bluuebunny/crossref_metadata_2025 huggingface dataset:
Repetitive Pneumoperitoneum with Ozonized Oxygen as a Preventive in Lethal Polymicrobial Sepsis in Rats
Authors: Schulz S. , Rodriguez Z.Z. , Mutters R. , Menendez S. , Bette M.
Published: April 2003

The aim of this study was to test whether repetitive pretreatments of rats with ozonized oxygen at relatively low gas volumes into the abdomen (20 ml per rat per day) have any beneficial or detrimental effects on the course of a polymicrobial-induced lethal peritonitis. Peritonitis was induced in a surgical or a nonsurgical model by usage of fecal material from the cecum. As the biological read out we used the mortality analysis. To include possible mechanisms by which ozone might influence the septic outcome, we characterized the gene expression of the pro-inflammatory cytokines IL-1β, IL-2, and TNF-α mRNA in lymphoid organs. In both models, we found a significant beneficial influence of a dose-dependent O2/O3 pneumoperitoneum on the survival rate when compared to control animals or to room air. The ozone-enhanced survival seems to be independent from altered cytokine expression because there were no differences noticed in the levels of bacterial-induced gene expression of IL-1β and TNF-α in septic animals pretreated with ozonized oxygen when compared to control animals.
Influence of Omentectomy on Peritoneal Defense Mechanisms in an Experimental Model of Intra-Abdominal Infection
Authors: Agca B. , Paksoy M. , Polat E. , Aksin E. , Dirican A. , Durgun V. , Eren D.
Published: April 2003

Background/Aim: The omentum has an important role as part of peritoneal defense mechanisms. The aim of this study is to show the bactericidal activity of peritoneal fluid and the role of the omentum as a peritoneal defense mechanism in experimental animals with intra-abdominal infections. Methods: 40 male Spraque-Dawley rats weighing between 250 and 300 g were used in this study. The rats were randomly divided into four groups consisting of 10 animals. The operative procedures were done under sterile conditions. In group I sham laparotomy was done. In group II, the distal part of the cecum was ligated, and cecum perforation was performed. In group III, total omentectomy was performed after cecal ligation and perforation. In group IV only omentectomy was performed. Baseline and 2- and 4-hour peritoneal fluid samples were taken using a Pasteur pipette during laparotomy under anesthesia. Total peritoneal cells counts, bactericidal activity of peritoneal fluid, and types of phagocytic cells in the peritoneal fluid were assessed. Results: As compared with baseline values, the total peritoneal cell counts were increased at the 2nd and 4th h in all groups (p < 0.05). A significant increase was observed after 4 h as compared with 2 h in sham laparotomy, cecal ligation+perforation+omentectomy, and omentectomy groups (p < 0.05). A significant increase in the cell counts after 2 h was found in the other groups when compared to the sham laparotomy group (p = 0.0001). After 4 h, there was a significant difference between the groups, but especially prominent in the cecum ligation+perforation+omentectomy group (p = 0.0001). Proliferating colony counts of Escherichiacoli and Pseudomonas aeruginosa decreased after 2 h, and there was no proliferation in the subsequent cultures. It was observed that the macrophage counts significantly increased after 2 and 4 h as compared with baseline in intragroup assessments (p = 0.0001). In the intergroup assessment, an increase was observed in the macrophage counts at baseline and after 2 and 4 h, and this was significant in the cecal ligation+perforation+omentectomy group (p = 0.0001). In the omentectomy group, a significant decrease was observed in the macrophage counts between the 2nd and 4th h (p = 0.0001). Conclusion: Removal of the omentum in the presence of intra-abdominal infections causes the peripherally derived macrophages to take over the defensive role of macrophages of peritoneal origin as a compensatory mechanism, thus the peritoneal bactericidal activity against E. coli, the major pathogen in intra-abdominal infections, does not change after omentectomy.
Comparison of Free Amino Acids in Aqueous Humor of Farmed and Wild Salmon and of Six Species Additionally
Authors: Kjønniksen Inge , Bjerkås Ellen , Jellum Egil , Ringvold Amund
Published: April 2003

Objective: A comparative study was performed in order to identify aqueous humor amino acids possibly involved in cataract formation in farmed Atlantic salmon. Methods: Aqueous humor amino acids from farmed salmons with and without cataract were compared with levels in wild salmon and other animals of different evolutionary levels such as frog, crocodile, turkey, goose, minke whale, and cattle. Serum samples from wild and farmed salmon and minke whale were also analyzed. Results: The total amino acid concentration was lower in aqueous humor obtained from salmon, frog and crocodile compared to birds and mammals. Wild salmon had a higher content of amino acids than farmed salmon. Asparagine was absent in salmon aqueous humor and serum. Aqueous humor proline was readily detectable in wild salmon, birds, whale, and cattle, but not detectable in farmed salmon, frog and crocodile. The aqueous humor concentration of taurine was about seven- and fifty-fold lower compared to serum in wild and farmed salmon, respectively. The corresponding ratio in minke whale was 1:2. Conclusions: The results indicate a blood- aqueous barrier for taurine in farmed salmon. The lower total amino acid concentration and low aqueous humor proline concentration in farmed salmon should be further investigated.
Nonlinear Component of the Electroretinogram Recorded from the Posterior Pole of Normal and Highly Myopic Human Eyes
Authors: Yoshii Masaru , Yanashima Kenji , Nagasaka Eiichiro , Wada Hiroshi , Enoki Toshio , Okisaka Shigekuni
Published: April 2003

