Baseline Narcosis for the Glass-Vial 96-h Growth Inhibition of the Nematode C. elegans and Its Use for Identifying Electrophilic and Pro-Electrophilic Toxicity.

The nematode Caenorhabditis elegans has been widely used as a model organism for assessing chemical toxicity. So far, however, a respective baseline narcosis reference has been lacking to predict narcosis-level toxicity and to identify excess-toxic compounds and associated mechanisms of action. Employing 22 organic narcotics that cover 7.2 units of their log Kow (octanol/water partition coefficient) from -1.20 to 6.03, a baseline narcosis model has been derived for a glass-vial 96-h growth inhibition test with C. elegans, both without and with correction for compound loss through volatilization and sorption. The resultant effective concentrations yielding 50% growth inhibition, EC50, vary by 6.4 log units from 5.04 · 10-1 to 1.90 · 10-7 mol/L (exposure-corrected). Application of the new model is illustrated through sensing the toxicity enhancement (Te) of four Michael-acceptor carbonyls driven by their reactive mode of action. Moreover, narcosis-level predicted vs experimental EC50 of two α,ß-unsaturated alcohols demonstrate the biotransformation capability of C. elegans regarding ADH (alcohol dehydrogenase). The discussion includes narcosis-level and excess-toxicity doses (critical body burdens) as well as chemical activities A50 (at the EC50) as compared to fish, daphnids, ciliates, bacteria, zebrafish embryo, and cell lines. Overall, the presently introduced model for predicting C. elegans baseline narcosis enables generating respective pre-test expectations, enriches experimental results by mechanistic information, and may complement 3Rs (reduce, refine, replace) test batteries through its ADH metabolic capacity.

Frequency and Predictors of Acute Kidney Injury in Patients With Acute Coronary Syndrome in a Tertiary Care Hospital: A Retrospective Study.

Introduction Acute kidney injury (AKI) is a complex condition marked by rapid deterioration of renal function (within hours or days), with clinical symptoms ranging from a minor rise in serum creatinine to anuric renal failure needing renal replacement therapy. AKI is one of the complications of acute coronary syndrome (ACS). This study aims to determine the frequency of AKI among patients with ACS and identify its predictors. Method This study is a retrospective observational study conducted at the Dow University of Health Sciences, a tertiary care hospital located in Karachi, Pakistan. This study was conducted from January 2020 to June 2021. All patients aged 18-75 years admitted with ACS and admitted for more than 48 hours were included in the study. A pre-set questionnaire was used to collect data from the hospital management information system (HMIS). Results The frequency of AKI among patients with ACS was 24.18%. The factors associated with AKI among patients with ACS on multivariable logistic regression included the age of patients (odds ratio (OR) = 1.04, p-value = 0.018), having diabetes mellitus (OR = 2.33, p-value = 0.031), admission Killip ≥ II (OR = 2.12, p-value = 0.041), previous history of myocardial infarction (MI) (OR = 3.64, p-value = 0.001), baseline glomerular filtration rate (GFR) (OR = 0.94, p-value = 0.001), in-hospital ejection fraction (EF) (OR = 0.93, p-value = 0.001), and serum creatinine at admission (OR = 1.02, p-value = 0.001). Conclusion Age, comorbidities including diabetes mellitus and previous history of MI, admission Killip ≥ II, baseline GFR, in-hospital EF, and serum creatinine level at admission are significant independent predictors of AKI in patients with ACS.

Retraction: Frequency and Predictors of Acute Kidney Injury in Patients With Acute Coronary Syndrome in a Tertiary Care Hospital: A Retrospective Study.

[This retracts the article DOI: 10.7759/cureus.21869.].

Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective.

Withania somnifera L. is a multipurpose medicinal plant of family Solanaceae occurring abundantly in sub-tropical regions of the world. The folk healers used the plant to treat several diseases such as fever, cancer, asthma, diabetes, ulcer, hepatitis, eyesores, arthritis, heart problems, and hemorrhoids. The plant is famous for the anti-cancerous activity, low back pain treatment, and muscle strengthening, which may be attributed to the withanolide alkaloids. W. somnifera is also rich in numerous valued secondary metabolites such as steroids, alkaloids, flavonoids, phenolics, saponins, and glycosides. A wide range of preclinical trials such as cardioprotective, anticancer, antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, anti-depressant, and hypoglycemic have been attributed to various parts of the plant. Different parts of the plant have also been evaluated for the clinical trials such as male infertility, obsessive-compulsive disorder, antianxiety, bone and muscle strengthening potential, hypolipidemic, and antidiabetic. This review focuses on folk medicinal uses, phytochemistry, pharmacological, and nutrapharmaceutical potential of the versatile plant.

A comprehensive review of phytochemical profile, bioactives for pharmaceuticals, and pharmacological attributes of Azadirachta indica.

Azadirachta indica L. is a multipurpose medicinal tree of family Meliaceae. It occurs in tropical and semitropical regions of the world. Different parts of this miraculous tree are used to treat pyrexia, headache, ulcer, respiratory disorders, cancer, diabetes, leprosy, malaria, dengue, chicken pox, and dermal complications. The tree is popular for its pharmacological attributes such as hypolipidemic, antifertility, microbicidal, antidiabetic, anti-inflammatory, hepatoprotective, antipyretic, hypoglycemic, insecticidal, nematicidal, antiulcer, antioxidant, neuroprotective, cardioprotective, and antileishmaniasis properties. A. indica is also rich in various phytochemicals for pharmaceuticals such as alkaloids, steroids, flavonoids, terpenoids, fatty acids, and carbohydrates. The fungicidal potential of the tree is due to the presence of azadirachtin and nimbin. Herein, we have compiled a comprehensive review of phytochemical profile, pharmacological attributes, and therapeutic prospective of this multipurpose tree.

Non-compaction of the left ventricle and associated ventricular septal defect.

A case report of a 28-year-old patient, who presented with symptoms and signs of congestive heart failure and had clinical signs of ventricular septal defect as well. On further work-up echocardiogram showed non-compaction of the left ventricle with severe left ventricular systolic dysfunction and a ventricular septal defect. He was treated with standard treatment of heart failure and is doing well.