Showing papers by "Tehran University of Medical Sciences published in 2000"

Comparison of the immune profile of nonhealing cutaneous Leishmaniasis patients with those with active lesions and those who have recovered from infection.

Abstract: Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.

Dipyridamole in the treatment of schizophrenia: adenosine-dopamine receptor interactions.

Abstract: Objective: There is growing interest in investigating the adenosine–dopamine interaction in the ventral striatum. Adenosine plays a role opposite to dopamine in the striatum and adenosine antagonists, like caffeine, produce similar effects to increased dopaminergic neurotransmission in the striatum. In particular, a strong antagonistic interaction between adenosine A2A and dopamine D2 receptors takes place in the striopallidal GABAergic neurones. Therefore, adenosine agonists or uptake inhibitors provide a potential new treatment for schizophrenia. We undertook a pilot trial to investigate whether the combination of haloperidol with dipyridamole, an uptake inhibitor of adenosine, was more effective than haloperidol alone. Methods: Thirty patients who met the DSM IV criteria for schizophrenia completed the study. Patients were allocated in a random fashion, 16 to haloperidol 20 mg/day plus dipyridamole 75 mg/day and 14 to haloperidol 20 mg/day plus placebo. Results: Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and dipyridamole was significantly better than haloperidol alone in decreasing positive and general psychopathology symptoms as well as PANSS total scores. Conclusion: Dipyridamole may be of therapeutic benefit in treating schizophrenia in combination with neuroleptics. However, a larger study to confirm our results is warranted.

Meningiomas of the central nervous system occurring below the age of 17: report of 24 cases not associated with neurofibromatosis and review of literature.

Abstract: The objective of this work was to gain more insight into the controversial characteristics of meningiomas occurring during childhood and adolescence. Management of meningiomas is an important field in pediatric neurosurgery. Every pediatric neurosurgeon has tried to resolve the problems relating to the clinical characteristics, biological behavior and outcome of this interesting and almost benign pathology, which rarely occurs in the first two decades of life. The records on central nervous system (CNS) tumors held by the two major neurosurgery centers of Tehran Medical University and Arad General Hospital were prospectively collected during last 15 years. Complete medical records are available for all 24 cases, and long-term follow-up was achieved 19 patients. All the cases were diagnosed and treated after the introduction of computed tomographic (CT) scanning. Angiography and magnetic resonance imaging (MRI) were performed as complementary studies in some cases. The sample consisted of 13 girls and 11 boys. The age range at the time of diagnosis varied between 2 and 17 years, with a mean of 9.47 and standard deviation of 3.43. Fifteen patients were below 10 years of age (62.5%), and 9 of them were between 10 and 17 years old (37.5%). The most common presenting symptoms, in declining order of frequency, were headache, epilepsy and focal neurological deficits. Similar cases associated with neurofibromatosis either at the time of presentation with meningioma or during the follow-up period were excluded (5 cases). The size of the presenting tumor was more than 5 cm in diameter in 17 cases. The locations of the lesions, taken as the site of the presumed widest dural base in each case were: spinal, orbital, ethmoidal and sphenoethmoidal in 1 case each, petroclival in 2, and tentorial or supratentorial in 18 patients. The only predisposing factor in this series of childhood meningiomas was whole-axis irradiation for previous malignancy in the case presenting with cervical intradural meningioma. There have been no surgical deaths, and gross total excision of the lesions was achieved in 21 cases. Tumor recurrence was observed during the follow-up period in 6 cases (25%). The follow-up period varied between 2 and 165 months, with a median interval of 130.2 months. This series of pediatric CNS meningiomas comprises almost 1.08% of all meningiomas operated on by the authors during the last 15 years and it also accounts for about 1.1% of all pediatric CNS tumors encountered. This series of patients has certain characteristics regarding sex distribution, unusual size, peculiar localizations, special histological features and benign clinical behavior distinguishing it from other series reported in the literature.

Synthesis and in vitro antifungal and cytotoxicity evaluation of thiazolo-4H-1,2,4-triazoles and 1,2,3-thiadiazolo-4H-1,2,4-triazoles.

