Stigmasterol, a naturally occurring phytoestrogen has been reported to possess many pharmacological activities. The aim of the present study was to screen the effect of stigmasterol against ...ketamine-induced mice model of psychosis.
The behavioural studies included an assessment of locomotor activity, stereotypic behaviours, immobility duration, step down latency and effects on catalepsy. Biochemical estimations involved the estimations of GABA, dopamine, GSH, MDA, TNF-α, total protein content and AChE activity. Histopathological changes and effect on androgenic parameters were also evaluated.
Stigmasterol treated animals showed significant decrease in locomotor activity, stereotypic behaviours, immobility duration and increased step down latency. Biochemical estimations revealed increased GABA, GSH levels and decreased dopamine, MDA, TNF-α levels and AChE activity. These findings were confirmed by histopathological changes in the cortex part of the brain. Further, stigmasterol was not found to cause catalepsy and any adverse effect on the reproductive system.
This study concluded that stigmasterol could ameliorate ketamine-induced behavioral, biochemical and histopathological alterations in mice showing its potential effects in the management of psychotic symptoms.
Limited resources of healthcare system and high use of antidepressants have raised some serious concerns regarding proper surveillance system of prescribed medicines. Not much literature is available ...from Pakistan regarding the potential drug-drug interactions (pDDIs) associated with antidepressants.
The objective of this study was to assess the frequency of pDDIs associated with antidepressants, their severity, significance and their association with patient characteristics.
A prospective, observational study was conducted in two major hospitals of Karachi for the period of three months. Patient profiles, medication charts, and physician notes were thoroughly reviewed to gather all the relevant information. Inclusion and exclusion criteria were set prior to data collection. The collected data was then analysed using Micromedex Drug-REAX System. Descriptive and binomial logistic regression analysis was used to express results.
Of 245 prescriptions reviewed, 141 prescriptions had at least one pDDI (57.5%). A total of 181 pDDIs were identified in prescription containing antidepressant. The ratio of pDDI per prescriptions was 0.78. 42.5% interactions were moderate in severity, 30% of interactions were rapid in onset, and 43% were considered as significant interactions. Polypharmacy (OR=3.41, p< 0.001) and presence of chronic problems (OR=2.14, p=0.002) were significantly associated with the occurrence of pDDIs. Citalopram and diclofenac (11.6%) was commonly prescribed interacting pair in this study.
The findings of this study recorded high frequency of antidepressants associated pDDIs. Our results confirm the significant association of polypharmacy with the occurrence of pDDIs with antidepressants. Future studies are warranted to establish these results by including hospitals in different parts of the country.
Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant.
An ...electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.
Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant risk ratio (RR) = 1.12 (0.88, 1.43),
= 0.36; I
= 0% and 50 mg daridorexant RR = 1.25 (0.88, 1.79),
= 0.22; I
= 28% and serious adverse events with 25 mg RR = 0.86 (0.23, 3.19),
= 0.82, I
= 56% and 50 mg RR = 1.32 (0.29, 6.08),
= 0.72, I
= 52% was comparable to placebo Moderate quality evidence. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.
Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.
The registration number is CRD42022335233.
www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).
Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory ...activity, reduces oxidative stress, and inhibits the activity of Transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA). The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension in a rat model. PAH was induced by a single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index and oxidative stress parameters were performed. Additionally, histopathology of lung and right ventricular of heart tissue, immunohistochemistry, expression of α-SMA, endothelial nitric oxide synthase (eNOS), TGF-β, and RT-PCR, and an in vitro study using human umbilical vein endothelial cells (HUVECs) was also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress, and increase in expression of α-SMA and TGF-β receptor 1 compared with MCT control group rats. In HUVECs, the expression of α-SMA was increased, whereas that of eNOS decreased after TGF-β exposure and was substantially reversed after pretreatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the eNOS/TGF-β/α-SMA signaling pathway.
Arsenic contamination has long been recognized as one of the most harmful environmental pollutants resulting from anthropogenic activity. Apart from being an environmental toxicant or pollutant, this ...culpable heavy metal also has detrimental effects on human health. People throughout the world are exposed to arsenic (As) mostly through polluted drinking water. Acute inorganic arsenic (iAs) poisoning causes nausea, vomiting, stomach discomfort, and severe diarrhea. As on long-term exposure is a potent carcinogen, characterized by IARC (International Agency for Research on Cancer). As levels are high mainly in Gangetic regions due to which the people living around are suffering the consequences. The carcinogenicity of As is well established but the immunotoxicity caused by it is still unknown. Some animal model supports the toxicity of As in the immune system as well, but in humans, mainly suffering from human immunodeficiency virus (HIV), it is not well established. iAs suppresses the immune system by acting on different targets and exacerbating infections. Although animal studies have demonstrated that arsenic trioxide (As
2
O
3
) reduces viral rebound and restores CD4 + count in vivo when coupled with antiretroviral medications, elemental AS may have devastating effects on the immune system of HIV patients, making them more prone to opportunistic infections (OIs). It is well known that in later stages of HIV infection, neurological problems also complicate the conditions such as cognitive impairment and AIDS dementia complex (ADC). Along with immunotoxicity, As has the potential to damage HIV patients’ brains.
This article addresses the
immunotoxicity of arsenic and exacerbations caused by it, along with the neurotoxicity, particularly in HIV patients residing near the Gangetic belt.
