bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital nevi versus metastatic melanoma in a newborn to a mother with malignant melanoma – diagnosis supported by sex chromosome analysis and Imaging Mass Spectrometry
Authors: Alomari Ahmed K. , Glusac Earl J. , Choi Jennifer , Hui Pei , Seeley Erin H. , Caprioli Richard M. , Watsky Kalman L. , Urban Jennifer , Lazova Rossitza
Published: May 2015

A 37‐year‐old pregnant woman presented with a 2‐cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2‐mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm2 and no ulceration. Following induction of labor, the patient underwent re‐excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)‐based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario
Job Search Channels, Neighborhood Effects, and Wages Inequality in Developing Countries: The Colombian Case
Authors: Nicodemo Catia , García Gustavo Adolfo
Published: May 2015

This paper analyzes the relationship between social networks and the probability of finding a job. We explore geographic closeness as the social interaction to explain the job search function. Using data from Colombia in 2009, we calculate how neighborhoods have an effect on the channel used to find a job (social network versus no social network). In addition, we study how wage premium relates to using a social network in finding a job, exploring the inequality that can arise using a different job search method. Our results show that neighborhood affects the individual's job search method and that referred workers earn less at the bottom of the wage distribution with respect to non‐referred workers. Colombia presents persistent high levels of informality and inequality with the existence of spatial clusters that impose important social and economic costs with strong informational asymmetries on the job market.
Explaining the Productivity Growth Gap Between China and India: The Role of Structural Transformation
Authors: Liu Hehe , Yang Tianyu
Published: May 2015

Chinese and Indian aggregate productivity growth has been significantly different over the last 30 years. This paper studies the role of structural transformation in accounting for the aggregate productivity growth gap between two economies. We calibrate a neoclassical model of structural transformation for China and India. The model implies that higher productivity growth in China's manufacturing and agriculture accounts for most of the aggregate productivity growth gap between the two countries. According to the development strategy of China's government, China would start a new phase of structural transformation whereby employment is moving from manufacturing to services. Since the productivity growth gap in services is pretty small between China and India, if China wants to remain superior in relative productivity, it should improve the productivity growth rate of services. In contrast, the relative performance in India hinges on closing its productivity gap in agriculture and manufacturing relative to China.
Does food and fluid texture consumption relate to dietary intake in preschool children with cerebral palsy?
Authors: Gisel Erika
Published: May 2015

This commentary is on the original article by Benfer et al. on pages 1056–1063 of this issue.
Management of hyperosmolar hyperglycaemic state in adults with diabetes
Authors: Scott A. R. ,   the Joint British Diabetes Societies (JBDS) for Inpatient Care,   the JBDS hyperosmolar hyperglycaemic guidelines group
Published: May 2015

Hyperglycaemic hyperosmolar state (HHS) is a medical emergency, which differs from diabetic ketoacidosis (DKA) and requires a different approach. The present article summarizes the recent guidance on HHS that has been produced by the Joint British Diabetes Societies for Inpatient Care, available in full at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_HHS_Adults.pdf. HHS has a higher mortality rate than DKA and may be complicated by myocardial infarction, stroke, seizures, cerebral oedema and central pontine myelinolysis and there is some evidence that rapid changes in osmolality during treatment may be the precipitant of central pontine myelinolysis. Whilst DKA presents within hours of onset, HHS comes on over many days, and the dehydration and metabolic disturbances are more extreme. The key points in these HHS guidelines include: (1) monitoring of the response to treatment: (i) measure or calculate the serum osmolality regularly to monitor the response to treatment and (ii) aim to reduce osmolality by 3–8 mOsm/kg/h; (2) fluid and insulin administration: (i) use i.v. 0.9% sodium chloride solution as the principal fluid to restore circulating volume and reverse dehydration, (ii) fluid replacement alone will cause a fall in blood glucose (BG) level, (iii) withhold insulin until the BG level is no longer falling with i.v. fluids alone (unless ketonaemic), (iv) an initial rise in sodium level is expected and is not itself an indication for hypotonic fluids and (v) early use of insulin (before fluids) may be detrimental; and (3) delivery of care: (i) The diabetes specialist team should be involved as soon as possible and (ii) patients should be nursed in areas where staff are experienced in the management of HHS.
Nest boxes in planted and regrowth Forest Red‐gum (Eucalyptus tereticornis Sm.) ecosystems
Authors: Smith Geoffrey C. , Hogan Luke D. , Franks Alan , Franks Stacey
Published: May 2015

Nest boxes were deployed in planted and regrowth areas in association with a revegetation project to restore Forest Red‐gum (Eucalyptus tereticornis) ecosystems on abandoned former agricultural land. A year after revegetation began, 36 boxes were installed in each of the planted and regrowth areas in 2003, and these were monitored to 2013. Sixteen vertebrate species utilised boxes, which included breeding by four species and two species that were not detected by other survey methods. More boxes were used by fauna in the planting compared to regrowth in all but one audit. Significantly, more boxes were used by reptiles in regrowth than planting, but significantly more by birds in planting than regrowth. Nearly 90 per cent of boxes remained intact over the 10‐year period. While the study's capacity to attribute results to habitat types was limited, the results do add weight to the possibility that nest boxes made of good quality materials can provide valuable habitat for a wide range of species during the early recovery phase of reforestation projects.
Response of feral cats to a track‐based baiting programme using Eradicat® baits
Authors: Doherty Tim S. , Algar Dave
Published: May 2015

The feral Cat (Felis catus) is a significant threat to Australian fauna, and reducing their impacts is considered an essential action for threatened species conservation. Poison baiting is increasingly being used for the broad scale control of feral cats. In this study, we measured the population response of feral cats to a track‐based baiting programme using Eradicat® baits in the semi‐arid northern wheatbelt region of Western Australia. Over two years, 1500 baits were laid once annually and the response of feral cats was measured using remote cameras in a before–after, control–impact design. There was a significant reduction in feral cat activity in the second year, but not the first. During bait uptake trials, corvids removed the most number of baits, followed by cats and varanids. The lack of a response to baiting in the first year may be due to existing low cat numbers in the baited area and/or the timing of the baiting. We provide a list of key recommendations to help inform future cat baiting programmes and research.
Remotely‐sensed foliage cover and ground‐measured stand attributes are complimentary when estimating tree hollow abundances across relictual woodlands in agricultural landscapes
Authors: Ellis Murray V. , Taylor Jennifer E. , Rayner Laura
Published: May 2015

Hollows, also known as tree cavities, are critical to the survival of many animal species but are too poorly mapped across landscapes to allow for their adequate consideration in regional planning. Managing cost is important, so we tested whether freely available satellite‐derived foliage projective cover and field‐measured stand attributes could be used separately or combined to predict tree hollow abundance in relictual Australian temperate woodlands. Satellite‐derived foliage projective cover revealed variation in woody vegetation densities both within mapped woodland remnants and cleared areas of the agricultural matrix. Plot‐based field assessment of the actual number of hollows in each one‐hectare site (n = 110 sites) revealed a relationship with foliage cover. Improvement of the model was achieved if site‐based estimates of the proportion of the canopy due to Eucalyptus species and the number of mature trees per hectare were included. Remotely sensed foliage cover can improve on traditional vegetation mapping for predicting hollow‐bearing tree and hollow abundances at landscape scales when managing hollow‐dependent fauna habitat across relictual woodlands in temperate Australian agricultural landscapes. At finer scales, the addition of other predictors is necessary to raise the accuracy of the predicted hollow densities.
Comparing ecological restoration in South Africa and Western Australia: the benefits of a ‘travelling workshop’
Authors: Carrick Peter J. , Erickson Todd E. , Becker Carina H. , Mayence C. Ellery , Bourne Amanda R.
Published: May 2015

Researchers and practitioners of ecological restoration from South Africa and Western Australia recently undertook a travelling workshop across several South African biomes to discuss and evaluate the various approaches currently being utilised in the field. Key findings from the workshop highlighted the contrasting nature of ecological restoration undertaken in these two ecologically similar, but socially and politically different regions.
Virologically suppressed patients with asymptomatic and symptomatic HIV‐associated neurocognitive disorders do not display the same pattern of immune activation
Authors: Vassallo M , Durant J , Lebrun‐Frenay C , Fabre R , Ticchioni M , Andersen S , DeSalvador F , Harvey‐Langton A , Dunais B , Cohen‐Codar I , Montagne N , Cua E , Fredouille‐Heripret L , Laffon M , Cottalorda J , Dellamonica P , Pradier C
Published: May 2015

Objectives

Inversion of the CD4:CD8 ratio is a marker of immune activation and age‐associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV‐infected patients and explored differences according to clinical severity.

Methods

Post hoc analysis of data from two prospective cohorts of HIV‐infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV‐associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV‐associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded.

Results

Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/μL, the mean nadir CD4 count was 240 cells/μL, 27% were hepatitis C virus (HCV)‐coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty‐nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/μL [odds ratio (OR) 3.68] and with the presence of CD4+CD38+HLA+ cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level.

Conclusions

Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.
Global Survey of the Diagnostic Evaluation and Management of Cryptogenic Ischemic Stroke
Authors: Giruparajah Mohana , Bosch Jackie , Vanassche Thomas , Mattina Katie , Connolly Stuart J. , Pater Calin , Hart Robert G.
Published: May 2015

Background

About 25% of ischemic strokes are categorized as cryptogenic (i.e. of unknown cause), but few data exist about the extent of diagnostic testing or treatment. We undertook an international survey to characterize current diagnostic evaluation and antithrombotic management of patients with cryptogenic ischemic stroke in 2014.

Aims/Hypothesis

To determine the type of diagnostic evaluation undertaken for cryptogenic ischemic stroke and antithrombotic management and to compare across global regions.

Methods

An 18-question online survey was sent to 995 physicians involved in stroke care in 61 countries. Countries were separated into World Bank global regions and income groups. Diagnostic tests were considered routine if performed in >75% of patients at a center.

Results

Three hundred one completed surveys were received from 48 countries (response rate ∼30%). The majority (82%) of hospitals were from high-income countries and mainly from Europe and Central Asia (56%) and North America (19%). For ischemic stroke patients, magnetic resonance imaging is routinely obtained at 36% of hospitals (highest in North America, 58%). Among cryptogenic stroke patients, transesophageal echocardiography is routinely performed in 17% of hospitals. More than 24 hour cardiac rhythm monitoring is done routinely at relatively few (17%) hospitals (highest in North America, 33%). Intracranial arterial imaging is done routinely at 70% of hospitals, with no significant regional differences. Antiplatelet therapies are routinely prescribed for secondary prevention at 94% of hospitals.

Conclusions

Based on self-selected respondents from a large number of international stroke centers, transesophageal echocardiography and prolonged (>24 h) cardiac rhythm monitoring are not routinely performed in cryptogenic stroke patients, even in high-income countries. Antiplatelet therapy is the global standard for secondary prevention of cryptogenic stroke.
Performance status as a significant prognostic predictor in patients with urothelial carcinoma of the bladder who underwent radical cystectomy
Authors: Hinata Nobuyuki , Miyake Hideaki , Miyazaki Akira , Nishikawa Masatomo , Tei Hiromoto , Fujisawa Masato
Published: May 2015

Objectives

To assess the significance of performance status as a prognostic factor after radical cystectomy for urothelial carcinoma of the bladder.

Methods

The present study included 730 consecutive patients with urothelial carcinoma of the bladder who underwent radical cystectomy. Clinicopathological outcomes in these patients were analyzed focusing on the impact of performance status, which was assessed using the Karnofsky Performance Status scale before surgery. Patients were classified into groups with Karnofsky Performance Status ≥90 and ≤80.

Results

A total of 561 (76.8%) and 169 (23.2%) patients were judged to have Karnofsky Performance Status ≥90 and ≤80, respectively. During a mean of 52.0 months, disease recurrence and mortality occurred in 257 (35.2%) and 249 (34.1%) patients, respectively, and the 5‐year recurrence‐free and overall survival rates were 64.1 and 65.3%, respectively. There were significant differences in age, hemoglobin, albumin, estimated glomerular filtration rate, pathological T stage and nodal involvement between the Karnofsky Performance Status ≥90 and ≤80 groups. Multivariate analysis showed independent impacts of Karnofsky Performance Status, pathological T stage, nodal involvement and lymphovascular invasion on recurrence‐free survival, as well as independent impacts of Karnofsky Performance Status, age, body mass index, hemoglobin, pathological T stage, nodal involvement and lymphovascular invasion on overall survival.

Conclusions

The results suggest a significant association between impaired performance status and unfavorable prognosis in patients with urothelial carcinoma of the bladder undergoing radical cystectomy.
Rosai–Dorfman disease with atypical intrascrotal involvement
Authors: Rodríguez Torres Cristina , Riazuelo Fantova Gema , Escartín Martínez Irene , Castillo Escudero Juan José , del Agua Arias Celia
Published: May 2015

We describe two new cases of Rosai–Dorfman disease with intrascrotal involvement. Also known as sinus histiocytosis with massive lymphadenopathy, this is a rare entity, usually presenting with massive bilateral cervical lymphadenopathy. It is associated with extranodal involvement in up to 40% of cases, commonly in the face and neck area. Isolated intrascrotal involvement with no lymphadenopathies is extremely rare, and its definitive diagnosis is histopathological. Although they are the most frequent type, not all intrascrotal lesions are neoplastic; therefore, it is important to know other possible etiologies and their radiogical features that might help in the diagnosis. We also review other cases of intrascrotal involvement reported in the literature, as well as a review clinical features, treatment and prognosis of this entity, and a differential diagnosis of solid intrascrotal lesions.
Effect of long‐term phenothiazine treatment on drug metabolism.
Authors: Kolakowska T , Franklin M , Alapin B
Published: May 2015

1 The half‐life of plasma antipyrine was measured in twelve chronic schizophrenic patients during long‐term phenothiazine treatment and again following 4‐5 weeks on placebo. 2 The mean antipyrine half‐life was low during phenothiazine administration (6.1 +/‐ 4.2 h), rising after withdrawal of drugs to the range reported for untreated subjects by other authors (9.5 +/‐ 4.2 h). The prolongation of antipyrine half‐ life following the drug‐free period occurred in nine of twelve subjects and the difference was significant for the group at P less than 0.05. 3 The finding suggests that prolonged administration of phenothiazines stimulates the rate of drug metabolism.
Increased platelet aggregation responses to 5‐hydroxytryptamine in patients taking chlorpromazine.
Authors: Boullin DJ , Woods HF , Grimes RP , Grahame‐Smith DG
Published: May 2015

1 The aggregation response of platelets induced by 5‐HT was greatly increased in psychiatric patients receiving chlorpromazine therapy when compared with normal volunteers and psychiatric patients not receiving chlorpromazine. 2 Platelet aggregation responses to ADP were normal during chlorpromazine therapy, but 5‐HT induced aggregation was increased in rate and the typical transient reversible response was converted to an irreversible response in all subjects. This was usually indistinguishable from the ADP response. 3 When chlorpromazine therapy was stopped, plasma concentrations of chlorpromazine, monodesmethylchlorpromazine and chlorpromazine sulphoxide fell rapidly within one week, whereas 5‐HT induced platelet aggregation responses became normal after three weeks. The enhanced responses returned when chlorpromazine therapy was re‐instituted. 4 It is possible that platelet aggregation responses to 5‐HT in vitro could prove to be a useful index of the pharmacological effect of chlorpromazine in vivo.
Resuspension of platelets: enhanced 5‐hydroxytryptamine‐induced aggregation in chlorpromazine treated patients due to changes in platelet properties.
Authors: Boullin DJ , Grahame‐Smith DG , Grimes RP , Woods HF
Published: May 2015

1 Previous work showed that platelets from patients receiving chlorpromazine (CPZ) have an enhanced aggregation response to 5‐HT. This was caused by an action of CPZ on the platelets, a factor borne by the plasma, or both. 2 Therefore we studied 5‐HT induced aggregation of platelets from CPZ treated patients resuspended in normal plasma and from normal subjects resuspended in CPZ plasma. 3 Aggregation responses of normal platelets to 5‐HT were not enhanced by resuspension either in normal plasma or in CPZ plasma. In addition the enhanced responses of platelets from CPZ treated patients did not revert to normal after resuspension in normal plasma. 4 It is concluded that the enhanced aggregation response to 5‐HT seen after CPZ treatment is due to a change in the properties of the platelets rather than a factor in the plasma.
Changes in drug metabolism with increasing age: 2. phenytoin clearance and protein binding.
Authors: Hayes MJ , Langman MJ , Short AH
Published: May 2015

1 Comparison of phenytoin clearance showed a marked increase in people over 65 years of age compared with people under 45 years of age. 2 This difference was apparent if phenytoin was given orally or intravenously. 3 Phenytoin clearance correlated inversely with phenytoin binding and plasma albumin, both of which were found to be reduced in the elderly.
A comparison of the efficacy of cyclizine and perhenazine in reducing the emetic effects of morphine and pethidine.
Authors: Dundee JW , Loan WB , Morrison JD
Published: May 2015

1 The ability of cyclizine (50 mg) and perphenazine (2.5 and 5.0 mg) to counteract the emetic effects of pethidine (100 mg) and morphine (10 and 15 mg) was compared in women undergoing a standard minor operation with a standard anaesthetic. 2 Perphenazine (5.0 mg) was as effective an anti‐emetic as cyclizine (50 mg) and both were more effective than perphenazine (2.5 mg). 3 The reduction in vomiting and nausea by cyclizine (50 mg) and perphenazine (5 mg) was approximately the same following pethidine (100 mg) and morphine (10 mg) but much less against the larger dose of morphine. 4 Both anti‐emetics had a rapid onset of action but their anti‐emetic activity did not last as long as the emetic effect of morphine. 5 Perphenazine (5 mg) was accompanied by an unacceptably high incidence of restlessness. 6 In clinical practice cyclizine (50 mg) is preferred to perphenazine (5 mg) as an anti‐emetic.
Antagonism of reserpine‐induced emesis in pigeons: a screening method for antidepressant activity
Authors: DHAWAN K. N. , GUPTA G. P. , JAJU B. P.
Published: May 2015

Various antidepressant drugs and procedures have been studied against reserpine‐induced emesis in pigeons.

Electroconvulsions, pentylenetetrazol and a non‐hydrazide monoamine oxidase inhibitor (pargyline) block reserpine emesis.

It is suggested that reserpine‐induced emesis in pigeons provides a simple and reliable method for studying anti‐reserpine activity, and the compounds effective in antagonizing this emetic response are likely to have antidepressant property.
The effect of drugs on the constriction of isolated depolarized blood vessels in response to calcium or barium
Authors: NORTHOVER B. J.
Published: May 2015

The rat isolated anterior mesenteric artery was perfused at a constant rate with a calcium‐free depolarizing solution. Injection close to the cannula of 0.05–0.1 ml. of solutions of CaCl2(117 mm) or BaCl2(100 mm) caused a rise in perfusion pressure.

The responses to injected CaCl2solution could be obtained repeatedly but those to successive injections of BaCl2solution slowly declined. When the responsiveness to barium had almost disappeared, it could be restored by the addition to the perfusing fluid of a small amount of calcium (0.05 mm).

The contractile effects of calcium or barium were antagonized by the addition to the perfusing fluid of several anti‐inflammatory substances, certain local anaesthetics and certain spasmolytic drugs.

Perfusion of the mesenteric artery with a depolarizing solution containing 0.2 mm‐CaCl2caused a persistent rise of the perfusion pressure. This was rapidly and completely reversed by the addition of indomethacin (4 mg/100 ml.) or cinchocaine hydrochloride (2 mg/100 ml.) to the perfusing fluid.

The uptake of45Ca by rat aorta depleted of calcium was reduced by amethocaine hydrochloride (10 mg/100 ml.) or cinchocaine hydrochloride (2 mg/100 ml.) but not by indomethacin (10 mg/100 ml.) or desipramine hydrochloride (1 mg/100 ml.).
The influence of β‐adrenoceptive receptor blocking agents on urinary function in the rat
Authors: LEES P.
Published: May 2015

Intramuscular or subcutaneous injections of isoprenaline and dichloroisoprenaline and subcutaneous injection of pronethalol reduced the rates of excretion of water, sodium, potassium and chloride in the urine of conscious, hydrated rats. Inulin excretion usually fell at high, but not at low, dose levels. These changes were attributed to direct stimulant actions on β‐adrenoceptors in the kidney.

A reduction in perfusion pressure to the kidney may also have contributed to these urinary changes, because isoprenaline produced a transient fall in mean arterial blood pressure when given subcutaneously to anaesthetized rats.

Intramuscular injection of pronethalol and subcutaneous injection of antidiuretic hormone both reduced the rate of urine flow without modifying other parameters of urinary function (excretion of inulin and electrolytes were not diminished).

This latter action of pronethalol could not be ascribed to an increased secretion of antidiuretic hormone, for it also occurred in hypophysectomized rats.