Abstract: The increasing clinical importance of drug-resistant fungal pathogens has lent additional urgency to microbiological and antifungal research. Various thiazolo(or 1,2,3-thiadiazolo)thiosemicarbazides (2a-2e), 3-thiono-1,4-dihydrotriazolothiazoles-(or 1,2,3-thiadiazoles) (3a-3e), their related substituted thio-4H-1,2,4-triazoles (4a-4p) and sulfones (5a-5o) were synthesized. Most of the compounds tested for antifungal activity exhibited significant effects against Cryptococcus neoofrmans and Sacchromyces cerevisiae at MIC ranges of 0.53 to 12.5 micrograms/mL, whereas their activities were moderate against Candida albicans and weak against Aspergillus fumigatus. At 10 ppm concentration, all compounds showed low toxicity on brine shrimps (higher than 80% survival), except compounds 4c and 2c. At 100 ppm concentration most of the compounds showed toxicity except compounds 2b, 2e, 3c, 3d, 3e, and 4e. Compounds 4b, 4c, and 4h showed in vitro cytotoxicity against Kbalb cell lines and compounds 4c and 4g against 143B cell lines at 0.1 mM concentration.

Characteristics and outcome of injured patients treated in urban trauma centers in Iran.

Abstract: Background: Because of the need to improve the quality of care of trauma patients in our country, we decided to evaluate the epidemiology and find the most powerful tool for prediction of survival. The Trauma and Injury Severity Score (TRISS) has been known as conventional method for this purpose. We planned to test its ability for prediction of survival of our trauma patients, and also we wanted to compare its ability with the New Injury Severity Score (NISS) in combination with Revised Trauma Score (RTS) and age. We used the most suitable model to evaluate the trauma care in our centers. Methods: From the Tehran University data registry on trauma patients of three different hospitals during 1 year, we selected trauma patients admitted to hospital for at least 1 day and all those patients who were declared dead at the emergency department. Epidemiologic description of patients has been given and evaluation of TRISS and (NISS + RTS + age) for prediction of survival has been performed. We determined factors affecting mortality and morbidity, evaluated hospitals, and analyzed patients admitted directly and the patients transferred from other hospitals. Results: A total of 2,662 patients had complete data necessary for the calculation of probability of survival based on the TRISS method. The population at risk for trauma was the young, especially students and industrial workers. The major mechanisms of trauma were road traffic crashes and falls. The time expenditure and means of transportation as well as the time of stay in emergency department all seemed to be far less than optimal. We found that TRISS has higher performance than (NISS + RTS + age). Conclusion: Based on our descriptive findings, we proposed some suggestions that seem to be necessary for improvement of trauma care in our centers. Among them were improved measures for prehospital service, and emergency department and other health care units of our centers. The findings of this study suggest that conducting trauma surgery training programs and direct transportation to trauma centers can improve the outcome of trauma patients. We conclude that small sample size, mixing penetrating trauma cases with blunt trauma cases, and differences in the mechanism of trauma between study populations may be responsible for the difference between our results and others.

Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal.

Abstract: Background: A variety of detoxification methods have been utilized for the treatment of opiate withdrawal syndrome, of which alpha-adrenergic agonists have attracted considerable attention over the last two decades. However, accumulating evidence in rats shows the efficacy of the GABAB receptor agonist, baclofen, in reducing alcohol intake and self-administration of cocaine. Objective: To examine the ability of baclofen, in the management of opiate withdrawal. Method: A total of 62 opiate addicts randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0·8 mg for clonidine given three times a day in divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). Results: Baclofen and clonidine were equally effective in treating the physical symptoms of withdrawal syndromes. However, baclofen showed a significant superiority over clonidine in the management of mental symptoms. Conclusion: These results suggest that baclofen might be a novel therapeutic agent for opiate withdrawal syndrome. However, a larger study to confirm our results is warranted.

Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease

Abstract: OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking. AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients. METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test. RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04). CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.

Evaluation of hypotonic preswelling method for encapsulation of enalaprilat in intact human erythrocytes.

