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Background: Negative geotaxis (NG) is an important parameter, commonly used in study of different CNS diseases and neurodevelopmental disorders. Neurobehavioural change following brain injury was easily identified by negative geotaxis. Purpose: Although NG is evaluated in the settings of ASD, most of the studies are conducted for short duration (1-3 day) and the overall trend of acquisition of NG is not evaluated. In this context, we wanted to evaluate the trend of acquisition of negative geotaxis as a behavioural marker of autism in Valproic acid (VPA) model of ASD. Methods: Dams in the VPA group were treated with intraperitoneal injections of VPA 600 mg/kg single dose on gestational day 12.5, while the control animals received normal saline of similar volume. Developmental parameters {body weight (PND 8, 10 & 12), body length (PND 4, 5, 6 8, 10), eye opening (PND 10, 12, 14, 15 and 16) and motor development (grid walking test on PND 20)} were monitored. Negative geotaxis test was performed at PND 6, 10, 15 and 17. Results: The results of the present experiments demonstrate that VPA exposed rats exhibited delayed developmental parameters, aberration of the pattern of acquisition of negative geotaxis, enhanced negative geotaxis in early postnatal period (PND 6) and enhanced negative geotaxis in absence of visual clues (PND 17). Conclusion: NG can be a valuable biomarker in early detection of autistic behavior and in absence of visual clues. The abberant negative geotaxis developmental pattern can serve as a marker to detect ASD. Thus NG can serve as an important early age biomarker of ASD. Further studies are required to validate this finding.

Metabolomics is an upcoming technology system which involves detailed experimental analysis of metabolic profiles. Due to its diverse applications in preclinical and clinical research, it became an useful tool for the drug discovery and drug development process. This review covers the brief outline about the instrumentation and interpretation of metabolic profiles. The applications of metabolomics have a considerable scope in the pharmaceutical industry, almost at each step from drug discovery to clinical development. These include finding drug target, potential safety and efficacy biomarkers and mechanisms of drug action, the validation of preclinical experimental models against human disease profiles, and the discovery of clinical safety and efficacy biomarkers. As we all know, nowadays the drug discovery and development process is a very expensive, and risky business. Failures at any stage of drug discovery and development process cost millions of dollars to the companies. Some of these failures or the associated risks could be prevented or minimized if there were better ways of drug screening, drug toxicity profiling and monitoring adverse drug reactions. Metabolomics potentially offers an effective route to address all the issues associated with the drug discovery and development.

Review Article IntRoductIonVariceal bleeding and hepatorenal syndrome (HRS) often complicate advanced liver disease. Earlier vasopressin was used for the treatment of HRS and variceal bleeding, but it had moderate efficacy and was associated with high rate of ischemic adverse effects. [1] Terlipressin, introduced in the early 1990s, is a synthetic analog of vasopressin with fewer side effects and longer duration of action. [2] Terlipressin is recommended for the management of both the conditions. [2][3][4] Ischemia leading to gangrene is a relatively rare adverse effect of terlipressin. In this context, we reviewed all the published case reports of terlipressin-induced ischemic complications. This is the first review of this kind for evaluation of different terlipressin associated ischemic complications, management strategies, and their outcome. Search strategyWe used different permutations and combinations of keywords "terlipressin," "ischemia," "gangrene," "necrosis," "infarction," "case report," and "report" for searching different databases such as PubMed, Embase, Google Scholar, and Cochrane database (till July 22, 2016). In addition, we also searched references of the studies of screened articles to extract information about relevant articles. Study selectionIn the first step, titles and abstracts of the articles were reviewed and irrelevant articles were excluded. In the next step, full texts of the selected articles were screened as per inclusion and exclusion criteria.Inclusion criteria -(a) patients: any age group and both genders, (b) intervention: terlipression, and (c) type of study: case report. Exclusion criteria: articles with an outcome other than ischemic event were excluded from the study. Data extractionThe first two authors independently extracted the data. In case of any discrepancy, the last and the penultimate authors were consulted Terlipressin is used in the management of variceal bleeding and hepatorenal syndrome. Ischemic complications are rare, but serious adverse effects of terlipressin therapy can be fatal. In this context, we reviewed all the published case reports of terlipressin-induced ischemic complications, and data were collected regarding the part of body affected by ischemic complication, latency, geographical variation, different treatment strategies and their outcome, and other relevant information. After an exhaustive search in different databases, 33 published cases were found. The ischemic complications affected virtually every part of the body. Peripheral gangrene was the most common ischemic complication followed by ischemic complications of more proximal parts such as thigh and abdominal wall. Other parts affected were heart, colon, small intestine, scrotum, etc. Most cases were managed conservatively. Although in few cases, other treatment options were also explored, knowledge of this dreaded complication and different management strategies is necessary for early identification of this adverse effect and early management so as to prevent fatality.

Construct, face and predictive validities are necessary for any disease model. Although rodent models are used to investigate the neurobiology of autism, however, till date there is no such ideal animal model which can fulfill all the above said validities. Available drug therapy to treat autism is very limited and less effective. In this review, we summarize the work done with rodent models of autism and highlight different validities. We found that, very few studies have studied all the validities in a single study and none of the study fulfilled all the validities. We also reviewed the drugs used in the treatment of autism. Here we propose the limitations of available animal models. We also propose the urgent need of additional models to fulfill all the validities and to understand autism in a better way.