Safe and effective dosage combination of purple sweet potato extract and red fruit oil extract as antioxidant and hypolipidemic in rats given high cholesterol feed
The COVID-19 pandemic has impacted not only our physical health, but also our mental wellbeing, leaving long-lasting scars that time might heal.Antidepressants are known to alleviate stress, anxiety, and depression by modulating specific neurotransmitters that are associated with these conditions, which aid in communication between brain cells, and each antidepressant acts on these neurotransmitters in slightly different ways, making them a popular treatment choice.We describe in this prospective longitudinal observational study ten COVID-19-positive cases with severe disease symptoms and post-infection mental scars, who were prescribed fluoxetine and paroxetine.These treated cases experienced a progressive reduction of illness severity and anxiety upheaval surrounding this pandemic, which may involve the negative action of stress on COVID-19 patients and the positive action of antidepressants against the viral disease.Effective treatments of COVID-19, especially those that are easy to use, show good tolerability, and have widespread availability at low cost, with their less bothersome effects and non-addictive properties should be widely studied.
The purpose of this study is to identify the cholinergic receptor subtype that mediates the peripheral antinociceptive effect of acetylcholine.To induce hyperalgesia, rat paws were treated with intraplantar prostaglandin E 2 (PGE 2 , 2 μg).The nociceptive thresholds to pressure (grams) were measured by paw flexion reaction using an algesimeter apparatus 3 h following injection.Intraplantar administration of acetylcholine (ACh; 50, 100, 200 and 400 μg) caused dose-dependent antinociception in PGE 2induced hyperalgesia.The subtype-selective muscarinic receptor antagonists for M 1 (telenzepine; 3, 6 and 12 μg), M 2 (dimethindene; 40 and 80 μg), M 3 (4-DAMP, 40 and 80 μg), and M 4 (tropicamide; 40 and 80 μg) as well as the nicotinic antagonist (mecamylamine; 25, 50 and 100 μg) were all co-administered with acetylcholine (200 μg).Only telenzepine and mecamylamine antagonized the antinociceptive effect of ACh.These data suggest the presence of M 1 and nicotinic cholinergic receptors at the peripheral level and that exogenous acetylcholine induces receptor activation with consequent antinociception.
Loads of medications and vaccines are under investigation to prevent and heal coronavirus disease 2019 (COVID-19), which is putting a strain on healthcare systems worldwide. Among them, therapy with neutralizing monoclonal antibodies (nAbs) seems to be very promising in halting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the illness and in providing the patients with passive immunity. NAbs are designed to mimic the body’s natural immune response. Coronavirus infection is mediated by the interplay between the viral spike and the tissue angiotensin-converting enzyme 2 (ACE 2) receptor found on the apical surface of numerous cell types. However, nAbs are capable of blocking this interaction. They bind to the spike protein, thus impeding SARS-CoV-2 to enter human cells and tagging it for destruction. NAbs can be crucial in preventing COVID-19 from progressing to a severe form, and potentially are a prophylaxis option to subjects who have been exposed to SARS-CoV-2, while still waiting to get a vaccine. This mini review provides the readers with an overview about what is already known and what is new about the use of these agents. © 2021, Research Trends (P) LTD.. All rights reserved.
The inflammatory bowel disease (IBD) is a multifactorial disorder and complex. Previous studies have shown that Cleistocalyx operculatus Roxb. Merr. et Perry and Morus alba L. have anti-inflammatory properties. This study aims to evaluate the effects of combined Cleistocalyx operculatus Roxb. Merr. et Perry and Morus alba L. ( CM ) extracts on dextran sulfate sodium (DSS)-induced acute colitis in mice. The combined Cleistocalyx operculatus Roxb. Merr. et Perry and Morus alba L. leaves were extracted with 50% ethanol and then suspended in water and partitioned successively with ether and ethyl acetate. The ethyl acetate extract was combined and evaporated to obtain CM extract. Mice were induced colitis, by using DSS for seven days. Mice were treated with combined CM extracts at doses of 150 mg/kg/b.w. and 300 mg/kg/b.w. Throughout the experiment, the disease activity index (DAI) was evaluated. Following the last day of treatment, blood samples were collected for analysis of IL-1 β , INF- γ and TNF- α by using a sandwich enzyme-linked immunosorbent assay (ELISA) method. The CM extract significantly decreased the disease activity index and myeloperoxidase activity in the CM extract-treated mice as compared with DSS group mice. The combined CM extracts also suppressed the levels of pro-inflammatory IL-1 β , INF- γ and TNF- α in colon tissues of the CM extract-treated mice as compared with DSS group (p < 0.05). Our results showed that the combined CM extract has strong beneficial effects on colitis and could be used for the treatment of IBD.