Abstract: The hypotonic preswelling method for encapsulation of drugs in intact human erythrocytes was evaluated using enalaprilat as a model peptide-like drug. Several process variables, including volume, concentration, pH, and method of addition of drug solution, type of erythrocyte-suspending medium, temperature, initial packed density of erythrocytes, and individual process steps, were exploited with respect to their effects on the loading parameters (i.e., loaded amount, efficiency of entrapment, and cell recovery). In addition, the probable mechanism by which the erythrocytes were loaded by enalaprilat at the point of lysis was shown to be a simple concentration gradient-based diffusion through membrane openings occurring on hemolysis. Finally, the adopted method was validated, and the results showed a considerable degree of reproducibility and recovery for the entire loading procedure.

High rate of tetracycline resistance in Streptococcus pyogenes in Iran: an epidemiological study.

Abstract: Streptococcus pyogenes, a major human pathogen, is still considered susceptible to beta-lactams, but for other relevant antibiotics, highly variable resistance rates have been reported. Since no data were available from Iran, we tested 1,335 throat isolates from two different regions of the country for their antibiotic susceptibilities and, for comparison, a collection of 80 strains isolated from 1989 to 1991. Erythromycin resistance was uncommon (0.6%), whereas an overall high rate of tetracycline resistance was found, increasing between 1989-1991 and 1995-1997 from 23 to 42%. The tetracycline-resistant strains belonged to more than 10 different T types, the majority being types 4, 11, and B3264. By conventional M typing of 406 tetracycline-resistant isolates, more than 20 different M types were found. Approximately 50% of the strains were nontypeable by T agglutination as well as serological M typing; however, by genotyping by a combined PCR-capture-enzyme-linked immunosorbent assay, many of these strains were successfully emm typed. We conclude that the high rate of tetracycline resistance among Iranian S. pyogenes isolates is due to multiclonal dissemination of resistance within the streptococcal population rather than epidemic spread of single clones.

Field trial for the control of zoonotic cutaneous leishmaniosis in Badrood, Iran.

Abstract: Background: Due to the resurgence of zoonotic cutaneous leishmaniosis (ZCL) in some nonendemic areas of Iran, extensive studies have been conducted on the epidemiology of the disease in different parts of the country in recent years. The objective of this study was to determine the effects of rodent control on the reduction of the incidence of ZCL in an endemic area in Badrood, Iran. Patients and Methods: A survey was carried out in a circle around two villages between April 1997 and January 1999. The control strategy adopted in 1997 consisted of the destruction of the colonies of gerbilline rodents by digging in a radius of 500 m from houses in the intervention area. Opened burrows were baited with zinc phosphide. One village was used as control. Evaluation was made in 1998 and no other control measures were carried out in the area. Case findings were done by house-to-house visits once every season during 1997 and 1998, and all the inhabitants of the selected villages were examined. Results: The average reduction of rodent holes was calculated at 87.4% one year after the first baiting in the intervention area. Changes in the number of rodent holes and the incidence of the disease in the intervention and control villages were statistically significant ( P-value <0.000001). Conclusion: Our evaluation demonstrated that the control program reduced the incidence of ZCL 12-fold in the treated village compared to the control at the end of the first year of operation, and to more than one-fifth of its original level after two years. The results show that the field control method is very effective in destroying rodents and reducing the incidence of ZCL on a small scale and in special circumstances. Ann Saudi Med 2000;20(5-6):386-389. Zoonotic cutaneous leishmaniosis (ZCL) is a major health problem in many rural areas of Iran. Recently, a new focus of ZCL was found in villages around the town of Badrood (Natanz county) at the foothills of the Karkas mountains in central Iran. The incidence of the disease among 726 inhabitants in two villages was calculated at 142.4 per thousand in 1996. The majority (42.9%) had one lesion, 22.2% had two lesions, and 34.9% had three or more lesions. The most commonly involved part of the body was the hands (37.6%), followed by the legs (31.1%), face (29.4%), and other parts of the body (1.9%). Three small mammals—Meriones libycus (58%), Rhombomys opimus (40%) and Hemiechinus auritis (2%)—were present around the selected villages. M. libycus and R. opimus are the main reservoir hosts in this new focus of ZCL in Iran. 1

Volatile constituents of Nepeta denudata Benth. and N. cephalotes Boiss. from Iran.