To extract the nonlinear component of the electroretinogram (ERG) from the posterior pole (pp) of the human ocular fundus and to evaluate the possibility of its clinical application, three types of stimulus modes – double-flash, single-flash, and delayed single-flash stimuli – were produced using a conventional electrophysiological system. A large hexagonal element was presented on a CRT monitor, and ppERGs were recorded from 14 normal eyes and 16 eyes of eight highly myopic patients. The nonlinear component of the ppERG was obtained by subtracting the single-flash ERG and delayed single-flash ERG responses from the double flash ERG response. Three peaks were commonly observed in the nonlinear component of ppERG, all of which were significantly depressed in patients with high myopia. ppERGs that can be obtained using a simple algorithm might be useful in clinical applications.
Quantification of Simulated Corneal Haze by Measuring Back-Scattered Light
Authors: Soya K. , Amano S. , Oshika T.
Published: April 2003

The Scheimpflug anterior eye segment analysis system EAS-1000 was modified to specifically quantitate the degree of corneal haze. In order to confirm the basic measurement performance of the new system, TSPC-3 hazemeter, in vitro experiments were conducted. Using white latex microsphere solutions, tests were performed for the linearity of the measurements, the influence of slit lamp illuminance and the influence of the length of the light path through the latex solution. The validity of Beer’s law was confirmed, indicating that a sufficiently wide range of latex concentrations (haze intensities) can be covered by the hazemeter. The scattering intensity measured with the hazemeter showed a significant linear correlation with the latex concentration. The obtained scattering intensity was directly proportional to the illuminance of the slit lamp. The ratio of integrated scattering values was proportional to that of the light path length. It was shown that the TSPC-3 hazemeter possesses sufficient capability for a quantitative evaluation of corneal haze.
Risk Factors for Atherosclerosis of Cervicocerebral Arteries: Intracranial versus Extracranial
Authors: Suwanwela Nijasri C. , Chutinetr Auruma
Published: April 2003

Objectives: To search for factors determining the site of atherosclerosis of the cervicocerebral arteries in patients from Bangkok (Thailand) with ischemic stroke in the carotid territory. Material and Methods: Patients with the clinical syndrome of stroke or transient ischemic attack in the carotid territory or with ocular stroke were retrospectively studied. They were divided into an intracranial and an extracranial carotid stenosis group based on their vascular imaging. The stroke risk factors were then compared. Results: There were 49 cases with extracranial carotid stenosis and 51 with intracranial stenosis. Among the patients with extracranial stenosis, 98% had associated intracranial disease, whereas none of those with intracranial stenosis had more than 50% of extracranial carotid stenosis. The presence of diabetes mellitus and a history of ischemic heart disease were found to be significantly more prevalent among patients with extracranial internal carotid artery stenosis. Conclusion: Diabetes mellitus as well as a history of ischemic heart disease were found to be more significantly prevalent in patients with combined extracranial internal carotid artery and intracranial stenosis. Extracranial carotid stenosis might represent a more severe atherosclerotic process of the cervicocerebral circulation when compared with intracranial stenosis.
Pharmakogenomik in der Frauenheilkunde
Authors: Huber J.C. , Schneeberger C. , Noe Marion , Tempfer C.
Published: April 2003

Leider besteht für diesen Artikel keine Zusammenfassung. Als Einstieg stellen wir den Textanfang zur Verfügung. Mehr als ein Jahrzehnt dauert bereits die wissenschaftliche Auseinandersetzung zwischen deutschen und österreichischen Endokrinologen bzw. Biochemikern, ob eine individuelle Hormonersatztherapie (HRT) sinnvoll ist und wie sie konkret aussehen soll. Dieses Thema wird nicht nur durch rezente Untersuchungen [1] aktualisiert, die klar belegen, dass die behandelten Frauen zu einem hohen Prozentsatz mit ihrer HRT unzufrieden sind und sie – vor allem wegen hyperöstrogenämischen Symptomen – nach relativ kurzer Zeit wieder beenden, sondern auch durch die HERS [2] und die Studie der Nurses’ Health Initiative [3], die sich von ihrem Design durch eine völlig unreflektierte Hormonverordnung auszeichnen. Die dabei vor allem gleich am Beginn auftretenden kardiovaskulären Probleme deuten bereits auf eine genetische Risikodisposition hin, in die stereotyp hineinsubstituiert wurde.
Effect of Nutritional Stress on the Hypothalamo-Pituitary-Gonadal Axis in the Growing Male Rat
Authors: Compagnucci Cecilia V. , Compagnucci Gabriela E. , Lomniczi Alejandro , Mohn Claudia , Vacas Irene , Cebral Elisa , Elverdin Juan C. , Friedman Silvia M. , Rettori Valeria , Boyer Patricia M.
Published: April 2003

Background/Objective: Nutritional dwarfing (ND) consists of a decrease in weight and height gain and delayed onset of puberty. The aim of the present investigation was to study the modifications induced in male rats by the nutritional stress of a mere 20% reduction in food intake which, however, started immediately after weaning. Materials and Methods: At weaning, male Wistar rats were divided into two groups: Control (C) and ND. C rats were fed ad libitum with a balanced rodent diet. ND received 80% of the diet consumed by C for 4 weeks (T4); then they were fed ad libitum for another 4 (T8) and 8 weeks (T12). The rats were studied at T0, T4, T8 and T12 for the effects of nutritional stress and refeeding on nutritional status, body composition, hypothalamic-pituitary-gonadal axis, and sperm morphology and concentration. Results: ND body weight and length diminished vs. C (p < 0.001). ND body fat percentage decreased 40% (p < 0.001) without change in the percentage of body protein content. The hypothalamic content of LHRH did not change. However, FSH, LH and testosterone serum levels had significantly decreased (p < 0.001) at T4 in ND rats. A 48.4 % decrease in serum leptin in the ND group was observed at T4 (p < 0.05). The absolute testicular and seminal vesicle weight was significantly decreased by ND at T4 (p < 0.001). At T4 the percentage of anomalies of caudal spermatozoa increased in about 64% (p < 0.001) of ND vs. C rats, despite the unchanged sperm concentrations. All parameters normalized during refeeding. Conclusion: In this model, a decrease in leptin due to nutritional stress could be responsible, at least in part, for the inhibition of reproductive function. Refeeding normalized all parameters studied.
The Distribution and Morphological Characteristics of Serotonergic Cells in the Brain of Monotremes
Authors: Manger Paul R. , Fahringer Heidi M. , Pettigrew John D. , Siegel Jerome M.
Published: April 2003

The distribution and cellular morphology of serotonergic neurons in the brain of two species of monotremes are described. Three clusters of serotonergic neurons were found: a hypothalamic cluster, a cluster in the rostral brainstem and a cluster in the caudal brainstem. Those in the hypothalamus consisted of two groups, the periventricular hypothalamic organ and the infundibular recess, that were intimately associated with the ependymal wall of the third ventricle. Within the rostral brainstem cluster, three distinct divisions were found: the dorsal raphe nucleus (with four subdivisions), the median raphe nucleus and the cells of the supralemniscal region. The dorsal raphe was within and adjacent to the periaqueductal gray matter, the median raphe was associated with the midline ventral to the dorsal raphe, and the cells of the supralemniscal region were in the tegmentum lateral to the median raphe and ventral to the dorsal raphe. The caudal cluster consisted of three divisions: the raphe obscurus nucleus, the raphe pallidus nucleus and the raphe magnus nucleus. The raphe obscurus nucleus was associated with the dorsal midline at the caudal-most part of the medulla oblongata. The raphe pallidus nucleus was found at the ventral midline of the medulla around the inferior olive. Raphe magnus was associated with the midline of the medulla and was found rostral to both the raphe obscurus and raphe pallidus. The results of our study are compared in an evolutionary context with those reported for other mammals and reptiles.
Effects of Insulin on Coronary Blood Flow in Anesthetized Pigs
Authors: Molinari C. , Battaglia A. , Grossini E. , Mary D.A.S.G. , Bona G. , Scott E. , Vacca G.
Published: April 2003

Insulin can influence the vasculature by a sympathetically mediated vasoconstriction and a vasodilatation; the latter effect predominates in the renal circulation of anesthetized pigs. We determined the effect of intravenous infusion of insulin on coronary blood flow in pentobarbitone-anesthetized pigs at constant heart rate, arterial pressure and blood levels of glucose and potassium. In 6 pigs, infusion of 0.004 IU kg–1 min–1 of insulin decreased coronary flow despite increasing left ventricular dP dtmax–1; when the latter was abolished by propranolol, the coronary flow response was augmented. The mechanisms of this response were examined in 22 pigs given propranolol. Phentolamine changed coronary flow response to an increase (6 pigs) and this was abolished by intracoronary injection of Nω-nitro-L-arginine methyl ester (L-NAME; 5 pigs). L-NAME augmented coronary flow response (6 pigs) and this was abolished by phentolamine (5 pigs). In 18 pigs given propranolol, three incremental doses of insulin caused graded coronary flow decreases whether L-NAME was given (6 pigs) or not (6 pigs) beforehand, and caused graded coronary flow increases after phentolamine (6 pigs). Thus insulin caused a coronary vasoconstriction mediated by sympathetic α-adrenergic effects and a vasodilatation related to the release of nitric oxide. The net effect was a coronary vasoconstriction.
Atherosclerotic Expansive Remodeled Plaques: A Wolf in Sheep’s Clothing
Authors: Pasterkamp Gerard , Fitzgerald Peter F. , de Kleijn Dominique P.V.
Published: April 2003

Geometric arterial remodeling is an important determinant of luminal narrowing in atherosclerotic disease. Expansive remodeling retards while constrictive remodeling accelerates luminal narrowing by plaque formation. Cross-sectional as well as follow-up studies revealed that expansive remodeling is associated with adverse cardiovascular events and a vulnerable plaque phenotype. Although the relation between expansive remodeling and plaque vulnerability is associative rather than causal, expansively remodeled plaques should be considered as a wolf in sheep’s clothes. Further understanding of the processes that regulate arterial remodeling and plaque rupture may lead to new strategies to responsibly manipulate these processes for the benefit of patient outcomes.
Association between the G Protein β3 Subunit 825t Allele and Radial Artery Hypertrophy
Authors: Hanon Olivier , Luong Vu , Mourad Jean Jacques , Bortolotto Luiz A. , Safar Michel , Girerd Xavier
Published: April 2003

The GNB3 C825T gene polymorphism has recently been identified and associated with hypertension, obesity and left ventricular hypertrophy. The aim of the study was to determine the relationship between the C825T polymorphism of the gene encoding for the G protein β3 subunit (GNB3 C825T) and vascular hypertrophy. We studied a cohort of 306 subjects (age 49 ± 12 years) without evidence of cardiovascular disease and never treated with cardiovascular drugs. Vascular phenotypes were evaluated for the common carotid and radial arteries using high-resolution echo-tracking devices. Genotype frequencies were in agreement with the Hardy-Weinberg equilibrium. For the radial artery, mean wall thickness was significantly higher in subjects carrying the 825T allele than in CC genotype subjects (240 ± 54 µm for CT genotype and 241 ± 53 µm for TT genotype vs. 222 ± 52 µm for CC genotype, p = 0.01). The frequency of the 825T allele was significantly different in subjects with (52%) and without (35%) radial artery hypertrophy (χ2 = 10.88, p < 0.001). The relative risk of radial artery hypertrophy in subjects carrying the 825T allele compared with those with the CC genotype was 3.02 (95% CI 1.53– 5.95). A logistic regression analysis indicated that the positive and significant association between the 825T allele and radial artery hypertrophy was independent of age, blood pressure, gender and BMI. In contrast, no association between genotypes and carotid artery wall thickening was observed. These results suggest that some genetic characteristics determine in part the patterns of radial artery geometrical changes. As the 825T allele is associated with vascular hypertrophy of a muscular artery but not with structural changes of an elastic artery, we hypothesize that the 825T allele may be a genetic marker of arteriolosclerosis.
Real-Time Detection of Activation Patterns in Individual Platelets during Thromboembolism in vivo: Differences between Thrombus Growth and Embolus Formation
Authors: van Gestel Miriam A. , Heemskerk Johan W.M. , Slaaf Dick W. , Heijnen Viviane V.Th. , Sage Stewart O. , Reneman Robert S. , oude Egbrink Mirjam G.A.
Published: April 2003

Knowledge on single platelet behavior and intracellular mechanisms during thromboembolism in vivo is scarce. In the present study, we used a new method that enables real-time detection and quantification of activation of individual platelets participating in a thromboembolic process in vivo, using their intracellular free Ca2+ concentration ([Ca2+]i) as a marker of activation. Isolated platelets were labeled with the Ca2+-sensitive fluorescent probe fluo-3 and injected into anesthetized rabbits so that 0.5–1% of their circulating platelets were labeled. Wall puncture of mesenteric arterioles resulted in thrombus formation followed by embolization. Fluorescence intensity changes of labeled platelets participating in this process were quantified. Within 30 min after injection, labeled platelets behaved similarly to native platelets, and fluorescence intensity was not influenced by dye leakage. Upon adherence to the stationary thrombus, platelets exhibited a prolonged [Ca2+]i increase, accompanied by shape change and degranulation, which is consistent with a role for strong platelet agonists like collagen. In contrast, when platelets adhered to a growing embolus their [Ca2+]i rise was transient, and they hardly showed shape change and degranulation, suggesting the involvement of weaker agonists like ADP. These results show, for the first time, the relation between single platelet activation patterns, which are different during thrombus growth and embolus formation, and their behavior in a thromboembolic process in vivo.
Thrombotic Thrombocytopenic Purpura Associated with Ticlopidine
Authors: Türken Orhan , Öztürk Ahmet , Orhan Bülent , Kandemir Gökhan , Yaylacı Mustafa
Published: April 2003

Thrombotic thrombocytopenic purpura is a syndrome characterized by hemolytic anemia, thrombocytopenia, neurological symptoms, fever and renal dysfunction. Although the syndrome is usually associated with various infections, vasculitis and pregnancy, rarely can it be associated with certain neoplasms and drugs such as ticlopidine. A 63-year-old woman, who had undergone coronary angioplasty and had been started on ticlopidine, was admitted to our clinic with a history of vomiting, fatigue, hematuria and deterioration in her cognitive abilities. Thrombotic thrombocytopenic purpura was diagnosed on the basis of neurological changes, an increase in LDH, urea, creatinine, indirect bilirubin levels, anemia and peripheral smear findings. Treatment was initiated with daily plasmapheresis and complete clinical and laboratory recovery developed. The patient was discharged after 14 days.
Interaction of Sickle Cell Trait with Hereditary Spherocytosis: Splenic Infarcts and Sequestration
Authors: Ustun Celalettin , Kutlar Ferdane , Holley Leslie , Seigler Maree , Burgess Russell , Kutlar Abdullah
Published: April 2003

