Reserpine modulates neurotransmitter release to extend lifespan and alleviate age-dependent Aβ proteotoxicity in Caenorhabditis elegans

Aging is a debilitating process often associated with chronic diseases such as diabetes, cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). AD occurs at a very high incidence posing a huge burden to the society. Model organisms such as C. elegans become essential to understand aging or lifespan extension - the etiology, molecular mechanism and identification of new drugs against age associated diseases. The AD model, manifesting Aβ proteotoxicity, in C. elegans is well established and has provided valuable insights. Earlier, we have reported that Reserpine, an FDA-approved antihypertensive drug, increases C. elegans lifespan with a high quality of life and ameliorates Aβ toxicity in C. elegans. But reserpine does not seem to act through the known lifespan extension pathways or inhibition of its known target, vesicular monoamine transporter, VMAT. Reserpine's mode of action and the pathways it activates are not known. Here, we have evaluated the presynaptic neurotransmitter(s) release pathway and identified acetylcholine (ACh) as the crucial player for reserpine's action. The corroborating evidences are: i) lack of lifespan extension in the ACh loss of function (hypomorphic) - synthesis (cha-1) and transport (unc-17) mutants; ii) mitigation of chronic aldicarb effect; iii) lifespan extension in dopamine (cat-2) and dopamine and serotonin (bas-1) biosynthetic mutants; iv) no rescue from exogenous serotonin induced paralysis in the AD model worms; upon reserpine treatment. Thus, modulation of acetylcholine is essential for reserpine's action.     

Cytodiagnosis of cutaneous histoplasmosis in HIV positive patient initially presenting with multiple umbilicated disseminated skin nodules

Histoplasmosis is usually an opportunistic fungal infection in patients with defective cell mediated immunity, and has been considered as one of the acquired immunodeficiency syndrome (AIDS) defining illness. However, cutaneous involvement in human immunodeficiency virus (HIV) positive patients is less common, and very rarely can be the initial presenting symptom for the diagnosis of AIDS. We present here an unusual case of multiple diffuse cutaneous nodular lesions predominantly in face, trunk, and upper extremities diagnosed initially on aspiration cytology as histoplasmosis. Subsequent serological test revealed positivity for HIV 1 and 2, along with a low CD4 count and low CD4:CD3 ratio. The cytomorphological features were further corroborated by histology and histochemical stains. Hence, cutaneous histoplasmosis can cause multiple wide spread nodular or umbilicated lesions in AIDS patients as the initial presentation. Fine needle aspiration cytology (FNAC) is a rapid, cost effective tool for diagnosis of the fungi from such lesions and initiating work up for immunocompromised states including AIDS. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

The phenomenon of drop in output at larger field sizes for telecobalt units

It is known that the output factors (OPFs) for external-beam radiotherapy units increase with field size due to increased scattered radiation from the collimator system. Saturation in the OPF value is generally reported beyond approximately 30 × 30 cm². For the first time, to the best of our knowledge, we report on a drop in OPF values, although marginal, measured for a telecobalt machine beyond the 38 × 38 cm² field size. We believe that reporting and explaining the results will lead to a better understanding of the scatter composition of the radiation from telecobalt machines. This also has the potential to impact the estimation of low dose regions in patients, in addition to being a purely scientific inquiry. We used Monte Carlo (MC) simulations to validate the measured values. The MC data showed that the decrease in OPF was due to decreased scatter from the machine head.     

Evaluation of Preoperative Serum Levels of CA 125 and Expression of p53 in Ovarian Neoplasms: A Prospective Clinicopathological Study in a Tertiary Care Hospital

Objectives

To assess the preoperative serum levels of CA 125 with its diagnostic role and to evaluate the p53 expression in patients of primary ovarian neoplasms. We also wished to judge their relationship with other parameters like clinical staging and histopathologic tumor type.

Materials and Methods

The present study was conducted on 86 patients during the study period of 2.5 years. Preoperative CA 125 levels were evaluated by an automated immunoassay analyzer. p53 expression was judged immunohistochemically with pre-diluted monoclonal antibody. An objective scoring was done depending on distinct nuclear immunopositivity.

Results

Median value of preoperative CA 125 levels was 32 U/mL in benign surface epithelial-stromal tumors (BSEST), 53 U/mL in borderline surface epithelial-stromal tumors (BOT), 346 U/mL in malignant surface epithelial-stromal tumors (MSEST) and 560 U/mL in serous adenocarcinomas (SAC). Most of ovarian tumors were in the FIGO stage I (64 cases, 74.4%), but higher stages (II, III, IV) were observed mostly in MSESTs. SACs displayed the maximum p53 expression. Considering the cut-off value of more than 35 U/mL in CA 125 levels, the sensitivity to diagnose MSESTs was 94.7%. Preoperative CA 125 levels strongly and positively correlated with FIGO staging and p53 expression. Similarly p53 expression strongly and positively correlated with FIGO staging and histopathological categories.

Conclusion

Higher values of preoperative CA 125 levels and higher expression p53 are associated with MSESTs and BOTs especially of serous type. They strongly correlate with each other and with tumor stage. But there is no serum CA 125 concentration that can clearly differentiate benign and malignant ovarian masses.