Abstract: The composition of the essential oils of Nepeta denudate Benth. and N. cephalotes Boiss., which are endemic to Iran, was investigated by means of GC, GC/MS and 1H-NMR spectra of the main compounds, 1,8-cineole (48.0%), myrtenol (5.0%), β-pinene (4.6%) and trans-pinocarveol (4.5%) were the main components among the 21 constituents characterized in the oil of N. denudata, representing 85.7% of the total components detected. Ten compounds were identified in the oil of N. cephalotes representing 78.5% of the total oil with 4aα, 7α, 7aα-nepetalactone (35.1%), β-pinene (18.2%) and 1,8-cineole (11.4%) as the major constituents. The structure of 1,8-cineole, nepetalactone and β-pinene were confirmed by their 1H-NMR spectra.

In Vitro Release Studies of Piroxicam from Oil-in-Water Creams and Hydroalcoholic Gel Topical Formulations

Abstract: The importance of piroxicam, a therapeutic anti-inflammatory drug, is well known. Because of gastrointestinal disorders, dermatological dosage forms are recommended most. In our first studies, oil-in-water (O/W) creams of piroxicam (1% concentration) were prepared using glyceryl monostearate (GMS), stearic acid, and triethanolamine as additive ingredients. In our second studies, hydroalcoholic transparent gel formulations of this drug in a 0.5% concentration were prepared using hydroxypropylcellulose (HPC) as the gelling agent. The release of piroxicam from all formulations via dialysis through a cellulose membrane into phosphate buffer pH 6.8 at 37 degrees C was studied. The effects of additives such as propylene glycol and 2-propanol on the drug release were also investigated. The release profiles from the standpoint of diffusion-controlled processes, as well as zero-order and first-order kinetics, were evaluated, and relevant parameters, such as diffusion coefficient, permeability coefficient, and partition coefficient, were calculated. The release obeys both the diffusion mechanism and first-order kinetics. The drug release from gel formulations containing 10%, 20%, and 30% propylene glycol was decreased due to the enhancement of viscosity. However, the limpidity of these formulations was improved. Moreover, the release of drug from gel formulations containing 15% and 20% of 2-propanol was increased. These results show that a hydroalcoholic gel formulation with HPC is a more suitable preparation of piroxicam when compared with an O/W cream formulation.

L-arginine/nitric oxide pathway and interaction with lead acetate on rat submandibular gland function.

Abstract: : The effects of lead acetate, L-arginine (nitric oxide precursor) and L-NAME (nitric oxide synthesis inhibitor) on rat submandibular secretory function were studied. Pure submandibular saliva was collected intraorally from anaesthetized rats by a micro polyethylene cannula using pilocarpine as secretagogue. Treatment for twenty-eight days with three doses of lead acetate (0.01%, 0.04%, 0.05% w/v) in drinking water caused significant alterations on salivary function. Salivary flow rate was decreased by lead at all doses used. The total protein concentration and amylase activity of saliva were both decreased by lead (0.04% and 0.05%). All doses of lead decreased saliva calcium concentrations. Two weeks' treatment of rats by L-arginine (2.25% w/v) and L-NAME (0.7% w/v) in drinking water also affected the saliva secretory function. L-Arginine caused increase in submandibular gland weight. The saliva flow rate was reduced by L-NAME. The total protein concentration of saliva was increased by L-arginine and decreased by L-NAME. Amylase activity was reduced by L-arginine treatment. Calcium concentration was reduced by L-arginine and increased by L-NAME. Concurrent L-arginine treatment with lead acetate recovered lead-induced reduction of flow rate but L-NAME potentiated it. Concurrent therapy of lead and L-NAME resulted in greater reduction of protein concentration when compared to that of lead. L-Arginine showed a preventive effect on lead-induced decrease of protein concentration. Both L-arginine and L-NAME prevented lead-induced reduction in calcium concentration. It is concluded that nitric oxide plays a role in salivary gland function. Also lead acetate inhibitory effect on submandibular function is somewhat diminished by L-arginine and partially increased by L-NAME. It seems that lead acetate interacts with nitric oxide modulatory role in salivary gland.

Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia.

