Roundup and glyphosate's impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans.

As 3 billion pounds of herbicides are sprayed over farmlands every year, it is essential to advance our understanding how pesticides may influence neurological health and physiology of both humans and other animals. Studies are often one-dimensional as the majority examine glyphosate by itself. Farmers and the public use commercial products, like Roundup, containing a myriad of chemicals in addition to glyphosate. Currently, there are no neurological targets proposed for glyphosate and little comparison to Roundup. To investigate this, we compared how glyphosate and Roundup affect convulsant behavior in C. elegans and found that glyphosate and Roundup increased seizure-like behavior. Key to our initial hypothesis, we found that treatment with an antiepileptic drug rescued the prolonged convulsions. We also discovered over a third of nematodes exposed to Roundup did not recover from their convulsions, but drug treatment resulted in full recovery. Notably, these effects were found at concentrations that are 1,000-fold dilutions of previous findings of neurotoxicity, using over 300-fold less herbicide than the lowest concentration recommended for consumer use. Exploring mechanisms behind our observations, we found significant evidence that glyphosate targets GABA-A receptors. Pharmacological experiments which paired subeffective dosages of glyphosate and a GABA-A antagonist yielded a 24% increase in non-recovery compared to the antagonist alone. GABA mutant strain experiments showed no effect in a GABA-A depleted strain, but a significant, increased effect in a glutamic acid decarboxylase depleted strain. Our findings characterize glyphosate's exacerbation of convulsions and propose the GABA-A receptor as a neurological target for the observed physiological changes. It also highlights glyphosate's potential to dysregulate inhibitory neurological circuits.

Discovery and development of azasteroids as anticancer agents.

Cancer is the second leading cause of death worldwide following cardiovascular diseases. Cancer can be treated by a variety of techniques including surgery, radiation therapy, immunotherapy, and chemotherapy. Choice of the method can be made based on type, physiologic location and the stage of disease progression. Among chemical methods, steroids find broad applications. Azasteroids have N- substitutions in steroidal rings. This structural modification renders azasteroids advantageous in increased effectiveness and reduced side effects. Numerous accounts of cancer efficacy of this family of compounds are available in literature. The progress made in the discovery, synthetic efforts and development of azasteroids as anticancer agents is broadly outlined in this review.

A Comparative Study of RIPASA Score and ALVARADO Score in the Diagnosis of Acute Appendicitis.

BACKGROUND: Acute appendicitis is one of the most common surgical emergencies. Different techniques have been devised to assist in equivocal cases in attempts to decrease negative appendicectomy rates. A number of scoring systems have been used for aiding in early diagnosis of acute appendicitis and its prompt management of which Alvarado score is the most popular. The accuracy of Alvarado score in the diagnosis of acute appendicitis is disappointingly low in Asian population and RIPASA scoring has been designed for the diagnosis of acute appendicitis in the Asian population. So we prospectively applied and compared Alvarado and RIPASA score in the diagnosis of acute appendicitis in Indian population. MATERIALS AND METHODS: We compared prospectively RIPASA and Alvarado scoring system by applying them to 206 patients. Both scores were calculated for patients who presented with right iliac fossa pain during the study period. Depending on clinical judgment appendicectomy was done. Post operative histopathology report was correlated with the scores. A score of 7.5 is the optimal cut off threshold for RIPASA and 7 for Alvarado scoring system. Sensitivity, specificity, positive predictive value (PPV) and negative predictive (NPV) for RIPASA & Alvarado system was done. RESULTS: The sensitivity and specificity of RIPASA score were 96.2% and 90.5% respectively. The sensitivity and specificity of Alvarado score were 58.9% and 85.7% respectively. RIPASA score correctly classified 96 percent of all patients confirmed with histological acute appendicitis to the high probability group (RIPASA score greater than 7.5) compared with 58.9% with Alvarado score (Alvarado score greater than 7.0; p-value less than 0.001). CONCLUSION: RIPASA scoring system is more convenient, accurate, and specific scoring system for Indian population than Alvarado scoring system.