The association of sickle cell trait (SCT) and hereditary spherocytosis (HS) has been reported in only 18 patients. Three of these 18 patients experienced splenic infarct or acute splenic sequestration. We report here a 46-year-old African-American male, the oldest reported case to date, who experienced episodes of hemolysis and severe left upper quadrant pain for the past 26 years. The patient had compensated hemolysis with splenomegaly. A CT scan of the abdomen revealed a large infarct in the spleen. The diagnosis of SCT was confirmed with isoelectric focusing, cation exchange and reverse-phase HPLC. The presence of a silent, interacting globin variant as the cause of hemolysis and sickling in the spleen was ruled out by sequencing of the α1-, α2- and β-globin genes. The diagnosis of HS was established by an osmotic fragility test. The interaction of HS and SCT leads to RBC dehydration with increased MCHC and intracellular Hb S concentration presumably favoring intrasplenic sickling and resultant splenic infarcts and sequestration as seen in this case.
Results of Hepatitis B Vaccination in Sarcoidosis
Authors: Mert Ali , Bilir Muammer , Ozaras Resat , Tabak Fehmi , Karayel Tuncer , Senturk Hakan
Published: April 2003

Background: Sarcoidosis is known to be associated with defects in cellular immunity, especially in reference to T  helper lymphocytes. Anergy to a tuberculin skin test is most characteristic of this disease. Objectives: To further the data on impaired immunity, we studied the antibody response to hepatitis B vaccination in patients with sarcoidosis. Methods: Serologic markers of hepatitis B virus (HBV) (HBsAg, anti-HBs, anti-HBc) were studied in 40 patients with sarcoidosis (32 female, 8 male; mean age: 45 ± 11 years, range: 25–66 years) with a mean duration of disease of 6 years. While all the markers were negative in 22 patients (55%), 2 had isolated anti-HBc positivity and 16 had both anti-HBc and anti-HBs antibodies. Thirty-five age- and sex-matched healthy subjects were studied as controls. Recombinant HBV vaccines (Genhevac B Pasteur, 20 µg) were administered (at 0 , 1, and 6 months) to 16 of the seronegative cases and the controls and antibody titres were measured 1 month after the last dose. The tuberculin skin test was negative in all cases. Results: While none of the vaccinees in the diseased group responded, the control group yielded an antibody response rate of 85.7% (30/35), with a mean titre of 257.9 mIU/ml. Conclusions: Patients with sarcoidosis were invariably unresponsive to standard vaccination, while some of the diseased subjects had already mounted a natural antibody response, either before or after the development of the original disease. Cellular immunodeficiency in sarcoidosis could be a suitable model for studying immunological interactions between HBV and the host.
Veria Operation
Authors: Kiratzidis Trifon , Iliades Theophilos , Arnold Wolfgang
Published: April 2003

The ‘Veria operation’ is a new technique for cochlear implantation. It is a non-mastoidectomy technique and uses the endaural approach for the cochleostomy and a direct tunnel drilled through the supero-posterior bony canal wall for the electrode. Two special instruments have been developed for this technique: a special perforator for the drilling of the direct tunnel and a safety electrode forceps for the insertion of the electrode. The method has been used in 101 cases with an age range from 2.5 to 75 years. 78 of them were primary operations and 23 revision cases. From the revisions, 18 were surgical failures and 5 were device failures. There were two complications: in 1 case there was a thick skin flap, which was corrected under local anesthesia, and in 1 malformation case there was a retrograde insertion to the vestibule and the posterior semicircular canal, corrected 6 weeks later. The analysis of the results shows that this method has certain advantages, which are: it is simple and therefore the learning curve is fast; it is safe for the facial nerve, as the drilling is precisely controlled by the special perforator; it produces minimal bone trauma and due to fast healing, it permits early fitting a few days after operation; it is suitable for the difficult and revision cases and it can be used for very small children where the mastoid may have not been yet sufficiently developed.
Gender Comparisons of Control of Breathing and Metabolism in Conscious Mice Exposed to Cold
Authors: Schlenker Evelyn H. , Hansen Susan N. , Pfaff Donald W.
Published: April 2003

We evaluated the effects of 2 h of warm (24°C) and cold (6°C) exposure on metabolism and ventilation (v̇E) in conscious male and female Harlan ICR Swiss Webster mice exposed to air, and 8% O2 in N2 (hypoxia) and to 5% CO2 in O2 (hypercapnia) for 2 min each at both temperatures. All cold-exposed mice increased O2 consumption (v̇O2), and maintained body temperature. Cold-exposed females doubled their tidal volume, increased their v̇E fivefold, and doubled their ventilatory equivalent to v̇O2 (v̇E/v̇O2). In contrast, cold-exposed males decreased tidal volume and doubled v̇E relative to warm exposure. The ventilatory equivalent of males was similar during warm and cold exposure. During warm exposure, mice of both genders increased their ventilatory responses to both hypoxia and to hypercapnia by different mechanisms. In contrast, during cold exposure, these responses were blunted relative to air measurements in females and decreased below air values in males. Thus, cold exposure was able to elicit gender-specific ventilatory and metabolic responses.
Ovariectomy-Induced Increases in Hypothalamic Serotonin-1A Receptor Function in Rats Are Prevented by Estradiol
Authors: Raap Dani K. , DonCarlos Lydia L. , Garcia Francisca , Zhang Yahong , Muma Nancy A. , Battaglia George , van de Kar Louis D.
Published: April 2003

The present study investigated the effects of long-term estradiol withdrawal (ovariectomy) on hypothalamic serotonin-1A (5-HT1A) receptor signaling. Changes in neuroendocrine responses to the 5-HT1A agonist 8-OH-DPAT and levels of Gz protein in the hypothalamus were used to examine 5-HT1A receptor signaling. Five days following ovariectomy, rats received daily injections of either 2 µg of β-estradiol 3-benzoate or vehicle (subcutaneously) for 2, 4 or 14 days. Twenty-four hours after the last injection, and 15 min prior to sacrifice, rats were injected with (±)8-OH-DPAT (50 µg/kg, s.c.) or saline. Estradiol treatment did not alter basal corticotropin (ACTH) or oxytocin levels. Injection of (±)8-OH-DPAT produced significant increases in plasma ACTH and oxytocin levels. In the vehicle-treated rats, hormone responses to 8-OH-DPAT were enhanced in rats that received injections for 14 days compared with rats that received injections for either 2 or 4 days. Estradiol treatment for 4 or 14 days blunted this enhanced ACTH response to 8-OH-DPAT, whereas the oxytocin response to 8-OH-DPAT was only blunted after 14 daily injections of β-estradiol 3-benzoate. The treatment with β-estradiol 3-benzoate (2 µg/rat) did not reduce membrane-associated Gz protein levels in the paraventricular nucleus of the hypothalamus. Hence, the inhibitory influence of a low dose of β-estradiol 3-benzoate on 5-HT1A receptor signaling in the hypothalamus is not accompanied by a change in the levels of Gz protein in the paraventricular hypothalamic nucleus. Results from the present study indicate a supersensitivity of 5-HT1A receptors after withdrawal of estradiol and suggest that estradiol suppresses 5-HT1A receptor signaling.
Ghrelin Is No Longer Able to Stimulate Growth Hormone Secretion in Patients with Cushing’s Syndrome but Instead Induces Exaggerated Corticotropin and Cortisol Responses
Authors: Leal-Cerro Alfonso , Torres Elena , Soto Alfonso , Dios Elena , Deghenghi Romano , Arvat Emanuela , Ghigo Ezio , Dieguez Carlos , Casanueva Felipe F.
Published: April 2003

Growth and growth hormone (GH) secretion are blunted or severely impeded in chronic hypercortisolism and in patients with Cushing’s syndrome. A mechanistic explanation for the effect however has yet to be provided. On the other hand, several properties of ghrelin, a new peptide recently identified as the endogenous ligand of the GH secretagogue receptor, are still largely unknown. The two aims of this study were to observe whether ghrelin-mediated GH secretion was altered, and to characterize the corticotropin (ACTH) and cortisol response to this new stimulus in patients with Cushing’s disease. Ten patients with active Cushing’s disease (6 harboring microadenomas and 4 with macroadenomas) and 10 sex- and age-matched controls were studied. Ghrelin was administered at a dose of 1 µg/kg i.v. and GH, ACTH and cortisol analyzed in duplicate. In control women, ghrelin induced GH secretion to levels of 74.4 ± 12.8 µg/l, while chronic hypercortisolism severely reduced the ghrelin-mediated GH release in all patients with Cushing’s disease (peak values 17.7 ± 5.2 µg/l). The slightly, but significantly higher adiposity of patients vs. controls may have contributed to the effect, since a significant negative correlation (r = 0.639) was found between the amplitude of the GH peak and body mass index. In control women, ghrelin increased ACTH and cortisol levels, with peaks at 57.4 ± 19.0 ng/l and 162 ± 16 µg/l, respectively. This secretion was enhanced in Cushing’s syndrome patients, with ACTH and cortisol values of 380.7 ± 109.8 ng/l and 338 ± 81 µg/l respectively, both significantly higher than in controls. In conclusion, ghrelin-induced GH secretion was severely blunted in patients with active Cushing’s syndrome, in addition to a remarkable hyper-response in ACTH and cortisol secretion. These findings could have implications for the understanding of the physiology and physiopathology of interactions between GH and ACTH regulation.
Immunologic Changes during Minimally Invasive Surgery
Authors: Jacobi C.A. , Wenger F. , Opitz I. , Müller J.M.
Published: April 2003

Although recent experimental and clinical trials have documented that postoperative inflammation and changes in different immunologic parameters are less pronounced after laparoscopic approaches in comparison to open surgery, it still remains unclear what influence the pneumoperitoneum itself has on immunologic defense and function. This is mainly due to the endpoints of the different studies which investigate changes in the so-called immunologic parameters (cell subunits, C-reactive protein, cytokines, catecholamines or other stress hormones in plasma samples) rather than analyzing immunologic functions, such as cell activation, production of proteins, cell proliferation or in vivo immune defenses. So far, especially in clinical trials, no correlation has been demonstrated between the changes in immunologic parameters and relevant postoperative clinical endpoints, such as postoperative complications. Thus further clinical prospective randomized studies with relevant clinical endpoints and additional investigations of immunologic parameters are needed to prove the consequences of either minimally invasive surgery or open procedures on postoperative immune functions.
The Apoptosis Interruptus Hypothesis for the Generation of Chromosomal Rearrangements in Cancer and Evolution
Authors: Thaler David S. , Nackerdien Zeena
Published: April 2003

Chromosomal rearrangements are key events in cancer and evolution. These chromosomal rearrangements are dependent upon either legitimate, i.e. homologous, or illegitimate recombination of DNA. Recombination – legitimate or illegitimate – is often limited by the number of double-strand breaks (DSBs) in DNA. The number of DSBs in several biological systems is in turn limited by the activity of endogenous endonucleases. All mammalian cells harbor multiple endonucleases, including an important class that are normally kept quiescent but become activated during apoptosis (programmed cell death), either by removal of an inhibitory subunit or by migration out of mitochondria. Commitment to apoptosis need not be absolute; under certain conditions cells can ‘withdrawafter initiating the apoptosis program. We hypothesize that endogenous endonucleases, activated via ‘apoptosis interruptus (AI) in somatic tissue, initiate a portion of chromosomal rearrangements found in cancer. Chromosome rearrangements are also integral to speciation; AI in the germ line could generate gametes with chromosomal rearrangements. AI can be considered as the resolution of a dialectical conflict between individual survival of a cell and survival of the multicellular organism of which the cell is part.
Comorbid Psychiatric Disorders Predict and Influence Treatment Outcome in Female Alcoholics
Authors: Haver Brit
Published: April 2003

Drinking patterns, psychiatric comorbidity and personality disorders (PD) at intake and at a 2-year follow-up were studied in 120 female alcoholics early in their treatment career. At follow-up, the women had improved their drinking patterns, but their mental health still differed significantly from women of the general population. Psychiatric comorbidity at intake correlated with a significantly worse drinking and mental health outcome. Subjects with high scores on phobias more frequently dropped out of treatment and thereby had a worse drinking outcome. Subjects with depression at follow-up also had a poorer drinking outcome, as well as subjects with schizoid PD. When tested by multivariate analyses, only depression at follow-up contributed significantly to the increased explained variance in drinking outcome when controlling for drinking pattern and treatment duration.
Topical Treatment in Acne: Current Status and Future Aspects
Authors: Gollnick Harald P.M. , Krautheim Andrea
Published: April 2003

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2–5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO2 laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.
Aberrant Receptor-Mediated Cushing’s Syndrome
Authors: Bertagna Xavier , Groussin Lionel , Luton Jean-Pierre , Bertherat Jérôme
Published: April 2003

Multiple alterations of G-protein-coupled receptors and G-proteins regulating intracellular transduction signal have been described in endocrine tumours. In Cushing’s syndrome, aberrant or ‘illicit’ expression of membrane receptors (mainly G-protein-coupled receptors) has been observed in adrenal adenomas and adrenocorticotropic hormone (ACTH)-independent macronodular bilateral adrenal hyperplasia. The best characterized example to date is the aberrant expression of the gastric inhibitory polypeptide receptor that causes ‘food-dependent hypercortisolism’. Aberrant expression of the luteinizing hormone, β2-adrenergic, interleukin receptors have also been reported. The level of expression of the vasopressin V1a receptor correlates with the direct (ACTH-independent) cortisol response to vasopressin.
Methods and Reproducibility of Measurement of Resistivity in the Calf Using Regional Bioimpedance Analysis
Authors: Zhu Fansan , Sarkar Shubho , Kaitwatcharachai Charoen , Greenwood Roger , Ronco Claudio , Levin Nathan W.
Published: April 2003

The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. Methods: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. Results: The mean resting resistivity (ρ₀) in normal subjects was 532.6 ± 95 Ω·cm rising to 583.9 ± 99.7 Ω·cm when cuff pressure was applied (ρp). The average values of ρ₀ and ρp in patients post-dialysis were 489 ± 74 and 537 ± 77 respectively showing that there were no significant differences in ρ₀ and ρp between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were –3.66 ± 4.45 and –1.44 ± 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 ± 2.29% while post-dialysis body weight varied by 0.17 ± 0.47%. Conclusion: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.
Renal Cell Therapy Is Associated with Dynamic and Individualized Responses in Patients with Acute Renal Failure
Authors: Humes H. David , Weitzel William F. , Bartlett Robert H. , Swaniker Fresca C. , Paganini Emil P.
Published: April 2003

Background: Renal cell therapy in conjunction with continuous hemofiltration techniques may provide important cellular metabolic activities to patients with acute renal failure (ARF) and may thereby change the natural history of this disorder. The development of a tissue-engineered bioartificial kidney consisting of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 109 human renal proximal tubule cells provides an opportunity to evaluate this form of therapy in patients with ARF in the intensive care unit. Methods: Nine patients with ARF and multi-organ systems failure (MOSF) have been treated so far with a tissue-engineered kidney in an FDA-approved Phase I/II clinical study currently underway. Acute physiologic parameters and serum cytokine levels were assessed before, during and after treatment with a bioartificial kidney. Results: Use of the RAD in this clinical setting demonstrates maintenance of cell viability and functionality. Cardiovascular stability appears to be maintained during RAD treatment. Human tubule cells in the RAD demonstrated differentiated metabolic and endocrinologic activity. Acute physiologic and plasma cytokine data demonstrate that renal cell therapy is associated with rapid and variable responses in patients with ARF and MOSF. Conclusion: The initial clinical experience with the bioartificial kidney and the RAD suggests that renal tubule cell therapy may provide a dynamic and individualized treatment program as assessed by acute physiologic and biochemical indices.
Comparison of Human Papillomavirus Type 16 L1 Chimeric Virus-Like Particles versus L1/L2 Chimeric Virus-Like Particles in Tumor Prevention
Authors: Wakabayashi Mark T. , Da Silva Diane M. , Potkul Ronald K. , Kast W. Martin
Published: April 2003

Chimeric human papillomavirus (HPV) virus-like particles (cVLPs) with the HPV16 E7 antigen fused to either the major capsid protein, L1, or the minor capsid protein, L2, have been used independently to protect against the formation of HPV-induced tumors in animal models. However, the advantages and disadvantages of both types of particles with respect to production and vaccine efficacy have never been analyzed. Therefore, in this study, we compared cVLPs with the HPV16 E7 antigen fused to L1 versus cVLPs with E7 fused to L2 with respect to their ability to protect mice from tumor challenge. The first 57 amino acids of E7 were used to overcome the size limitation and limited VLP production imposed by inserting polypeptides into L1 cVLPs. C57BL/6 mice were immunized with the above cVLPs at various doses. Tumor challenge was then performed with HPV16 E7-positive TC-1 cells. HPV16 L1-E7(1–57) was superior to HPV16 L1/L2-E7(1–57) in eliciting tumor protection at equivalent doses, although both types of particles were able to protect mice. Both cVLPs induced a specific cytotoxic T lymphocyte (CTL) response to the H2-Db-restricted E7 peptide (E749–57) as determined by an ELISPOT assay and tetramer staining; however, immunization with the L1-E7(1–57) cVLPs resulted in twofold higher CTL precursor frequencies. Our results demonstrate that cVLPs with the antigen fused to L1 are a more efficient vaccine with respect to tumor prevention than cVLPs with the antigen fused to L2. At the same time, however, L1 cVLPs are limited by the size of the antigen that can be incorporated and in the amount of cVLP that can be obtained from cultures when compared to L1/L2 cVLPs. This balances out their superior ability to induce protective immunity.
RNA Bacteriophage Capsid-Mediated Drug Delivery and Epitope Presentation
Authors: Brown William L. , Mastico Robert A. , Wu Min , Heal Karen G. , Adams Chris J. , Murray James B. , Simpson Jeremy C. , Lord J. Michael , Taylor-Robinson Andrew W. , Stockley Peter G.
Published: April 2003

Objective: To use our knowledge of the three-dimensional structure and self-assembly mechanism of RNA bacteriophage capsids to develop novel virus-like particles (VLPs) for drug delivery and epitope presentation. Methods: Site-directed mutagenesis of a recombinant MS2 coat protein expression construct has been used to generate translational fusions encompassing short epitope sequences. These chimeric proteins still self-assemble in vivo into T = 3 shells with the foreign epitope in an accessible location. Covalent conjugation has also been used to generate RNA stem-loops attached to the toxin, ricin A chain, or to nucleotide-based drugs, that are still capable of stimulating self-assembly of the capsid in vitro. These packaged drugs can then be directed to specific cells in culture by further covalent decoration of the capsids with targeting molecules. Results: Chimeric VLPs are strongly immunogenic when carrying either B or T cell epitopes, the latter generating cytokine profiles consistent with memory responses. Immune responses to the underlying phage epitopes appear to be proportional to the area of the phage surface accessible. Phage shells effectively protect nucleic acid-based drugs and, for the toxin construct, make cell-specific delivery systems with LD50 values in culture sub-nanomolar. Conclusion: VLP technology has potential for therapeutic and prophylactic intervention in disease.
Relationship between Adrenomedullin and Vasopressin-Aquaporin System under General Anesthesia
Authors: Ogura Toshio , Morita Kiyoshi , Takeuchi Mamoru , Otsuka Fumio , Iwasaki Tatsuo , Oe Katsunori , Matsuura Kazuharu , Tobe Kazuo , Mimura Yukari , Kishida Masayuki , Makino Hirofumi , Hirakawa Masahisa
Published: April 2003

Aim: The roles of adrenomedullin (AM) in body fluid balance under general anesthesia were investigated. Methods: Time course changes in plasma osmolality, AM, arginine vasopressin (AVP), and urinary aquaporin 2 (AQP2) in 17 patients undergoing abdominal surgery under general anesthesia were examined. Results: Increases in plasma AM levels were observed in parallel with increases in the levels of urinary AQP2/creatinine (Cr) before induction and 90 and 180 min after initiation of anesthesia. Significant correlations between plasma AM and urinary AQP2/Cr (r = 0.62, p < 0.0001) as well as urinary AVP/Cr and AQP2/Cr (r = 0.60, p < 0.0001) were uncovered. Multivariate stepwise analysis identified plasma AM as the critical independent factor affecting urinary AQP2/Cr level. Conclusion: A novel correlation of AM and AQP2 which overlays an AVP-AQP2 system may play a key role in fluid homeostasis during general anesthesia.