Depression is one of the leading causes of disease burden globally. Over the past 6 decades we have seen a multitude of antidepressants from different classes. Vilazodone is a novel antidepressant with the combination of serotonin reuptake inhibition and 5HT1A partial agonism. We wished to study its efficacy and safety in comparison to fluoxetine, in the Indian population. This is a 6-week prospective randomized open label comparative study of efficacy and safety of vilazodone and fluoxetine in patients with major depressive disorder. We recruited 72 subjects and 66 completed the study. We rated the overall severity and improvement in psychopathology by using CGI-S and CGI-I, respectively on three occasions, i.e. day 1, week 3 and week 6. We also recorded and compared the side effects of study medication with the checklist from the vilazodone prescribing information, during week 3 and 6. We compared the efficacy data using independent t test and repeated measures analysis of variance (ANOVA), and side effects using Pearson Chi-Square test. The socio-demographic data was evenly distributed except for literacy, which was significantly better in the vilazodone group. There was no significant difference in the efficacy of fluoxetine and vilazodone both at week 3 and week 6. However patients on vilazodone reported significantly higher gastrointestinal side effects. The efficacy of vilazodone is comparable to fluoxetine in the Indian population in the shortterm treatment of depression, though associated with frequent gastrointestinal side effects. We need further blinded studies on long term efficacy and safety, with a larger sample size to generalize the results.
Diabetes mellitus has become a pandemic and a predominant health problem due to its rapid and increased prevalence in developed and developing countries. Diabetes is a metabolic disorder characterised by hyperglycaemia. The increase in glucose level is due to inappropriate secretion or action of insulin. Diabetes has produced a significant impact on morbidity and mortality rate. The various complications produced due to chronic diabetes include retinopathy, nephropathy and neuropathy. The major health problem includes occurrence of macrovascular complications like coronary artery diseases. Long-standing poor glycemic control results in hyperlipidemia, hypertension and obesity. This prospective, observational and cross-sectional study was undertaken as a short time project for a period of 3 months (December 2018-February 2019 by a second year MBBS student. The study was conducted in the Outpatient Department of Medicine by the Department of Pharmacology. The study was initiated after obtaining approval from the human ethics committee and from the patients by voluntary consent. Around 150 patients who were confirmed with type 2 diabetes were selected to be part of the study. The patients were grouped according to their HbA1c levels (7-8%, 8-10% and above 10%) and each group had 50 patients. Total cholesterol (TC), triglycerides (TGL), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), fasting blood glucose and postprandial blood glucose were measured in these patients. The present study confirmed elevation in lipid parameters with rise of HbA1c levels. Thus, the study clearly identified the need for early diagnosis of lipid levels in type 2 diabetes in order to prescribe suitable drugs by which further cardiovascular complications can be reduced.
Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine
Migraine is a debilitating neurological disorder characterized by recurring headache attacks lasting 4-72 hours. Although migraine is common, the pathophysiological causes of this disorder remain unknown. Evidence suggests the importance of the central nervous system (CNS) in the pathology of all migraine variants; however, drug development remains focused on peripheral targets. Migraine therapeutics including triptans, calcitonin generelated peptide (CGRP) antagonists, and monoclonal antibodies against CGRP and its receptor are not thought to cross the blood-brain barrier (BBB). Nonetheless, triptans and CGRP antagonists have been shown experimentally to bind to and exert actions in migraine-relevant regions of the CNS. Some studies have observed increased permeability of the BBB in migraine, which may partially account for the CNS activity of these drugs. Adding to the complexity of the disorder, different migraine variants such as familial hemiplegic migraine (FHM), migraine with aura, and migraine without aura have different underlying pathological mechanisms. In FHM and migraine with aura, cortical spreading depression (CSD) is thought to trigger both the aura phase as well as meningeal primary nociceptor activation in migraine. The cause of CSD in patients experiencing migraine with aura is largely unknown; however studies indicate that sex hormones, corticosteroids, inflammatory mediators such as CGRP, and genetic factors play an important role. Furthermore, CSD has also been correlated with an increase in BBB permeability, strengthening the argument for migraine drug activity in the CNS. It is clear from the mounting evidence, both preclinical and clinical, that CNS mechanisms play an important role in the underlying pathology of migraine. It is therefore vital that future studies continue to investigate these CNS mechanisms in order to create new, more effective treatments to treat and prevent migraine.
In the past few years, knowledge on the resistance to therapy with monoclonal antibodies in colorectal cancer has evidenced the role of mutations in a series of proteins involved in the epidermal growth factor receptor (EGFR) pathway. KRAS mutations can influence the response to therapy, as demonstrated by clinical utilization of cetuximab and panitumumab that are indicated only in KRAS wild-type colorectal cancer. Recently, it has been demonstrated that the mutational status of other proteins like NRAS, BRAF, PI3K or alterations in EGFR and other tyrosine kinase receptors are involved both in primary and secondary resistance to anti-EGFR monoclonal antibodies and could predict the patient response and survival. Many therapeutic strategies have been studied to overcome resistance to these drugs, which include the use of drugs directed against proteins involved in the intracellular signalling pathway of EGFR, such as inhibitors of MEK, BRAF, PI3K/mTOR, or directed against other tyrosine kinase receptors such as MET and HER2. This review will analyse recent strategies utilized to overcome resistance to anti-EGFR monoclonal antibodies in colorectal cancer.
PAMFix is a fixative that was developed to stabilise the platelet biomarker P-selectin on activated platelets. Stabilisation of this biomarker introduced the possibility of performing measurements of platelet function remotelywhere there was no access to special equipment or technical expertise. The idea was to use PAMFix to fix the platelets after stimulating platelets in blood, after which the stabilised samples would be transported to a central laboratory for ana`lysis by flow cytometry. This would obviate the need for special equipment or technical expertise at or near the point at which the blood was collected and processed. Here we demonstrate the stability of samples of blood treated with PAMFix and describe several applications which the use of PAMFix has proved to be particularly beneficial.
An established body of recent literature has demonstrated potent inhibitory effects of the angiotensin converting enzyme-2 (ACE-2)/ANG1-7/ Mas axis on acute lung injury and lung fibrogenesis. One of the mechanisms of this inhibition is the enzymatic action of ACE-2 to degrade its main substrate angiotensin (ANG) II, thereby reducing the injurious and profibrotic activities of this octapeptide. Another, potentially more important mechanism is the production by ACE-2 of the heptapeptide ANG1-7, which inhibits the actions of ANGII through its own receptor Mas, the product of the oncogene of the same name. Very recent efforts to define the molecular and cellular mechanisms of ANG1-7/Mas action have revealed a number of similar, but mechanistically distinct, pathways by which ANG1-7 and Mas act on various lung cell types to inhibit lung injury and fibrosis. In this review we summarize the beneficial actions of the ANG1-7/Mas pathway, specifically on lung cells in non-neoplastic lung injury. We also review the currently known downstream signaling mechanisms of the ANG1-7/Mas pathway in various lung cell types known to be key in acute injury and fibrogenesis.
We investigated the dose-dependent biphasic effects of arsenic disulfide (As2S2) on the differentiation and apoptosis of HL-60 cells. Cellular reactive oxygen species, glutathione, p38 mitogen-activated protein kinase (MAPK), as well as cell differentiation and apoptosis in HL-60 cells were assessed by flow cytometric analysis. The mean percentage of CD11b-positive cells induced by 8 μM As2S2 was more than 3 times higher than that induced by 16 μM As2S2. Eight μM As2S2 did not induce cell apoptosis, while 16 μM As2S2 induced apoptosis and decreased cell viability. Both 8 and 16 μM As2S2 increased cellular reactive oxygen species. Treatment with 16 μM As2S2 decreased the cellular glutathione levels at 1 h and 3 h after the exposure. The mitochondrial membrane potential depletions were observed in both 8 μM As2S2-induced differentiation and 16 μM As2S2induced apoptosis. p38 MAPK inhibition enhanced As2S2-induced differentiation, but had little influence on As2S2-induced apoptosis. A moderate oxidative stress induced by 8 μM As2S2 can promote As2S2induced differentiation, whereas more severe oxidative stress caused by glutathione depletion by 16 μM As2S2 reduced mitochondrial membrane potential, resulting in differentiation attenuation and apoptosis enhancement. p38 MAPK activation resulting from oxidative stress seems to be implicated in negative regulation of cell differentiation, rather than apoptosis, in As2S2-treated HL-60 cells.
