An analysis of fatal adverse conditions in temporal association of COVID-19 vaccination to boost the safety of vaccination for COVID-19.

SARS-CoV-2, the causative agent of COVID-19, claimed multiple lives in a very short span of time. Seeing the urgency of situation, vaccines were developed in hitherto unseen time frame. Vaccines definitely passed the test of safety and efficacy in clinical trials, but post mass vaccination data revealed cases of fatal adverse conditions in the temporal association of vaccination. The temporal association does not guarantee that the fatality is due to vaccination, but at the same time, it does create a concern. To overcome this concern and improve the safety of vaccination, we reviewed literature and collected data of 15 studies comprising of total 22 cases of fatal adverse condition/death in the temporal association of COVID-19 vaccination. Analysis of these data shows that many persons (40.90%) who succumbed were previously healthy individuals. All those who died developed symptoms or were admitted to hospital within a period of 3 weeks after vaccination. 86.36% cases of death took place within a period of 3 weeks after vaccination/presentation/admission/intervention. Complications which lead to death were CVST, thrombocytopenia/thrombosis /VITT, DIC and haemorrhage in 81.18% of cases. 81.81% cases of death were noted in the temporal association with ChAdOx1 nCoV-19 vaccine. 68.18% persons developed symptoms after first dose. Death was more common in females (59.09%), and the most commonly affected age group was 20 to 60 years (86.36%). Knowledge of fatal adverse conditions in the temporal association of vaccination will help to tackle these situations well and improve the safety of vaccination drive further.

Treatment Options Available for COVID-19 and an Analysis on Possible Role of Combination of rhACE2, Angiotensin (1-7) and Angiotensin (1-9) as Effective Therapeutic Measure.

Corona virus disease (COVID-19), caused by SARS-CoV-2, is rapidly spreading all around the world and is posing a threat to mankind. Since SARS-CoV-2 is a novel virus, little is known about it and no effective drug is available for its treatment. While many drugs are being evaluated, an effective therapeutic measure is still lacking. SARS-CoV-2 like SARS-CoV binds with angiotensin-converting enzyme 2 (ACE2) present on human cells. SARS-CoV has been found to downregulate ACE2 and SARS- CoV-2 infection has been found to be associated with increased level of Angiotensin II. Based on these facts, we presume that SARS-CoV-2 like SARS-CoV downregulates ACE2, and in absence/reduced activity of ACE2, level of angiotensin (1-7) and angiotensin (1-9) is decreased while that of angiotensin II is increased and increased level of angiotensin II has been found to correlate with lung injury and viral load. We presume that restoration of normal functioning of renin-angiotensin system with recombinant human angiotensin-converting enzyme 2 (rhACE2), angiotensin (1-7) and angiotensin (1-9) may be an effective therapeutic measure but studies will be required to test this hypothesis and explore its possible role in treatment of COVID-19.

Carcinosarcoma of Breast Mimicking Breast Abscess.

Carcinosarcoma, a tumor having both carcinomatous and sarcomatous elements, occurring in the breast, is a rare condition. The tumor consists of both epithelial and mesenchymal cell lines and tends to behave aggressively. It has clinical features like that of invasive breast carcinoma but sometimes there can be diagnostic confusion as it can mimic or present as breast abscess. Treatment is multimodal. Surgery plays the vital role. Post-op radiation and chemo are indicated. Hormone therapy is usually inapplicable as most of the time, it is hormone receptor negative.

Nano-ropinirole for the management of Parkinsonism: blood-brain pharmacokinetics and carrier localization.

AIM: The aim of this study was to investigate the brain targeting potential of chitosan-coated oil in water nanoemulsions (CSNE(ROP)) delivered intranasally in haloperidol-induced Parkinson's disease rat models. METHODS: Chitosan-coated nanoemulsion (CSNE(ROP)) was developed through aqueous titration followed by a high pressure homogenization method. RESULTS: Gamma-scintigraphy study showed a significantly high mucoadhesive potential of CSNE(ROP) and least for conventional and homogenized formulations. Confocal study showed deep localization of formulations in the brain confirming the permeation potential of CSNE(ROP). Pharmacokinetic results of CSNE(ROP) in Wistar rat brain and plasma showed a significantly high (p** < 0.005) AUC0→24 and amplified Cmax over i.v treatment group. Neurobehavioral activity (rotarod and swim tests) and biochemical parameters (glutathion, TBARS and SOD) corroborated well with the pharmacokinetic results. The order of dopamine recovery in haloperidol-induced Wistar rats was found to be (i.n)CSNEROP group>(i.n)SolnROP group>(i.v)SolnROP group>haloperidol group. CONCLUSIONS: Finally, the investigation demonstrated that intranasal delivery of mucoadhesive nanocarrier might play as a potential candidate in the management of Parkinson's disease and related brain disorders.