Early metabolomics changes in heart and plasma during chronic doxorubicin treatment in B6C3F1 mice

The present study aimed to identify molecular markers of early stages of cardiotoxicity induced by a potent chemotherapeutic agent, doxorubicin (DOX). Male B6C3F₁ mice were dosed with 3 mg kg^?1 DOX or saline via tail vein weekly for 2, 3, 4, 6 or 8 weeks (cumulative DOX doses of 6, 9, 12, 18 or 24 mg kg^?1, respectively) and euthanized a week after the last dose. Mass spectrometry‐based and nuclear magnetic resonance spectrometry‐based metabolic profiling were employed to identify initial biomarkers of cardiotoxicity before myocardial injury and cardiac pathology, which were not noted until after the 18 and 24 mg kg^?1 cumulative doses, respectively. After a cumulative dose of 6 mg kg^?1, 18 amino acids and four biogenic amines (acetylornithine, kynurenine, putrescine and serotonin) were significantly increased in cardiac tissue; 16 amino acids and two biogenic amines (acetylornithine and hydroxyproline) were significantly altered in plasma. In addition, 16 acylcarnitines were significantly increased in plasma and five were significantly decreased in cardiac tissue compared to saline‐treated controls. Plasma lactate and succinate, involved in the Krebs cycle, were significantly altered after a cumulative dose of 6 mg kg^?1. A few metabolites remained altered at higher cumulative DOX doses, which could partly indicate a transition from injury processes at 2 weeks to repair processes with additional injury happening concurrently before myocardial injury at 8 weeks. These altered metabolic profiles in mouse heart and plasma during the initial stages of injury progression due to DOX treatment may suggest these metabolites as candidate early biomarkers of cardiotoxicity. Published 2016. This article is a U.S. Government work and is in the public domain in the USA     

Emerging trends of Nipah virus: A review

Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats‐to‐human and human‐to‐human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.     

Towards high-throughput phenotyping of complex patterned behaviors in rodents: focus on mouse self-grooming and its sequencing

Increasingly recognized in biological psychiatry, rodent self-grooming is a complex patterned behavior with evolutionarily conserved cephalo-caudal progression. While grooming is traditionally assessed by the latency, frequency and duration, its sequencing represents another important domain sensitive to various experimental manipulations. Such behavioral complexity requires novel objective approaches to quantify rodent grooming, in addition to time-consuming and highly variable manual observation. The present study combined modern behavior-recognition video-tracking technologies (CleverSys, Inc.) with manual observation to characterize in-depth spontaneous (novelty-induced) and artificial (water-induced) self-grooming in adult male C57BL/6J mice. We specifically focused on individual episodes of grooming (paw licking, head washing, body/leg washing, and tail/genital grooming), their duration and transitions between episodes. Overall, the frequency, duration and transitions detected using the automated approach significantly correlated with manual observations (R = 0.51-0.7, p < 0.001-0.05). This data validates the software-based detection of grooming, also indicating that behavior-recognition tools can be applied to characterize both the amount and sequential organization (patterning) of rodent grooming. Together with further refinement and methodological advancement, this approach will foster high-throughput neurophenotyping of grooming, with multiple applications in drug screening and testing of genetically modified animals.     

Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence

Behavioral and Psychological Symptoms of Dementia (BPSD) are increasingly recognized as a major risk factor for caregiver burden, institutionalization, greater impairment in activities of daily living (ADLs), more rapid cognitive decline, and a poorer quality of life. BPSD contribute significantly to the direct and indirect costs of caring for patients with dementia even after adjusting for the severity of cognitive impairment and other co-morbidities. Research on these symptoms has indicated a complex interplay between the biological, psychological and social factors involved in the disease process. Although some psychotropic medications have shown modest efficacy in the treatment of these behaviors, their use has generated controversy due to increasing recognition of the side effects of these medications especially the antipsychotic medications. In this review, we examine the risk of cerebrovascular adverse events (CVAEs) and death with antipsychotic medications when used to treat elderly patients with dementia.     

Hand, foot and mouth disease in Nagpur

Hand, foot and mouth disease (HFMD) is a viral infection of children caused by Coxsackie virus-A16, a type of enterovirus closely related with the virus that causes herpangina. Although seen worldwide, it is not common in India. Hand, foot and mouth disease is sporadically reported from India as a mild illness. This report describes four cases of HFMD from Nagpur, Central India, seen between September 2005 and April 2006. All patients presented with a mild febrile prodrome followed by the appearance of aphthous-like oral ulcers and vesicular lesions on the hands and feet. All cases were clinically diagnosed. Coxsackie virus A16 was isolated from the serum of one of the patients. All the patients were in the age group of 3-5 years from different schools. It was a mild illness and all the four patients recovered without any complication. There were no secondary cases in the families.     

Premature ovarian failure due to cyclophosphamide: a report of four cases in dermatology practice

Immunosuppressant drugs like cyclophosphamide are used in the treatment of a variety of skin disorders. Though it is a very useful drug, it has some serious side-effects. Prolonged amenorrhea due to premature ovarian failure leading to infertility is one of the serious side-effects of cyclophosphamide. Four cases of cyclophosphamide-induced premature ovarian failure are presented. Two patients of scleroderma, one patient of pemphigus and one patient of hypersensitivity vasculitis developed amenorrhea due to premature ovarian failure leading to infertility after receiving cyclophosphamide 50 mg o.d. for eight months to one year. The ages of these patients ranged from 28-38 years. All these patients had good improvement of their disease with cyclophosphamide. These patients did not experience any other side-effects and their routine blood and urine tests were normal. There were no spontaneous menses during the follow-up period of one to two years. Because of the serious risk of developing premature ovarian failure, cyclophosphamide should be avoided in those patients where the family is not complete.     

RTehvieew impact of antiretroviral therapy on HPV andcervical intraepithelial neoplasia: current evidence and directions for future research

Increasing numbers of human immunodeficiency virus (HIV)-infected women are now accessing life-prolonging highly active antiretroviral therapy (HAART) in developing countries. There is a need for better understanding of interactions of human papillomavirus (HPV) and HIV, especially in the context of increasing life expectancy due to HAART. The data regarding the impact of HAART on reducing the incidence and progression and facilitating the regression of HPV infection and cervical abnormalities is largely inconsistent. Published studies differ in their study designs (prospective or retrospective cohorts or record linkage studies), screening and diagnostic protocols, duration and type of HAART use, recruitment and referral strategies, and definitions of screening test and disease positivity. Due to the ethical and resource limitations in conducting randomized trials of the impact of HAART on incidence of HPV, CIN, and cervical cancer among HIV-infected women, it is important to consider innovative study designs, including quasi-experimental trials and operations research in sentinel populations to answer the critical research questions in this area.