Acute and sub acute toxicity of Amirdha Gandhi Kukkil Vallathy an effective Siddha herbo mineral formulation used in the treatment of rheumatoid arthritis in wistar albino rat model.

OBJECTIVES: Amirdha Gandhi Kukkil Vallathy (AGKV) is a herbo mineral Siddha formulation which has Sulphur, Kukkil, Seendhil and Serankottai as major ingredients and it is indicated for 80 types of Vatham diseases. Uthiravatha suronitham is one among the vatham diseases and it's clinical symptoms are correlated with Rheumatoid arthritis (RA). Since AGKV is a promising drug for RA, the safety of this drug has been validated by performing the acute and 28 days repeated oral dose toxicity study following the OECD guidelines 423 and 407. METHODS: The acute toxicity study has been performed by administering orally with a single dose of 300 and 2000 mg/kg body weight in rat models and the animals were observed for 14 consecutive days. Gross pathology was observed and animals were sacrificed at the end of the study. In 28 days repeated oral toxicity study, limit test has been carried out with a dose of 1,000 mg/kg body weight. RESULTS: No significant abnormality has been observed in the body weight, organ weight, biochemical parameters and histopathology studies. It has been revealed that this drug is safe upto 2000 mg/kg body weight in single dose study and 1,000 mg is a safer dose in the 28 days repeated oral toxicity study. CONCLUSIONS: The results of acute and 28 days repeated oral toxicity studies revealed no adverse effects in animals and hence this drug AGKV is safe and can be administered in human.

Effect of abrupt and gradual calorie restriction regimens on biochemical and behavioral markers in obese mice model.

Background: Although Calorie Restriction (CR) is primarily considered in obesity management, behavioral studies of CR and its methodology of implementation are not well-defined. Objective: The study aimed to determine the efficacy of the extensively researched method of CR-abrupt calorie restriction (ACR) and a newly proposed gradual calorie restriction (GCR) in terms of body weight, behavioral and biochemical parameters in the obese animal model-C57BL/6J mice. Design: Male obese mice were subjected to GCR regimen for 14 weeks which was compared and evaluated for anxiety-like behavior and stress levels with ACR. Plasma corticosterone was measured before initiation of CR and every three weeks following GCR and ACR, whereas plasma insulin was measured twice-after obesity induction and post 14 weeks of CR. The behavioral assessments were conducted before inducing CR and every three weeks following ACR and GCR. Results: A significant anxiety-like behavior and an increase in plasma corticosterone were observed in mice on GCR during the critical initial six weeks of CR (p < 0.05). Both groups showed a decrease in plasma glucose levels; however, the GCR group showed a significant reduction (p < 0.01). There was a significant decrease in social interaction in both groups with an increase in the latency period and a decrease in time spent with the stranger animal during the social interaction test (p < 0.05). Conclusion: The mice on GCR regimen demonstrated lesser anxiety-like behavior and low plasma corticosterone levels compared to those on ACR. This gives us a new avenue in CR research to evaluate the methodologies of implementing CR.

Is Mucormycosis an inevitable complication of Covid-19 in India?

Mucormycosis or black fungus infection is a less common disease but highly fatal infection, infecting the immunocompromised individuals. The site of predilection of the fungus is found to be lungs and brain in addition to its sequestration in sinusoidal spaces. Presently with the ongoing COVID 19 pandemic, the prevalence of this infection is found to be high in the Indian population. The fungus establishes itself by affecting the compromised immune system of an individual and thereby making the individual susceptible to other diseases/infection. The reasons attributed to the sudden upsurge are steroidal therapeutics abuse, tocilizumab therapy and diabetes mellitus.To avert the cytokine storm, the medical health workers are necessitated to include steroid drugs in COVID 19 treatment protocol however inclusion of these drugs in patients who do essentially require steroids can have their immune system debilitated and permit the invasion of this fungus. According to International Diabetes Federation (IDF), 77 million Indians are known to be diabetic, cautioning the physicians to be vigilante of the impending black fungus infection in the event of COVID19 affliction in such individuals. There is causal relationship between anti-hyperglycemic drugs and weakened immune system and opportunity for the fungus invasion. This review attempts to explain the inter-relatedness of COVID19 infection, its treatment and eventual black fungus infection risk.

The current situation of COVID-19 in India.

The COVID-19 pandemic has now risen to a global health crisis across the globe. This novel virus outbreak has challenged India's economic, medical and public health infrastructure. Health care professionals and researchers around the world are looking for an effective treatment regime for COVID-19. The number of people infected by COVID-19 in India crossed 9.74 million; nearly eleven - months after the country reported its first case. The Ministry of Health and Family Welfare of India (MOHFW) has taken numerous measures to raise awareness on COVID-19 and the necessary actions to control the spread of the virus. The central and state governments are formulating several wartime protocols to achieve this goal. The MOHFW has implemented the new clinical management protocol to treat COVID-19. Besides, the Ministry of AYUSH has also provided guidelines to use conventional preventive and treatment strategies to enhance immunity. The national recovery rate has increased to 94.66% and the reported fatality rate is down to 1.45, due to "test, track and treat". MOHFW and Ministry of AYUSH are the two pillars of health care to prevent and manage the current pandemic outbreak in India. Since, there is no specific drug or vaccine effective against COVID-19 infection, exploring every possible option for prevention and treatment is of great importance.

Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system.

Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus.