Suppression of inhibitory GABAergic transmission by cAMP signaling pathway: alterations in learning and memory mutants

The cAMP signaling pathway mediates synaptic plasticity and is essential for memory formation in both vertebrates and invertebrates. In the fruit fly Drosophila melanogaster, mutations in the cAMP pathway lead to impaired olfactory learning. These mutant genes are preferentially expressed in the mushroom body (MB), an anatomical structure essential for learning. While cAMP‐mediated synaptic plasticity is known to be involved in facilitation at the excitatory synapses, little is known about its function in GABAergic synaptic plasticity and learning. In this study, using whole‐cell patch‐clamp techniques on Drosophila primary neuronal cultures, we demonstrate that focal application of an adenylate cyclase activator forskolin (FSK) suppressed inhibitory GABAergic postsynaptic currents (IPSCs). We observed a dual regulatory role of FSK on GABAergic transmission, where it increases overall excitability at GABAergic synapses, while simultaneously acting on postsynaptic GABA receptors to suppress GABAergic IPSCs. Further, we show that cAMP decreased GABAergic IPSCs in a PKA‐dependent manner through a postsynaptic mechanism. PKA acts through the modulation of ionotropic GABA receptor sensitivity to the neurotransmitter GABA. This regulation of GABAergic IPSCs is altered in the cAMP pathway and short‐term memory mutants dunce and rutabaga, with both showing altered GABA receptor sensitivity. Interestingly, this effect is also conserved in the MB neurons of both these mutants. Thus, our study suggests that alterations in cAMP‐mediated GABAergic plasticity, particularly in the MB neurons of cAMP mutants, account for their defects in olfactory learning.     

Effect of sleeve gastrectomy bariatric surgery-induced weight loss on serum AMH levels in reproductive aged women

Objective: This study aims to evaluate the change in serum anti-Mullerian hormone (AMH) levels in patients with morbid obesity undergoing bariatric surgery for weight loss.

Material and methods: In this prospective observational study, 75 patients of reproductive age (20–35 years) undergoing bariatric surgery for morbid obesity were followed up after six months to determine the changes in weight, Body Mass Index (BMI), menstrual pattern and serum AMH. The results were further studied on basis of pre operative classification of patients in polycystic ovary syndrome (PCOS) and non-PCOS group.

Result: The serum AMH levels were statistically higher in patients of PCOS group pre operatively and at the end of six months in comparison to non-PCOS patients. The AMH values reduced post operatively in both groups significantly so much in the values though not significant statistically. Non-PCOS patients had lower AMH values pre operatively and showed a trend towards reducing ovarian reserve after six months. The overall change in AMH values in both groups was statistically significant as was the normalization of menstrual irregularity.

Conclusion: Morbidly obese patients with PCOS appear to benefit from bariatric surgery both in terms of regularization of menstrual function and normalization of serum AMH values.     

Leishmania donovani-induced ceramide as the key mediator of Akt dephosphorylation in murine macrophages: role of protein kinase Czeta and phosphatase

Leishmania donovani is an intracellular protozoan parasite that impairs the host macrophage immune response to render it suitable for its survival and establishment. L. donovani-induced immunosuppression and alteration of host cell signaling is mediated by ceramide, a pleiotropic second messenger playing an important role in regulation of several kinases, including mitogen-activated protein kinase and phosphatases. We observed that the endogenous ceramide generated during leishmanial infection led to the dephosphorylation of protein kinase B (PKB) (Akt) in infected cells. The study of ceramide-mediated Akt phosphorylation revealed that Akt was dephosphorylated at both Thr308 and Ser473 sites in infected cells. Further investigation demonstrated that ceramide was also responsible for the induction of PKCzeta, an atypical Ca-independent stress kinase, as well as the ceramide-activated protein phosphatases (e.g., protein phosphatase 2A [PP2A]). We found that Akt dephosphorylation was mediated by ceramide-induced PKCzeta-Akt association and PP2A activation. In addition, treatment of L. donovani-infected macrophages with PKCzeta-specific inhibitor peptide could restore the translocation of phosphorylated Akt to the cell membrane. This study also revealed that ceramide is involved in the inhibition of proinflammatory cytokine tumor necrosis factor alpha release by infected macrophages. These observations strongly suggest the importance of ceramide in the alteration of normal cellular functions, impairment of the kinase/phosphatase balance, and thereby establishment of leishmaniasis in the hostile macrophage environment.     

Revisional Surgery or Pharmacotherapy for Insufficient Weight Loss and Weight Regain After Primary Bariatric Procedure: a Descriptive Study

Obesity Surgery - Bariatric surgery is the most effective and durable treatment option for clinically severe obesity. Unfortunately, some degree of weight regain (WR) is common after nadir weight...     

Intestinal Ischemia After Allogeneic Stem Cell Transplantation: A Report of Four Cases

Gastrointestinal ischemia after allogeneic bone marrow transplantation is a rare complication not well-described in the literature. Herein we retrospectively review charts of four patients who developed intestinal ischemia after allogeneic bone marrow transplantation at our institution. The patients were found to be predominately younger males who presented with nonspecific abdominal pain. Graft-versus-host disease was a common finding among all patients. Laboratory values suggestive of microangiopathy were present in two patients. Obesity and hypertriglyceridemia were cardiovascular risk factors found in these patients. The development of thrombotic microangiopathy and cardiovascular risk factors after allogeneic bone marrow transplantation may predispose patients to gastrointestinal ischemia and may portend a poor prognosis.     

Atypical Femoral Fractures: Transverse Morphology at Lateral Cortex Is a Critical Feature

In 2010, the American Society for Bone and Mineral Research (ASBMR) task force defined major and minor features to assist in the case finding and reporting of atypical femoral fractures (AFFs). One major feature that was proposed was a “transverse or short oblique configuration.” Our primary aim was to compare the conventional overall fracture morphology (OFM) with its associated angle (OFMA) and our proposed lateral cortical fracture angle (LCFA) in the assessment of fracture configuration in suspected AFFs and non‐AFFs. The radiographs of 79 patients with AFFs and 39 patients with non‐AFFs were each analyzed by two blinded reviewers to obtain the OFM, OFMA, and LCFA. Using the overall fracture morphology to assess the suspected AFFs resulted in discordance between reviewers in 18 cases (22.8%), of which 5 (6.3%) were discordant between short oblique (>30° to 60°) and long oblique (>60° to 90°) configurations, therefore affecting their classifications as AFFs. By assessing only the critical component within the lateral cortex, all the suspected AFFs fell well within the classification as transverse fractures with a mean LCFA of 4.8° (range 0.3 to 18.0, SD = 4.23). The inter‐reader variability was also lower for LCFA versus OFMA (4.1° versus 6.9°, p = 0.001) when used to assess AFFs. Fracture angles were significantly different in AFFs versus non‐AFFs regardless of whether the OFMA or LCFA methodology was employed, but the greater difference associated with LCFA suggests its greater discriminating power. When LCFA was used in conjunction with 0° to 30° as the criteria for transverse morphology, all the AFFs and non‐AFFs were correctly classified. By using a standardized and precise method in measuring the fracture angle, specifically using only the component of the lateral cortex and limiting to truly transverse fractures, ie, between 0° and 30°, the LCFA is a robust and accurate method to assess the fracture morphology in suspected AFFs. © 2014 American Society for Bone and Mineral Research.     

Laboratory evaluation of some larvicidal agents against Anopheles culicifacies in Pune.

A laboratory study to evaluate some larvicidal agents against Anopheles culcifacies was carried out. The findings of this study brought out that the larvae of this species were highly susceptible to temephos, fenthion, Paris green and Mosquito Larvicidal Oil (MLO) in that order. The LC50 values in respect of these larvicides were 0.0009 ppm, 0.0081 ppm, 0.029 ppm and 0.015 ml respectively and LC90 values were 0.0018 ppm, 0.022 ppm, 0.11 ppm and 0.046 ml respectively.