Sinomenine inhibits microglial activation by Aβ and confers neuroprotection

Abstract Background Neuroinflammation is an important contributor to the development of neurodegenerative diseases, including Alzheimer's disease. Thus, there is a keen interest in identifying compounds, especially from herbal sources, that can inhibit neuroinflammation. Amyloid-β (Aβ) is a major component of the amyloid plaques present in the brains of Alzheimer's disease patients. Here, we examined whether sinomenine, present in a Chinese medicinal plant, prevents oligomeric Aβ-induced microglial activation and confers protection against neurotoxicity. Methods Oligomeric amyloid-β was prepared from Aβ(1-42). Intracellular reactive oxygen species production was determined using the dye 2',7'-dichlorodihydrofluorescin diacetate. Nitric oxide level was assessed using the Griess reagent. Flow cytometry was used to examine the levels of inflammatory molecules. BV2-conditioned medium was used to treat hippocampal cell line (HT22) and primary hippocampal cells in indirect toxicity experiments. Toxicity was assessed using MTT reduction and TUNEL assays. Results We found that sinomenine prevents the oligomeric Aβ-induced increase in levels of reactive oxygen species and nitric oxide in BV2 microglial cells. In addition, sinomenine reduces levels of Aβ-induced inflammatory molecules. Furthermore, sinomenine protects hippocampal HT22 cells as well as primary hippocampal cells from indirect toxicity mediated by Aβ-treated microglial cells, but has no effect on Aβ-induced direct toxicity to HT22 cells. Finally, we found that conditioned medium from Aβ-treated BV2 cells contains increased levels of nitric oxide and inflammatory molecules, but the levels of these molecules are reduced by sinomenine. Conclusions Sinomenine prevents oligomeric Aβ-induced microglial activation, and confers protection against indirect neurotoxicity to hippocampal cells. These results raise the possibility that sinomenine may have therapeutic potential for the treatment of Alzheimer's diseases as well as other diseases that involve neuroinflammation.</p

Vaginal progesterone after tocolytic therapy in threatened preterm labour

Background: Currently preterm labour is one of the most challenging problem faced by both obstetricians and perinatologists, this episode in the course of woman’s pregnancy takes a heavy tool for perinatal mortality which accounts for approximately 50-75%. The incidence of preterm labour is estimated to be 5-10% of all pregnancies.Methods: It was a prospective randomize control trail over a period of 3 year at department of obstetrics and gynecology, tertiary care hospital Pune, Maharashtra, India. Total 100 subjects were randomized into two groups with group one receiving vaginal micronized progesterone and group two control group receiving only tocolytics and steroids. Subsequently authors compared the safety and efficacy of vaginal micronized progesterone versus placebo as a maintenance therapy in preventing preterm labour.Results: This analysis showed that women who randomized to progesterone prophylaxis had a significantly increase in duration of pregnancy. The mean of birthweight in Group A and Group B was 2963±36 gm and 2567±49 gm and respectively which confirmed the positive effects of progesterone on increasing infants’ weights at birth.Conclusions: Authors concluded that progesterone therapy had acceptable efficacy in the prevention of preterm labor in terms of prolongation of delivery and by increasing gestational age at delivery

AYURVEDIC MANAGEMENT OF GUILLAIN-BARRÉ SYNDROME: A CASE STUDY

Guillain-Barré syndrome is a disorder which is caused by the body's immune system attacking its own peripheral nervous system. The syndrome afflicts about one person in 100,000. Either gender can be affected in any age group especially between ages 30 and 50, however risk increases with age. It often follows a minor infection Most of the time, signs of the original infection have disappeared before the symptoms of Guillain-Barré begin. Guillain-Barré syndrome damages parts of nerves. This nerve damage causes tingling, muscle weakness, and paralysis. Guillain-Barré syndrome most often affects the nerve's covering (myelin sheath). Such damage is called demyelination and it causes nerve signals to move more slowly. Damage to other parts of the nerve can cause the nerve to stop working altogether. It is a paralyzing syndrome which can have dire consequences if not managed by an informed medical team. This article will explain how this disorder begins, how it is managed in Ayurveda. It can be compared to Kaphavruta vyana, so approach is to treat Kapha first and then to Vata with Brihmana chikitsa

Assessment of heavy metal contamination in Kali river, Uttar Pradesh, India

The River Kali is an important surface water body in the western Uttar Pradesh (U.P). It is an intermittent river which flows throughout the monsoonal months. The present study aims to assess the heavy metal contamination in the river Kali using pollution index (PI), based on five heavy metals (Fe, Zn, Cd, Pb, and Cr) during pre and post monsoon seasons in the year 2014. The PI evaluated during pre and post monsoon seasons with respect to drinking water quality standards was found as 5.04 and 7.08 respectively, while related to inland water quality standards were found as 4.37 and 3.62, respectively. The results indicate that the river Kali was severely contaminated (PI&gt;3) in both seasons. Therefore, water of Kali River is not fit for drinking as well as for agriculture purposes

Automated Fuel Station with Fake Currency Detection

This paper proposes an automated fuel system using currency detection, which aims at safe and secure fuel delivery, ensuring that the customer gets the equivalent amount of fuel for what he or she is paying, hence successfully eliminating any sorts of malpractices that might occur at a various fuel stations. This system is working on digital image processing and automation technology

Scale-up of cell culture processes using Digital Twins

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Evaluation of prescribing pattern of drugs and compliance to standard treatment guidelines in patients of chronic hepatitis B: a prospective observational study

Background: Hepatitis B is a major global health problem. Chronic hepatitis B is characterized by hepatic inflammation, necrosis and persistence of HbsAg for at least 6 months. Chronic liver disease is more predictably associated with impaired metabolism of drugs than acute liver dysfunction. Prescribing drugs in patients with chronic hepatitis B is challenging because of concerns that the drug may exacerbate the liver disease. There is also the fear that the altered liver state may change metabolism and excretion of the drug. Methods: A cross-sectional prospective study was conducted involving patients diagnosed with chronic hepatitis B at the liver clinic outpatient department (OPD) of AIIMS Bhopal. A total of 102 patients with chronic hepatitis B who met the inclusion criteria were recruited in the study. Results: Out of 102 prescriptions, 492 drugs were prescribed for the 102 patients. Out of 102 patients, 81 patients (81.66%) were on entecavir monotherapy and rest 21 patients (18.34%) were on tenofovir disoproxil fumarate (TDF) monotherapy. Of the 102-prescription issued, 92.15% (94/102) were compliant and 7.85% (8/102) were noncompliant.  Conclusions: Entecavir was the most common antiviral drug prescribed, followed by tenofovir in patients of chronic hepatitis B. Spironolactone plus torasemide combination was the most common fixed dose combination used among study participants. Liver cirrhosis followed by portal hypertension was the most common complication. Majority of prescriptions were compliant with recommendations for pharmacotherapy and safety guidelines in patients of chronic hepatitis B.

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity

Impact of IRS: Four-years of entomological surveillance of the Indian Visceral Leishmaniases elimination programme

BACKGROUND In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. METHODS Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. RESULTS Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. CONCLUSION Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets