared with the force induced by a high concentration of KCl, the force induced by alpha,beta-methylene-ATP was smaller and that induced by ATP was much smaller at a given [Ca2+]i. 3. An L-type Ca2+ channel blocker, verapamil (10 microM), completely inhibited the high K(+)-stimulated [Ca2+]i and force. Verapamil partially inhibited the transient and sustained increases in [Ca2+]i induced by 10 microM alpha,beta-methylene-ATP and the sustained increase but not the transient increase induced by 1 mM ATP. 4. In the absence of extracellular Ca2+ (with 0.5 mM EGTA) 1 mM ATP caused transient increase in [Ca2+]i while 10 microM alpha,beta-methylene-ATP was ineffective 5. ATP, but not alpha,beta-methylene-ATP, increased the tissue adenosine 3':5'-cyclic monophosphate (cyclic AMP) level. 6. These data suggest that ATP and alpha,beta-methylene-ATP increase [Ca2+]i by an activation of both L-type and non-L-type Ca2+ channels. In addition, ATP, but not alpha,beta-methylene-ATP, increases [Ca2+]i by a release of Ca2+ from an intracellular Ca2+ store. Possible reasons are discussed as to why the increase in [Ca2+]i due to ATP and alpha,beta-methylene-ATP resulted in only a small contraction.
Adenosine Triphosphate,Animals,Aorta, Thoracic,Calcium,Cyclic AMP,Cyclic GMP,Cytosol,Endothelium, Vascular,In Vitro Techniques,Male,Muscle, Smooth, Vascular,Rats,Rats, Wistar,Receptors, Purinergic P2,Verapamil
477720,1311958,1316981,1386189,1476162,1487116,1578367,1848549,1878749,1981306,2122973,2194223,2196860,2282460,2439921,2455792,2686129,2764093,2837603,2853158,2984001,2988672,2996968,3006665,3125371,3266079,3838314
8220889
Dissociation of the anti-ischaemic effects of cloricromene from its anti-platelet activity.
1. Cloricromene is a non-anticoagulant coumarin derivative with anti-platelet and anti-leukocyte properties, which has beneficial effects in various models of ischaemia and shock. 2. We have assessed the effects of cloricromene on (a) ex vivo platelet aggregation, and (b) infarct size using a model of myocardial ischaemia in the anaesthetized rabbit. 3. Cloricromene (1-1000 micrograms kg-1 min-1 for 15 min) induced a dose-dependent inhibition of ex vivo platelet aggregation, causing only a minimal increase in heart rate and no change in mean arterial blood pressure. The inhibitory activity was considerably stronger when platelet aggregation was induced by collagen than by ADP. 4. Cloricromene inhibited ex vivo platelet aggregation in rabbits pretreated with indomethacin (5 mg kg-1) and this inhibition persisted for 30-60 min. 5. The model of myocardial ischaemia involved 1 h occlusion of the first antero-lateral branch of the left coronary artery followed by 2 h of reperfusion. Infusion of cloricromene (30 or 300 micrograms kg-1 min-1), ibuprofen (80 micrograms kg-1 min-1) or vehicle began 15 min prior to occlusion, and continued throughout the experiment. 6. While area at risk was similar for all groups studied, cloricromene (30 or 300 micrograms kg-1 min-1) or ibuprofen caused a reduction in infarct size, and decreased myeloperoxidase activity in the tissue of the infarcted myocardium. 7. Cloricromene at 300 micrograms kg-1 min-1 also reduced the occlusion-induced elevation of the ST-segment of the rabbit electrocardiogram, and inhibited platelet aggregation ex vivo. Ibuprofen or cloricromene at 30 fg kg-1 min-1 had no effect on either the ST-elevation or platelet reactivity.8. Thus, cloricromene exhibits a cardioprotective activity via an inhibition of leukocyte infiltration, in the presence (300 microg kg-l min-1) or absence (30 microg kg-1 min-1) of inhibition of platelet activity ex vivo.The anti-aggregatory activity of cloricromene acts via a mechanism that is either different from, or in addition to, inhibition of cyclo-oxygenase, and is of long duration.
Animals,Blood Pressure,Chromonar,Coronary Vessels,Electrocardiography,Heart Rate,Ibuprofen,In Vitro Techniques,Indomethacin,Male,Muscle, Smooth, Vascular,Myocardial Infarction,Myocardial Ischemia,Myocardial Reperfusion Injury,Neutrophils,Peroxidase,Platelet Aggregation,Platelet Aggregation Inhibitors,Rabbits,Ventricular Pressure
684044,767019,1282601,1601052,1643242,1652342,1692444,1709231,2193049,2407376,2449815,2549432,2758223,2766481,3012375,3331949,3481402,3840290,5076276,6092199,6420544,6490209,6755493,6847789,7115470,7127687,7247911,7393988,13937023
8220890
A facilitatory effect of anti-angiotensin drugs on vagal bradycardia in the pithed rat and guinea-pig.
1. In pithed rats, preganglionic vagal nerve stimulation (at 5 Hz) elicited a bradycardia. This bradycardia was potentiated by the angiotensin converting enzyme inhibitor, captopril (1 mg kg-1, i.v.) by about 40%. Subsequent angiotensin II infusion (0.03 micrograms kg-1 min-1) reversed this effect. A similar facilitatory effect was also seen with the angiotensin receptor antagonist, losartan (10 mg kg-1, i.v.). These results suggest a tonic inhibitory effect of endogenous angiotensin II on vagal transmission. 2. The effect of captopril in potentiating vagal bradycardia appears to be at the level of vagal neurones, since the bradycardia elicited by the muscarinic agonist, methacholine was unaffected. 3. After the pithed rats were nephrectomized, captopril had no effect on vagally-induced bradycardia, suggesting that the formation of the endogenous angiotensin II responsible for the effect was dependent on renin release from the kidney. 4. When the sympathetic nerves of the pithed rat were electrically stimulated there was a tachycardia, and this was unaffected by captopril. However, when the sympathetic and vagus nerves were activated concurrently, the resulting tachycardia was inhibited by captopril. 5. In pithed guinea-pigs, captopril also potentiated the bradycardia caused by vagal nerve stimulation. This appears to be a tissue-selective effect since the bronchoconstriction due to the vagal stimulation was not affected by captopril. 6. These results suggest that endogenous angiotensin II can have a tonic inhibitory effect on cardiac vagal transmission. Disruption of this mechanism by anti-angiotensin drugs may attenuate the reflex tachycardia associated with the fall in blood pressure in anti-hypertensive therapy.
Angiotensin II,Angiotensin Receptor Antagonists,Angiotensin-Converting Enzyme Inhibitors,Animals,Biphenyl Compounds,Bronchoconstriction,Captopril,Decerebrate State,Electric Stimulation,Guinea Pigs,Heart,Heart Rate,Imidazoles,In Vitro Techniques,Losartan,Male,Methacholine Compounds,Nephrectomy,Rats,Rats, Sprague-Dawley,Sympathetic Nervous System,Tetrazoles,Tubocurarine,Vagus Nerve
14389,23967,183603,512963,656131,1655263,1697196,1854453,1854454,1979506,1984982,2213556,2478776,2565900,2590220,2642559,2692889,2856956,2984582,2994702,3064605,3066877,3129008,3218657,3880523,4249341,4312146,5275866,6176786,6188064,6209496,6323123,6354532,6358230,6478113,6758826,6958401,7011195,7074289,7192494,7397959
8220891
Characteristics of the bradykinin-induced changes in intracellular calcium ion concentration of single bovine tracheal smooth muscle cells.
1. Single bovine tracheal smooth muscle (BTSM) cells were cultured and used to measure bradykinin-induced changes in [Ca2+]i by dynamic video imaging. 2. Bradykinin (10 pM-10 microM)-induced an increase in [Ca2+]i over basal levels (69 +/- 2 nM; n = 353) which was concentration-dependent (log EC50 = -8.7 M) in the presence of extracellular calcium ions (2 mM). The bradykinin B2 receptor antagonist, D-Arg[Hyp3,Thi5,8,D-Phe7]- bradykinin, produced a parallel shift to the right of the bradykinin concentration-response curve (log EC50 = -7.1 M and -5.8 M in the presence of 1 microM and 10 microM antagonist respectively) yielding an apparent KD of 26 nM. 3. In the absence of extracellular calcium ions (with 0.1 mM EGTA), bradykinin (10 pM-10 microM) produced a uniform increase in [Ca2+]i from a basal level of 33 +/- 2 nM (n = 140) to approximately 180 nM in BTSM cells indicating an 'all-or-nothing' release of intracellular calcium ions. In the presence of 10 microM D-Arg[Hyp3,Thi5,8,D-Phe7]-bradykinin no responses could be induced by bradykinin at concentrations below 100 nM. However, at 100 nM and 1 microM bradykinin there was no change in the uniform increase in [Ca2+]i in these cells previously observed. 4. In both the absence or presence of D-Arg[Hyp3,Thi5,8,D-Phe7]-bradykinin, there was a concentration-dependent increase in the percentage of cells responding to bradykinin (frequency) under calcium-rich or calcium-free conditions. Individual cells also demonstrated a difference in the sensitivity to any particular concentration of bradykinin. 5. A latency in the response of cells to bradykinin was observed both in calcium-containing and calcium-free conditions.6. We conclude that bradykinin B2 receptors are expressed by BTSM cells and are involved in the bradykinin-induced increase in [Ca2+]i. It appears that the increase in [Ca2+], can be mediated via a graded influx of calcium ions from the extracellular space or an 'all-or-nothing' release from intracellular stores.
Adamantane,Animals,Bradykinin,Bradykinin Receptor Antagonists,Calcium,Cattle,Cells, Cultured,Image Processing, Computer-Assisted,Muscle, Smooth,Receptors, Bradykinin,Trachea
65285,686171,1330177,1432707,1649657,1663158,1691015,1697358,1848087,1898359,2017683,2169791,2185036,2221044,2310372,2439921,2452482,2546044,2550825,2783316,2906146,3540008,3838314,7015371,8220891
8220893
Functional evidence for multiple receptor activation by kappa-ligands in the inhibition of spinal nociceptive reflexes in the rat.
1. The evidence for kappa-receptor heterogeneity is equivocal. We have now investigated this question by comparing the effects of five putatively selective kappa-agonists. The parameters examined were: the relative potencies in depressing hindlimb flexor muscle reflexes to noxious pinch stimuli in both spinalized and sham-spinalized rats; the reversibility of these effects by naloxone; and the effects on blood pressure. 2. Two types of drug effect was discriminated. One drug group, represented by U-50,488, U-69,593 and PD-117,302, had a potency ratio between sham and spinalized rats approximately 10 fold lower than the other group, which comprised GR103545 and CI-977. 3. Under sham-spinalized conditions, CI-977 and GR103545 at high doses caused only sub-maximal reductions of spinal reflexes. U-50,488 was still active when superimposed on these high doses of GR103545. 4. Naloxone reversed all effects, but different doses were required between compounds, with GR103545 taking some 20 times higher doses of naloxone to cause reversal than did U-50,488. 5. The effects on mean arterial pressure were opposite between groups. 6. The results imply that more than one type of naloxone-sensitive non-mu opioid receptor must be involved in mediating these complex actions of ligands that have been claimed to be selective for kappa-receptors.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer,Analgesics,Animals,Anticonvulsants,Benzeneacetamides,Benzofurans,Blood Pressure,Decerebrate State,Male,Naloxone,Nociceptors,Piperazines,Pyrroles,Pyrrolidines,Rats,Rats, Wistar,Receptors, Opioid, kappa,Reflex,Spinal Cord,Thiophenes
1327387,1652344,1664760,1896211,1964823,2076476,2162533,2178014,2541524,2553920,2555011,2555012,2572992,2836010,2836012,2882399,2986999,2993510,3016446,6129321,6141484,6292616,6296719
8220894
Post-receptor pathway of the ATP-induced relaxation in smooth muscle of the mouse vas deferens.
1. The post-receptor pathway of the ATP relaxant effect in K(+)-precontracted vas deferens smooth muscle (VD) was examined. 2. The relaxation to ATP was not antagonized either by 10 microM methylene blue, a cyclic GMP inhibitor, by 10 microM indomethacin, an inhibitor of prostaglandin synthesis or by 100 microM NG-nitro-L-arginine, an inhibitor of NO production. 3. The Rp-diastereomer of adenosine 3':5'-cyclic monophosphorothioate (Rp-cAMPS) 200 microM, a competitive inhibitor of cyclic AMP significantly diminished the relaxant response to ATP. 4. Isoprenaline 10 microM, a beta-adrenoceptor agonist, produced a sustained relaxation, inhibited by Rp-cAMPS, without a significant change in [Ca2+]i, thereby mimicking the ATP-induced relaxant effect. 5. The level of the phosphorylated myosin light chain in the precontracted VD was significantly lowered by 1000 microM ATP. 6. ATP (1000 microM) and isoprenaline (10 microM) produced the same increase (+ 50%) of [cyclic AMP] when applied to a resting VD. 7. The effect of simultaneous increases of [Ca2+]i and of [cyclic AMP] produced by externally applied ATP are discussed. 8. These results suggest that ATP-induced relaxation in K(+)-precontracted VD is mediated by the activation of adenylyl cyclase.
Adenosine Triphosphate,Animals,Calcium,Cyclic AMP,Cytosol,In Vitro Techniques,Isoproterenol,Male,Mice,Muscle Contraction,Muscle Relaxation,Muscle, Smooth,Myosins,Phosphorylation,Potassium,Receptors, Purinergic P2,Vas Deferens
203858,213432,233257,387513,1317433,1338095,1467837,1504726,1593443,1677535,1981752,2043935,2155799,2156993,2164813,2173992,2194223,2196860,2234104,2328404,2388535,2438698,2459375,2547633,2551277,2838305,2842582,2849630,2983813,3216188,3816951,4351785,4400486,5284360,6112057,6142947,6265788,6895624,7117373,7202513
8220895
Evidence for sympathetic neurotransmission through presynaptic N-type calcium channels in human saphenous vein.
1. The specific type(s) of voltage-sensitive calcium channels (VSCCs) involved in sympathetic neurotransmission have not yet been characterized in human vascular tissues. We therefore examined the functional role of the N- and L-type VSCCs in human saphenous veins. 2. Contractile response curves for transmural nerve stimulation (TNS) and for exogenously administered noradrenaline (NA) were obtained in superfused saphenous vein rings. The contractions induced by TNS, but not by NA, were inhibited by 1 microM tetrodotoxin and by 10 microM guanethidine. Both responses were substantially reduced by 1 microM phentolamine, indicating that the contractions evoked by TNS were mediated by endogenous NA released from noradrenergic nerves. 3. In the presence of 2 microM omega-conotoxin GVIA (omega Conus Geographus toxin, fraction VI A; omega-CgTx), a polypeptide with specific inhibitory activity on N- and L-type calcium channels, the neurally evoked contractions were almost completely abolished. In contrast, the responses induced by exogenous NA were not affected by the neurotoxin, thus providing evidence of the exclusive presynaptic action of omega-CgTx. 4. In the presence of the calcium antagonist verapamil (10 microM), which selectively blocks L-type VSCCs, the contractions induced by both TNS and NA were diminished to the same extent, suggesting that the organic calcium blocker is active only at the postjunctional level. 5. It is concluded that N-type calcium channels are the main pathway of calcium entry controlling the functional responses induced by activating sympathetic nerves; the role of L-type channels appears to be limited to the postjunctional level, modulating smooth muscle contractions.
Adult,Calcium Channel Blockers,Calcium Channels,Electric Stimulation,Electrophysiology,Guanethidine,Humans,In Vitro Techniques,Male,Middle Aged,Muscle Contraction,Muscle, Smooth, Vascular,Norepinephrine,Peptides,Receptors, Presynaptic,Saphenous Vein,Sympathetic Nervous System,Synaptic Transmission,Tetrodotoxin,Verapamil,omega-Conotoxin GVIA
1654532,1660233,1671089,2164692,2172518,2372658,2409313,2410796,2432624,2432656,2438698,2447647,2451249,2456115,2458605,2460772,2469160,2547195,2568204,2570354,2865362,3601217,3723410,6468494,6509012

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