Visceral leishmaniasis (VL) is a serious public health concern in the Indian state of Bihar, which has been exacerbated by an increasing HIV/AIDS incidence that has resulted in poor clinical ...outcomes. So far, there has been no investigation into the knowledge, attitude, and practices (KAP) of people who have been subjected to hospital-based supervision for VL or HIV/VL co-infection. This study assessed the KAP toward VL infection among 210 VL-infected patients (126 participants with VL and 84 participants with HIV/VL) using a pretested standard questionnaire. The findings are summarized descriptively and KAP scores are classified dichotomously (good/poor). Multivariable logistic regression and bivariate correlation were used in the analysis. The study showed that both VL-infected and co-infected patients exhibited similar deficits in KAP scores toward VL. The HIV/VL participants who had a personal or family history of VL were more likely to have appropriate awareness of and preventive practices toward VL. The independent predictors of attitude index in HIV/VL participants were education, VL family history, and marital status. There was a weak but significant positive correlation between knowledge and practice (
r
s
= 0.321,
p
<0.001), and attitude and practice (
r
s
= 0.294, p<0.001), while knowledge was strongly correlated with attitude (
r
s
= 0.634, p<0.001). Based on the study findings, it is recommended that treatment programs in Bihar should concentrate on strengthening KAP among VL and HIV/VL co-infected patients to prevent reinfection-related complications. Behavior change communication intervention is ideal for tackling this problem. This proposal entails building a comprehensive public health program in endemic regions.
Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present ...study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.
Introduction Artificial intelligence through machine learning uses algorithms and prior learnings to make predictions. Recently, there has been interest to include more artificial intelligence in ...pharmacovigilance of products already in the market and pharmaceuticals in development.Objective The aim of this study was to identify and describe the uses of artificial intelligence in pharmacovigilance through a systematic literature review.Methods Embase and MEDLINE database searches were conducted for articles published from January 1, 2015 to July 9, 2021 using search terms such as 'pharmacovigilance,' 'patient safety,' 'artificial intelligence,' and 'machine learning' in the title or abstract. Scientific articles that contained information on the use of artificial intelligence in all modalities of patient safety or pharmacovigilance were reviewed and synthesized using a pre-specified data extraction template. Articles with incomplete information and letters to editor, notes, and commentaries were excluded.Results Sixty-six articles were identified for evaluation. Most relevant articles on artificial intelligence focused on machine learning, and it was used in patient safety in the identification of adverse drug events (ADEs) and adverse drug reactions (ADRs) (57.6%), processing safety reports (21.2%), extraction of drug-drug interactions (7.6%), identification of populations at high risk for drug toxicity or guidance for personalized care (7.6%), prediction of side effects (3.0%), simulation of clinical trials (1.5%), and integration of prediction uncertainties into diagnostic classifiers to increase patient safety (1.5%). Artificial intelligence has been used to identify safety signals through automated processes and training with machine learning models; however, the findings may not be generalizable given that there were different types of data included in each source.Conclusion Artificial intelligence allows for the processing and analysis of large amounts of data and can be applied to various disease states. The automation and machine learning models can optimize pharmacovigilance processes and provide a more efficient way to analyze information relevant to safety, although more research is needed to identify if this optimization has an impact on the quality of safety analyses. It is expected that its use will increase in the near future, particularly with its role in the prediction of side effects and ADRs.
Leishmaniasis is a protozoal disease declared as an endemic in areas suffering from severe malnutrition and poverty. The factors associated with poverty like low income, ecological factors, and ...malnutrition cause disruption in immunity and host defense increasing risk of infection. Altered resistance to infection and host susceptibility are associated with low micronutrient levels in undernourished patients. Malnutrition has been recognized as a poor predictive marker for leishmaniasis, in particular the deficiency of trace elements like zinc, iron, and vitamin A, B, C, D which has a prominent function in the regulation of innate and adaptive immunity, cell proliferation, human physiology, etc. Malnourishment can exacerbate host sensitivity and pathophysiologic intensity to infection in variety of ways, whereas infection can enhance underlying poor nutrition or enhance host vulnerability and sandfly's urge to attack specific hosts. The intensity of leishmaniasis can be influenced by body mass and micronutrient availability in the blood. Vitamin D, C, zinc, and iron are proved effective in inhibiting the growth of leishmaniasis in both amastigote or promastigote forms, either directly or by acting as precursor for a pathway which inhibits the parasite growth. This article elucidates a new perception to the crucial role of micronutrients and their probable role in the therapeutic outcomes of leishmaniasis. Since there is requirement of novel drugs to fight drug resistance and relapse of leishmaniasis, this article may pave way to understand the importance of micronutrients and their role in therapeutic outcomes of leishmaniasis.
The prevalence of long-term (chronic) non-communicable diseases (NCDs) is increasing globally due to an ageing global population, urbanization, changes in lifestyles, and inequitable access to ...healthcare. Although previously more common in high- and upper-middle-income countries, lower-middle-income countries (LMICs) are more affected, with NCDs in LMICs currently accounting for 85– 90% of premature deaths among 30– 69 years old. NCDs have both high morbidity and mortality and high treatment costs, not only for the diseases themselves but also for their complications. Primary health care (PHC) services are a vital component in the prevention and control of long-term NCDs, particularly in LMICs, where the health infrastructure and hospital services may be under strain. Drawing from published studies, this review analyses how PHC services can be utilized and strengthened to help prevent and control long-term NCDs in LMICs. The review finds that a PHC service approach, which deals with health in a comprehensive way, including the promotion, prevention, and control of diseases, can be useful in both high and low resource settings. Further, a PHC based approach also provides opportunities for communities to better access appropriate healthcare, which ensures more significant equity, efficiency, effectiveness, safety, and timeliness, empowers service users, and helps healthcare providers to achieve better health outcomes at lower costs.
PDF
