Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test

Rationale: The forced swimming test (FST) is a behavioral test in rodents that predicts the clinical efficacy of many types of antidepressant treatments. Recently, a behavior sampling technique was developed that scores individual response categories, including swimming, climbing and immobility. Although all antidepressant drugs reduce immobility in the FST, at least two distinct active behavioral patterns are produced by pharmacologically selective antidepressant drugs. Serotonin-selective reuptake inhibitors increase swimming behavior, while drugs acting primarily to increase extracellular levels of norepinephrine or dopamine increase climbing behavior. Distinct patterns of active behaviors in the FST may be mediated by distinct neurotransmitters, but this has not been shown directly. Objectives: The present study examined the role of serotonin in mediating active behaviors in the forced swimming test after treatment with two antidepressant drugs, the selective serotonin reuptake inhibitor, fluoxetine and the selective norepinephrine reuptake inhibitor, desipramine. Methods: Endogenous serotonin was depleted by administering para-cholorophenylalanine (PCPA, 150 mg/kg, IP.) to rats 72 h and 48 h prior to the swim test. Fluoxetine (10 mg/kg, SC) or desipramine (10 mg/kg, SC) was given three times over a 24-h period prior to the FST. Behavioral responses, including immobility, swimming and climbing, were counted during the 5-min test. Results: Pretreatment with PCPA blocked fluoxetine-induced reduction in immobility and increase in swimming behavior during the FST. In contrast, PCPA pretreatment did not interfere with the ability of desipramine to reduce immobility and increase climbing behavior. Conclusions: Depletion of serotonin prevented the behavioral effects of the selective serotonin reuptake inhibitor fluoxetine in the rat FST. Furthermore, depletion of serotonin had no impact on the behavioral effects induced by the selective norepinephrine reuptake inhibitor, desipramine. The effects of antidepressant drugs on FST-induced immobility may be exerted by distinguishable contributions from different neurotransmitter systems. Received: 4 February 1999 / Final version: 2 June 1999     

Estrogen-induced abnormal accumulation of fat cells in the rat penis and associated loss of fertility depends upon estrogen exposure during critical period of penile development.

We previously reported that diethylstilbestrol (DES) or estradiol valerate (EV) exposure at a dose of 0.10-0.12 mg/kg, or higher, per day, on alternate days, from postnatal days 2-12, resulted in abnormal penis development and infertility (H. O. Goyal et al., 2005, J. Androl. 26, 32-43). The objective of this study was to identify a critical developmental period(s) during which EV exposure results in the observed penile abnormalities. Male pups received EV at a dose of 0.10-0.12 mg/kg on postnatal day(s) 1, 1-3, 4-6, 1-6, 7-12, 13-18, 19-24, or 25-30. Fertility was tested at 102-115 days of age and tissues were examined at 117-137 days. Both penile morphology and fertility were unaltered in rats treated with EV after 12 days of age. Conversely, except in rats treated on postnatal day 1 only, none of the males treated prior to 12 days of age sired pups, and all had abnormal penises, including varying degrees of abnormal accumulation of fat cells and loss of cavernous spaces and smooth muscle cells in the corpora cavernosa penis, which were maximal in the 1-6-day group. Also, the preputial sheath was partially released or its release was delayed, and the weight of the bulbospongiosus muscle was significantly reduced. Plasma testosterone (T) in the 1-6- and 4-6-day groups and intratesticular T in the 4-6-day group were significantly lower. The testosterone surge, characteristic of controls in the first week of life, was suppressed in the 1-3-day group. Estrogen receptor alpha mRNA expression was enhanced in the body of the penis in the 1-3-day group, but not in the 13-18-day group. Hence, EV exposure prior to 12 days of age (as short as 1-3 days postnatal), but not after 12 days of age, results in long-term abnormal penile morphology, characterized by abnormal accumulation of fat cells in the corpora cavernosa penis and, consequently, loss of fertility.     

Antesternal Colonic Interposition for Corrosive Esophageal Stricture

Restoration of swallowing in a patient with dysphagia due to nondilatable corrosive stricture of esophagus remains a surgical challenge. Organs available for replacement are stomach, jejunum, or colon. Jejunum is useful to replace a small segment, whereas stomach and colon are required for a long-segment replacement. In cases where the stomach is also injured, colon remains the only option. The route of colonic interposition has also been a subject of debate over the years. Antesternal, retrosternal, or esophageal bed passage are the routes described. In the present series, the data of antesternal colonic interposition (ACI) performed for nondilatable benign esophageal strictures in 32 patients (1988–2011) have been retrospectively analyzed. The results indicate that ACI for corrosive strictures is a quick and simple procedure. Thoracotomy is avoided and anastomosis is easily performed in the neck, and mortality rate due to anastomotic failure or graft failure is diminished. This retrospective analysis discusses the ease, effectiveness, quality of life, morbidity, and mortality of ACI and compares the pros and cons of ACI with other procedures described in the literature.     

Follow-up after coil closure of patent ductus arteriosus

A prospective serial follow-up after coil closure of patent ductus arteriosus in 84 patients showed a cumulative duct closure up to 96% at the end of 2 years. Five patients underwent transient recanalization, and 4 patients required repeat procedure for residual shunt or recanalization.     

Transcatheter coil embolization of abnormal vascular connections using a new type of delivery catheter for enhanced control

A new type of delivery catheter, designed with a 0.033-inch distal tip that grips a 0.038-inch Gianturco coil, was used to occlude 61 abnormal vascular connections in 44 patients with a complete closure rate of 87%. Withdrawal (n = 6) or repositioning (n = 2) of an inappropriately positioned coil was necessary in 8 of 44 patients, and was successfully achieved in all by the delivery catheter without need for additional equipment.     

Novel CD3Z and CD3E Deficiency in Two Unrelated Females

Journal of Clinical Immunology -     

Study of PTPN22 1858C/T polymorphism in rheumatoid arthritis patients from Western India

BackgroundRheumatoid arthritis (RA) is an inflammatory autoimmune disorder with etiologies including genetic and environmental factors. Protein tyrosine phosphatase non-receptor type22 (PTPN22) 1858C/T polymorphism is widely suspected to be a susceptibility gene for RA in the non-HLA genes group.AimThis study aimed at determining whether PTPN22 1858C/T polymorphism is associated with RA patients from Western India and to evaluate its possible association with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.MethodsA total of 130 Indian RA patients and 100 age and sex matched normal controls were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) for the PTPN22 1858C/T polymorphism.ResultsRF positivity was seen among 73.8% RA patients studied and the overall incidence of anti-CCP antibodies was 86.2%. The homozygous genotype (T/T) was absent in both groups. Among RF positives, C/C homozygosity was 90.6% whereas 9.4% patients were C/T heterozygous. Among anti-CCP positives, 89.1% had C/C genotype while the remaining 10.9% have the C/T genotype. Statistically significant association was obtained between the polymorphism and anti-CCP positivity in RA patients (OR: 2.939, ‘p’ value = 0.0595).ConclusionOur study suggested that a positive autoantibody status may predispose an individual to RA. PTPN22 may act as a susceptibility gene only in certain ethnic groups and there is no direct association between PTPN22 C1858 polymorphism and RA patients from Western India. Still a larger study is needed to understand whether this polymorphism predisposes individual to disease-associated antibodies among Indian RA patients.