Propranolol increased the renal excretion of sodium and chloride. A small rise in urinary potassium levels also occurred but urine volume and inulin excretion were not modified. Some possible modes of action of propranolol are discussed.
Assessment of the effectiveness of β‐adrenoceptor blocking agents towards cardiac and bronchiolar responses of the pithed guinea‐pig to electrical stimulation of the spinal outflow
Authors: BURDEN D. T. , PARKES M. W.
Published: May 2015

The responses of heart rate and resistance to lung inflation of the pithed guinea‐pig on electrical stimulation of the thoracic spinal roots could be related to similar responses to injected catecholamines, such that dose‐stimulus frequency relations could be plotted.

The range of frequency of stimulation that was equi‐effective with a dose range of injected catecholamines was higher for effects on air overflow than for heart rate. The slope of the relations for heart rate also differed from that for air overflow. These features may reflect a difference in effectiveness of the sympathetic innervation of heart and bronchial tree.

Propranolol was equally effective in reducing the responses of heart rate and air overflow to injected noradrenaline. Practolol was somewhat more active against the effects of noradrenaline on air overflow than on heart rate, though equally active against the effects of isoprenaline.

For the assessment of equivalent blockade of the effects of cord stimulation on heart rate and air overflow, frequency‐ratios corresponding to a noradrenaline dose‐ratio of 2 were derived from the slopes of the dose‐frequency relations; for air overflow this value was approximately 2 and for heart rate approximately 1·4.

When the doses required to produce these degrees of blockade were computed from the dose‐response relations for blockade of the effects of cord stimulation by propranolol, they were found to be similar for effects on heart rate and air overflow. For practolol, the effective dose for block of heart rate increase was found to be lower than that for air overflow.
A dual action of histamine on guinea‐pig lung vessels
Authors: OKPAKO D. T.
Published: May 2015

In isolated guinea‐pig lungs perfused through the pulmonary artery, histamine caused a rise in perfusion pressure which was converted to a fall by a prior injection of mepyramine.

Evidence is provided to show that at least part of the histamine effect was due to its direct action on pulmonary vascular tissue, and was largely independent of bronchomotor tone.

Neither the pressor nor the depressor effects were modified by adrenoceptor blocking agents, phentolamine and propranolol, in doses which reversed or blocked the effects of noradrenaline, adrenaline or isoprenaline. The actions of histamine could therefore not be attributed to catecholamine release. The involvement of cholinergic mechanisms was also excluded since atropine failed to influence the histamine effects.

It is suggested that the mepyramine‐sensitive pressor, and the mepyramine‐resistant depressor effects of histamine, were mediated by different receptors.

It is proposed that a vasodilator action of histamine leading to a partial obstruction of the pulmonary airways could be part of the explanation for the relative ineffectiveness of mepyramine in blocking anaphylactic bronchoconstriction in the guinea‐pig.
The anti‐inflammatory effect of catecholamines in the peritoneal cavity and hind paw of the mouse
Authors: GREEN K. L.
Published: May 2015

Carrageenin or 5‐hydroxytryptamine‐induced oedema of the mouse hind paw was antagonized by catecholamines acting on both α‐ and β‐adrenoceptors.

Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro‐inflammatory mediators was antagonized by catecholamines acting predominantly on β‐adrenoceptors.

The anti‐inflammatory effect of catecholamines was due neither to hyper‐glycaemia nor to the release of adrenal cortical hormones.
Occurrence of bombesin and alytesin in extracts of the skin of three European discoglossid frogs and pharmacological actions of bombesin on extravascular smooth muscle
Authors: ERSPAMER V. , ERSPAMER G. FALCONIERI , INSELVINI M. , NEGRI L.
Published: May 2015

Methanol extracts of the skin of Bombina bombina and Bombina variegata variegaia, two European discoglossid frogs, contain an active tetradecapeptide, bombesin. Alytesin, a tetradecapeptide strictly related to bombesin is present in extracts of the skin of Alytes obstetricans, another European discoglossid frog. The American frog Rana pipiens, contains in its skin ranatensin, an endecapeptide related to bombesin and alytesin.

Passage of crude skin extracts of Bombina through a column of alumina yields eluates which may be considered free of other peptide contaminants and are suitable for the isolation of bombesin in a pure form.

Bombesin has a stimulant action on several preparations of intestinal, uterine and urinary tract smooth muscle. Sometimes the effect is easily repeatable and shows a fair proportionality to the dose, but at other times a prompt and intense tachyphylaxis is observed. Other smooth muscle preparations are poorly sensitive or insensitive to bombesin. The rat uterus, the kitten small intestine, the guinea‐pig colon and the rat urinary bladder may be used for the quantitative bioassay of bombesin.

Bombesin‐like peptides may easily be distinguished from all other naturally occurring peptides by parallel assay. They constitute a new group of active peptides possessing a peculiar spectrum of activity.
Time course of acetylcholinesterase inhibition in the medulla oblongata of the rat by O‐ethyl S‐(2‐dimethylaminoethyl) methylphosphonothioate in vivo
Authors: BAJGAR J.
Published: May 2015

The time course of acetylcholinesterase inhibition in three parts of the medulla oblongata of the rat following intramuscular injection of O‐ethyl S‐(2‐dimethylaminoethyl) methylphosphonothioate was studied.

The inhibition in the three parts of the medulla oblongata proceeded at different rates and this indicates that penetration of the inhibitor through various parts of the blood‐brain barrier is not uniform.
EFFECT OF CLONIDINE ON THE EXCITABILITY OF VASOMOTOR LOCI IN THE CAT
Authors: DHAWAN B.N. , JOHRI M.B. , SINGH G.B. , SRIMAL R.C. , VISWESARAM D.
Published: May 2015

The effect of clonidine on the direct excitability of hypothalamic, medullary and spinal vasomotor loci has been investigated in cats anaesthetized with chloralose.

Clonidine inhibited the excitability of these loci when it was localized to the central sites by intracerebroventricular, intravertebral arterial or intrathecal injection in very low doses (1‐2 μg).

Topical application of clonidine (0.01% and 1.0%) to the floor of the fourth ventricle inhibited pressor responses evoked either by stimulation of medullary or hypothalamic vasomotor areas. Inhibition of the pressor responses was accompanied by hypotension and bradycardia in many experiments.

It appears that effects of clonidine on the vasomotor loci of the medulla oblongata and the spinal cord contribute to its hypotensive action.
CARDIOTONIC STEROIDS: CORRELATION OF SODIUM‐POTASSIUM ADENOSINE TRIPHOSPHATE INHIBITION AND ION TRANSPORT in vitro WITH INOTROPIC ACTIVITY AND TOXICITY IN DOGS
Authors: BEARD NICOL A. , ROUSE W. , SOMERVILLE A.R.
Published: May 2015

A new series of cardiotonics based on five steroid nuclei has been evaluated for inhibition of Na+/K+‐ATPase and Rb uptake by red blood cells, and for inotropic activity and toxicity in dogs. Structure‐activity relationships are discussed.

The in vitro tests can be used satisfactorily to predict inotropic activity, but not toxicity or therapeutic ratio.

Although compounds with greatly improved therapeutic ratios relative to ouabain and tolusin have been obtained, they proved to be strongly emetic in the conscious dog.
STUDIES ON THE POSITIVE INOTROPIC EFFECT OF PHENYLEPHRINE: A COMPARISON WITH ISOPRENALINE
Authors: LEDDA F. , MARCHETTI P. , MUGELLI A.
Published: May 2015

The effects of phenylephrine and isoprenaline on the isometric contraction of guinea‐pig ventricle were compared over the whole range of their respective dose‐response curves.

In preparations driven at 2.5 Hz the increase in contractile force induced by either isoprenaline or phenylephrine was linearly correlated to an increase in maximum velocity of force development. The relaxation time was shortened by isoprenaline but not by phenylephrine.

The negative inotropic effect induced by δ[N‐(3,4‐dimethoxyphenethyl)‐N‐methyl‐amino]‐α‐(3,4,5‐trimethoxyphenyl)α‐isopropylvaleronitrile hydrochloride (D600) was reversed by isoprenaline, but little influenced by phenylephrine.

The study of the interval‐force relationship shows that the increase in contractile force induced by phenylephrine (3 × 10−5 M) was relatively greater at low frequencies of stimulation, and that the maximum effect was reached at the frequency of 1 Hz.

The positive inotropic effect of phenylephrine (10−4 M) was significantly higher at a frequency of 1 Hz than at 2.5 Hz; the effect of isoprenaline (3 × 10−8 M) was not significantly different at the two driving frequencies.

In preparations driven at 1 Hz the inotropic effect of the lower concentrations of phenylephrine was due to an increase in the time to peak tension without any change of the maximum velocity of force development; however an increase of this parameter became evident only after higher concentrations of the amine (10−5 M or more), associated with a progressive shortening of the time to peak.

A correlation between mechanical and electro physiological effects of phenylephrine is attempted; the suggestion is advanced that the prolongation of the action potential and of the active state duration may be an important factor in the inotropic effect of phenylephrine.
STUDIES ON THE BEHAVIOURAL PHARMACOLOGY OF A CYCLIC ANALOGUE OF DOPAMINE FOLLOWING ITS INJECTION INTO THE BRAINS OF CONSCIOUS RATS
Authors: ELKHAWAD A.O. , WOODRUFF G.N.
Published: May 2015

The cyclic analogue of dopamine, 2‐amino‐6,7‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene (ADTN) was injected into the lateral ventricle or bilaterally into the nucleus accumbens or caudate nucleus of conscious rats and its effect on locomotor activity was investigated.

When given intraventricularly, ADTN produced some stereotyped responses which were followed by a strong and long lasting stimulation of locomotor activity. When administered bilaterally into the nucleus accumbens a similar stimulation of locomotor activity was observed. ADTN had no effect on locomotor activity when injected bilaterally into the caudate nucleus.

The ADTN‐induced locomotor stimulation following its intraventricular injection was completely abolished by a low dose of pimozide (0.01 mg/kg, i.p.) or haloperidol (0.5 mg/kg, i.p.). Pimozide (1 mg/kg, i.p.) given 30 min before ADTN injected bilaterally into the nucleus accumbens completely blocked locomotor stimulation.

Unilateral injections of ADTN (5 μg) into the nucleus accumbens caused locomotor stimulation but no turning.

Bilateral injections into the nucleus accumbens of 2‐amino‐6,7‐dimethoxy‐1,2,3,4‐tetrahydronaphthalene or 0.9% w/v NaCl solution had no effect on locomotor activity.