Abstract: We have previously shown that autologous T cells recognize leukaemic cells from patients with chronic lymphocytic leukaemia (B-CLL) in an MHC class I- and/or II-restricted manner. A candidate recognition structure might be the tumour cell-derived Ig VH complementarity-determining region (CDR)3. Three patients with B-CLL were analysed for the presence of autologous T cells recognizing the tumour-specific VH-CDR3 region. The VH region was shown to be mutated in all three patients. In two patients, a VH-CDR3-specific T-cell response was detected by proliferation assay, as well as by gamma-interferon (IFN) production. The responses could be inhibited by monoclonal antibodies against MHC class II, but not MHC class I. In the third patient, a VH-CDR3 proliferative response was detected, which could be inhibited by an anti-MHC class I monoclonal antibody, but not by anti-MHC class II antibodies. No gamma-IFN response could be detected in this patient. In no patient was an interleukin (IL)-4 response noted. Thus, in patients with B-CLL, naturally occurring T cells recognizing the tumour-unique VH-CDR3 region are present.

Evaluation of workers' exposure to dust, ammonia and endotoxin in poultry industries at the province of Isfahan, Iran.

Abstract: This study was conducted to assess various environmental exposure measurements (total dust, ammonia and endotoxin) of poultry workers at the province of Isfahan, Iran. The results show that the workers who worked in enclosed systems of parent stock barns have the highest exposure to total and respirable dust: 21.3 +/- 3.2 and 4.6 +/- 0.9 mg/m3, respectively. In comparison with different ages of chicken, the highest concentration of total and respirable dust were 5.4 +/- 0.7 and 3.3 +/- 0.7 mg/m3 in the 45th day. In the above mentioned situation, the results of endotoxin concentrations were 20.6 +/- 1.1, 23.6 +/- 2.2, 21.3 +/- 1.2 and 26.8 +/- 1.8 ng/m3, respectively. Ammonia concentrations had the highest rate in enclosed systems of laying hens in winter and the 45th day of chicken age, measuring 33.2 +/- 5.2 and 20.2 +/- 3.0 mg/m3, respectively.

Isolation rates of Streptococcus pyogenes in patients with acute pharyngotonsillitis and among healthy school children in Iran.

Abstract: We examined three populations from the Tehran region and the North part of Iran (Gilan), in all more than 5000 individuals, for carriage of Streptococcus pyogenes (group A streptococci; GAS). Children or adults with acute pharyngotonsillitis and healthy school children harboured GAS in 34-1, 20.0 and 21.0%, respectively. Typing of 421 randomly selected isolates showed a predominance of M-types M4, M5, M11, M12, as well as the provisional type 4245; however, many of the isolates were T and M non-typable. Forty-three percent of all strains were opacity factor (OF) negative. The type distribution differed markedly from that reported in 1973-4, when M types 1 and 12 were predominant.

Comparison of simultaneous administration of lithium with L-NAME or L-arginine on morphine withdrawal syndrome in mice.

Abstract: Due to the claim that chronic administration of lithium or L-N(G)-nitroarginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor reduces morphine withdrawal syndrome, the effects of chronic administration of lithium, L-NAME, or L-arginine (L-Arg), a precursor of NO, alone or co-administration of lithium with L-Arg or L-NAME, on naloxone-precipitated withdrawal syndrome and physical dependence development to morphine in mice chronically treated with morphine, were evaluated. Morphine dependency was induced by the intraperitoneal injection (i.p.) of morphine (10 mg/kg), once daily for 7 days. Physical dependence to morphine was observed by precipitating an abstinence syndrome with naloxone (2 mg/kg, i.p.). Chronic administration of L-NAME (10 mg/kg, i.p., once daily, for 7 days after 10 days of receiving only tap water and food prior to naloxone), decreased all withdrawal signs significantly, while L-Arg (200 mg/kg, as above) increased only some withdrawal signs significantly in morphine-dependent mice. Chronic administration of lithium (600 mg/kg, in drinking water) alone or co-administration of lithium (as above) with L-NAME (10 mg/kg) or L-Arg (200 mg/kg, i.p., once daily) for 7 days after 10 days of receiving only lithium (as above) and food, decreased all withdrawal signs and physical dependence significantly in morphine-dependent mice. The results obtained indicate that co-administration of L-NAME with lithium increases the effect of lithium or L-NAME alone, on withdrawal signs, but this increase is not significantly different as compared to chronic lithium or L-NAME administration alone; while co-administration of L-Arg with lithium decreases the effects of lithium on withdrawal signs and this decrease is not significant as compared to chronic lithium administration alone. These findings indicate that nitric oxide may be involved in modulation of naloxone-induced withdrawal syndrome, and treatment with lithium could have some effect on this system. Copyright 2000 John Wiley & Sons, Ltd.

