Effects of nitric oxide modulators and antioxidants on endocrine and cellular markers of acute stress in rats.

The effects of nitric oxide modulators (NO-modulators) and antioxidants on acute (RSx1) restraint stress induced endocrine, cellular and oxidative/nitrosative stress markers was studied in Wistar rats. The results of our study revealed that exposure to RS(x1) enhanced malondialdehyde (MDA), heat shock protein (HSP-70), corticosterone, nuclear factor kappa B (NF-κB) levels and suppressed glutathione (GSH), superoxide dismutase (SOD) and total nitrites and nitrates (NOx) levels. NO precursor and NO synthase inhibitors were found to differentially modulate stress mechanisms, by altering NF-κB, HSP-70 and corticosterone levels. l-Ascorbic acid significantly suppressed acute stress induced elevation of NF-κB and HSP-70 levels depicting protective effects, as also evidenced by reversal of elevated plasma corticosterone levels. Therefore, modulation of oxidative and nitrosative pathways, offers an approach in modulating stress induced changes associated with various disorders.

Treatment and disposal practices of pharmaceutical effluent containing potential antibiotic residues in two states in India and perceptions of various stakeholders on contribution of pharmaceutical effluent to antimicrobial resistance: a qualitative study.

BACKGROUND: Antimicrobial resistance (AMR) is a looming pandemic, demanding prompt actions to avert catastrophic consequences. Effluents from pharmaceutical industries containing antimicrobial residues could serve as one of the entry points of these drugs to the environment. This qualitative study explores the treatment and disposal practices of pharmaceutical effluent (PE) containing potential antibiotic residues (ARs) by interviewing major stakeholders. In addition, we assessed their knowledge and perception on contribution of PE to AMR. METHODS: The study was conducted in the two Indian states, Haryana and Telangana and at the federal level. Data was collected by semi-structured in-depth interviews of 29 participants from 17 stakeholders/organizations viz. Central Pollution Control Board (CPCB), State Pollution Control Boards (SPCBs) of Telangana and Haryana, civic body, pharmaceutical manufacturers, pharmaceutical associations and civil society. Data was analyzed using thematic analysis. RESULTS: The effluent treatment and disposal practices varied with the multinational companies (MNCs) having advanced technologies whereas the small and medium-scale pharmaceutical companies (SMPCs) having effluent treatment plants as per the regulations but often under-utilized. The presence of ARs in the PE was considered inconsequential by SPCBs and SMPCs and majority of stakeholders imputed other causes as major contributors to AMR. However, the MNCs were well aware of the contribution of PE to AMR and CPCB also considered ARs as direct source of AMR. The central regulators as well as MNCs expressed concerns regarding the current regulations lacking maximum ARs in the PE. CONCLUSION: Setting up regulatory standards for maximum ARs in PE, their implementation and monitoring is an urgent need to curb environmental contribution of ARs to AMR. The findings of our study will help in systematic approach in policy making, awareness programs and capacity-building in dealing with the ARs in PE to combat AMR.

Brain Uptake of Neurotherapeutics after Intranasal versus Intraperitoneal Delivery in Mice.

There is a growing global prevalence of neurodegenerative diseases such as Alzheimer's disease and dementia. Current treatment for neurodegenerative diseases is limited due to the blood brain barrier's ability to restrict the entry of therapeutics to the brain. In that context, direct delivery of drugs from nose to brain has gained emerging interest as an important alternative to oral and parenteral routes of administration. Although there are considerable reports showing promising results after intranasal drug delivery in various disease-models and investigatory human clinical trials, there are very few studies showing a detailed pharmacokinetics with regard to the uptake and retention of intranasally delivered material(s) within specific brain regions, which are critical determining factors for dosing conditions and optimal treatment regimen. This investigation compared a time-dependent brain uptake and resident time of various radiolabeled candidate neurotherapeutics after a single bolus intranasal or intraperitoneal administration in mice. Results indicate that the brain uptake of intranasally delivered therapeutic(s) is > 5 times greater than that after intraperitoneal delivery. The peak uptake and resident time of all intranasally delivered test therapeutics for all brain regions is observed to be between 30min-12h, depending upon the distance of brain region from the site of administration, followed by gradual fading of radioactive counts by 24h post intranasal administration. Current study confirms the usefulness of intranasal administration as a non- invasive and efficient means of delivering therapeutics to the brain to treat neurodegenerative diseases including Alzheimer's disease.

Anti-edema effects of rhEpo in experimental traumatic brain injury.

PURPOSE: Traumatic brain injury (TBI) is one of the leading causes of disability and death which begins with the formation of edema as the persistent primary causative factor in TBI. Although medical management of cerebral edema by hypothermia, ventriculostomy, mannitol or hypertonic saline have been effective in treating edema, many of these therapies end up with some neurologic deficits, necessitating novel treatment options for treating post-TBI edema. This study investigated edema reducing effects of recombinant human Erythropoietin (rhEPO) in reducing acute brain edema in the CCI mouse model of TBI. METHODS: Anti-edema effects of rhEpo in reducing acute brain edema after injury in the CCI mouse model of TBI were assessed by T2 weighted magnetic resonance imaging (T2wMRI) as the accurate detector of brain edema in correlation with Western blot analysis of cerebral aquaporin 4 (AQP4) index as the critical marker of edema. RESULTS: Results show that rhEpo treatment significantly reduced brain edema with concomitant reduction in AQP4 immunoexpression in the CCI mouse model of TBI. CONCLUSION: Current results emphasize clinical utility of rhEpo in treating post-TBI edema.