It is concluded that the central stimulant action of ADTN is due to an effect on the dopamine receptors in the nucleus accumbens.
MECHANISM OF ACTION OF DOPAMINE ON THE GUINEA‐PIG GASTRO‐OESOPHAGEAL JUNCTION in vitro
Authors: COX BARRY , ENNIS CHRISTINE
Published: May 2015

The effect of dopamine on longitudinal muscle strips of the guinea‐pig isolated gastro‐oesophageal junction was compared with the response obtained to phenylephrine, isoprenaline and clonidine. Phenylephrine (5 × 10−7 to 5 × 10−5 m) produced a dose‐related contraction, whilst dopamine (10−6 to 10−4 m) and isoprenaline (5 × 10−7 to 2 × 10−5 m) produced dose‐related relaxations. Clonidine was ineffective in doses up to 10−5 m. 5‐Hydroxytryptamine (5‐HT) produced a contraction.

Phenylephrine was antagonized by α1‐adrenoceptor antagonists but unaffected by β‐adrenoceptor antagonists, whilst the opposite was the case for isoprenaline. A mixture of α‐ and β‐adrenoceptor antagonists was required to inhibit completely dopamine‐induced relaxations. 5‐HT (3 × 10−7 m) was specifically antagonized by methysergide (3 × 10−6 m).

pA2 values for a range of α‐adrenoceptor and dopamine receptor antagonists were determined against dopamine and phenylephrine. The relative order of potency of the antagonists was the same for both antagonists and was prazosin > spiroperidol > phentolamine > domperidone > haloperidol, with pimozide and metoclopramide being inactive.

Tyramine caused dose‐related relaxations of the gastro‐oesophageal strips which were susceptible to the same range of antagonists as dopamine.

Cocaine (6 × 10−6 m) and desmethylimipramine (3 × 10−7 and 10−6 m) reduced the relaxations induced by dopamine and tyramine but there were quantitative differences in the antagonism.

Tissue from reserpine pretreated guinea‐pigs was insensitive to tyramine but the response to dopamine was only partly reduced.

Histological examination of the strips revealed the presence of smooth muscle but only a sparse adrenergic innervation.

The results suggest that dopamine acts partly indirectly and partly directly on postjunctional α‐and β‐adrenoceptors. There is no evidence for an action on specific dopamine receptors.
THE OCCURRENCE OF POSTSYNAPTIC α‐ AND β‐ADRENOCEPTORS IN THE GUINEA‐PIG GALL BLADDER
Authors: DOGGRELL SHEILA A. , SCOTT G.W.
Published: May 2015

Guinea‐pig gall bladder strips were contracted by (–)‐noradrenaline, 10−5 m, and by field stimulation at 5 Hz (in the absence or presence of 10−6 m atropine) and relaxed to 10−5 m (–)‐isoprenaline. (–)‐Adrenaline, 10−5 m, predominantly contracted, but sometimes relaxed, this preparation.

In the presence of 10−6 m phentolamine, contractions to (–)‐noradrenaline and to (–)‐adrenaline were reversed to relaxations. The relaxations produced by (–)‐isoprenaline were unaltered. In the presence of 10−6 m propranolol, contractions to (–)‐noradrenaline increased in magnitude, relaxations to (–)‐adrenaline were reversed to contractions, and relaxations to (–)‐isoprenaline were abolished. These results demonstrate the presence of postsynaptic α‐adrenoceptors which mediate contractions, and postsynaptic β‐adrenoceptors which initiate relaxations, in the guinea‐pig gall bladder.

The contractile responses to continuous field stimulation for 5 min at 5 Hz in Krebs solution alone were reduced in magnitude by propranolol, 10−6 m. In the presence of 10−6 m atropine (added to eliminate the cholinergic component of the response), propranolol, 10−6 m, had no effect on responses to stimulation at 5 Hz. Thus propranolol reduced the response to cholinergic stimulation in this tissue; the basis of this effect is unclear. In the absence or presence or atropine (10−6 m), the responses to 5 Hz were smaller in magnitude in the presence than absence of phentolamine, 10−6 m. This suggests that the responses to field stimulation of the guinea‐pig gall bladder may, in part, be due to the release of endogenous noradrenaline which acts at postsynaptic α‐adrenoceptors.
ACTION OF ENKEPHALIN ANALOGUES AND MORPHINE ON BRAIN ACETYLCHOLINE RELEASE: DIFFERENTIAL REVERSAL BY NALOXONE AND AN OPIATE PENTAPEPTIDE
Authors: JHAMANDAS KHEM , SUTAK MAAJA
Published: May 2015

Methionine (Met)‐enkephalin, leucine (Leu)‐enkephalin and their synthetic analogues were tested for effects on the spontaneous release of cortical acetylcholine (ACh) in vivo. The ability of naloxone to reverse the action of enkephalins on ACh release was compared with its action against morphine. An enkephalin analogue, structurally related to Met‐enkephalin, was tested for opiate antagonistic activity in ACh release experiments.

Intraventricular administration of Met‐enkephalin, Leu‐enkephalin, d‐Ala2‐Met5‐enkephalinamide (DALA) and d‐Ala2‐d‐Leu5‐enkephalin (DALEU) produced a dose‐related inhibition of cortical ACh release. Met‐ and Leu‐enkephalin were very similar both in their potency and the time course of their action on ACh release. Both DALA and DALEU were more potent and had a longer duration of action than Leu‐enkephalin. Systemic injections of two pentapeptides, d‐Met2‐Pro5‐enkephalinamide and d‐Ala2‐MePhe4‐Met5(O)‐ol‐enkephalin (33,824), produced a sustained inhibition of cortical ACh release.

Naloxone, administered systemically following the depression of ACh release induced by either intraventricular injections of enkephalins (DALA or DALEU), or systemic injections of enkephalins (d‐Met2‐Pro5‐enkephalinamide or 33,824), reversed this depression and restored the release to baseline levels. The effect of d‐Met2‐Pro5‐enkephalinamide on the release of ACh was reversed by naloxone with difficulty. Naloxone also reversed the inhibitory effect of systemic morphine and this reversal was associated with a large overshoot of ACh release. The latter was never observed in the enkephalin experiments.

Intraventricular injection of the pentapeptide, d‐Ala2‐d‐Ala3‐Met5‐enkephalinamide (TAAPM), at doses that did not influence the basal ACh release, blocked or reversed the inhibitory effect of morphine on this release. This peptide did not block the effect of the non‐opiate, chlorpromazine, under similar conditions. In two experiments TAAPM failed to reverse the inhibition of ACh release produced by systemically injected enkephalin, D‐Met2‐Pro5‐ enkephalinamide.

Effects of morphine and enkephalin on ACh release are discussed in terms of their action on different opiate receptors.
INVESTIGATION OF ACTION OF ENKEPHALIN ON THE SPONTANEOUS AND EVOKED RELEASE OF ACETYLCHOLINE FROM RAT CORTICAL AND STRIATAL SLICES
Authors: JHAMANDAS K. , ELLIOTT J.
Published: May 2015

The effects of two synthetic enkephalins, d‐Ala2‐Met5‐enkephalinamide (DALA) and d‐Ala2‐MePne4‐Met5‐(0)‐ol‐enkephalin (33,824) were tested on the spontaneous and stimulated release of acetylcholine (ACh) from rat cortical and striatal slices.

DALA, but not 33,824, caused a modest increase in spontaneous cortical ACh release. Neither enkephalin affected the release of cortical ACh induced by high potassium (25 mm) or veratridine (20 μm).

DALA had no effect on the release of ACh from striatal slices occurring spontaneously or in the presence of potassium (25 mm), veratridine (5 μm) or ouabain (10 μm). The enkephalin 33,824 also had no significant action on the striatal ACh release except that it caused a slight enhancement of veratridine‐evoked release.

It is suggested that enkephalins have no significant action on release of ACh from the cortex or striatum in vitro. Their action on ACh release from the cortex in vivo, seen in previous studies, may be exerted at a subcortical level.
THE EFFECTS OF DIPYRIDAMOLE ON THE GUINEA‐PIG ILEAL LONGITUDINAL MUSCLE‐MYENTERIC PLEXUS PREPARATION
Authors: DOWDLE E.B. , MASKE R.
Published: May 2015

The longitudinal muscle‐myenteric plexus strip prepared from guinea‐pig ileum has been used to study the actions of dipyridamole and its interactions with adenine derivatives.

Dipyridamole augmented the inhibitory effects of adenine derivatives on the twitch response induced by 0.1 Hz field stimulation of the preparation. This synergistic effect was apparent with relatively low concentrations of dipyridamole (10 to 100 nm) and after short pretreatment times (1 to 2 min) that did not inhibit the twitch response on their own. Appropriate studies suggested that dipyridamole‐adenosine synergism followed a pattern of facilitative agonist competition.

Dipyridamole did not inhibit either uptake of [3H]‐adenosine by the preparation or adenosine deaminase activity under the same conditions that it exhibited synergism with adenosine.

Higher concentrations of dipyridamole inhibited the twitch response, mainly by decreasing acetylcholine release but partly by a direct action on smooth muscle. The direct action of dipyridamole on muscle was not synergistic with adenosine.

Fluorescence microscopy showed preferential binding of dipyridamole to the myenteric plexus.
UPTAKE OF RADIOCALCIUM BY NERVE ENDINGS ISOLATED FROM RAT BRAIN: PHARMACOLOGICAL STUDIES
Authors: GRIPENBERG J. , HEINONEN E. , JANSSON S.‐E.
Published: May 2015

The uptake of radiocalcium by nerve‐ending particles isolated from the striatum of rat brain was studied using lanthanum as a quenching agent.

High potassium‐induced calcium uptake occurred in two phases: an initial rapid phase and a late slow phase. Following preincubation with CaCl2 2.2 mmol/l for 1 h, dopamine at 1 to 2 × 10−4 mol/l reduced the high potassium‐induced calcium uptake which occurred during the initial rapid phase by 66 and 25% at 2 and 4 s of incubation, respectively, but had no effect on the late slow uptake phase.

Haloperidol at 1 × 10−6 mol/l abolished the inhibitory effect of dopamine on the initial rapid phase of the high potassium‐induced calcium uptake. Haloperidol per se had no effect on the calcium uptake.

Dibutyryl cyclic adenosine monophosphate at 2.5 × 10−3 mol/l or prostaglandin E1 (PGE1) at 1 × 10−5 mol/l had no effect on the initial rapid phase of the high potassium‐induced calcium uptake by striatal synaptosomes. Neither of these agents affect calcium uptake by whole brain synaptosomes.

It appears that in the striatum, dopamine regulates the depolarization‐induced influx of calcium in presynaptic nerve endings. This mechanism could constitute a feed‐back inhibition for transmitter release in the striatum.