Subsensitivity to Opioids Is Receptor-Specific in Isolated Guinea Pig Ileum and Mouse Vas Deferens after Obstructive Cholestasis

Abstract: The rate and degree of subsensitivity development to morphine (mu-opioid receptor, preferred, but not selective agonist) and U50488H (highly selective kappa-opioid receptor agonist) were assessed in vitro on guinea pig ileum (GPI) of cholestatic animals 2, 5, and 7 days after bile duct ligation. In addition to this phenomenon of morphine, the effects of U50488H and SNC 80 (highly selective delta-opioid receptor agonist) were studied in vitro on mice vas deferens (MVD) of cholestatic animals 2, 5, 7, 10, and 15 days after bile duct ligation. The IC(50) for each compound was determined in these preparations. The ratio of the IC(50) in bile duct-ligated animals to sham and control animals provides a quantitative index for the degree of subsensitivity development to each agonist. For any given time, the highest degree of subsensitivity to morphine was observed in GPI of cholestatic animals, whereas in MVD obtained from the cholestatic animals, the highest degree of subsensitivity developed to inhibitory effect of SNC 80. The subsensitivity development in cholestatic animals was time dependent; in GPI the maximum subsensitivity developed after 7 days of the operation, whereas the maximum subsensitivity in MVD developed 15 days after bile duct ligation. Moreover, subsensitivity to exogenous acetylcholine and norepinephrine in GPI and MVD, respectively, did not develop in the presence of subsensitivity to opioids in cholestatic animals. Significant accumulation of endogenous opioids in plasma of cholestatic animals has been shown in several studies and this may account for a significant development of subsensitivity to inhibitory effects of opioid agonists.

Effect of chronic lithium administration on endothelium-dependent relaxation in rat aorta.

Abstract: 1. The effects of chronic lithium administration on the relaxant responses of rat thoracic aortic rings in the presence of indomethacin (a cyclo-oxygenase inhibitor) and/or NG-nitro-L-arginine (L-NOARG; a nitric oxide synthase inhibitor) to acetylcholine (ACh) or sodium nitroprusside were investigated in the present study. 2. Acetylcholine produced a concentration-dependent relaxation in vessels precontracted by phenylephrine (PE), while in lithium-treated rats the maximal relaxation was significantly increased. 3. Indomethacin (20 mumol/L) significantly potentiated the ACh-induced relaxation in lithium-treated and control rats. 4. NG-Nitro-L-arginine (1 mumol/L) decreased the ACh-induced relaxation in both control and lithium-treated rats. In contrast, indomethacin (20 mumol/L) reversed the inhibitory effect of L-NOARG. 5. Sodium nitroprusside produced similar concentration-dependent relaxations of vessels from both control and lithium-treated rats, which was not affected by indomethacin. In endothelium-denuded rings, indomethacin (20 mumol/L) caused a rightward shift in the concentration-contraction curve to PE. 6. These data support evidence for a possible increase in endothelium-dependent relaxation induced by ACh during long-term administration of lithium in rat aortic rings.

Transsexualism in female monozygotic twins: a case report.

Abstract: Objective: A case report is presented of a gender identity disorder involving a pair of female monozygotic twins who requested sex reassignment. As far as we know, this case is the first in psychiatric literature and supports a genetic aetiology of this disorder.Clinical picture: The patients were two 18-year-old female monozygotic twins who had showed symptoms of transsexualism since early childhood. They had no other physical or psychiatric disorder except borderline mental functioning.Treatment: The patients were referred for sex reassignment.Outcome: They were lost to follow up after initial evaluation.Conclusion: In addition to other possible (yet not confirmed) causes of trans-sexualism, a genetic basis for this disorder is suggested by this case.