Factor Xa inhibitors versus warfarin in patients with non-valvular atrial fibrillation and diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Background: Patients with non-valvular atrial fibrillation with diabetes face increased stroke and cardiovascular risks. This study compares factor Xa inhibitors and warfarin using data from randomized controlled trials (RCTs). Methods: MEDLINE, Embase, and Cochrane CENTRAL databases were searched for RCTs comparing the risk of efficacy and safety of any factor Xa inhibitors with dose-adjusted warfarin by diabetes status. Incidence of stroke/systemic embolism, major bleeding, intracranial hemorrhage, ischemic stroke, all-cause mortality, risk of hemorrhagic stroke, and myocardial infarction were among the outcomes of interest. A generic inverse-weighted random-effects model was used to calculate hazard ratios (HRs) with 95 percent confidence intervals (CIs). Results: After applying exclusion criteria, four RCTs containing 19 818 patients were included in the analysis. Compared with warfarin, meta-analysis showed statistically significant reduction in incidence of stroke/systemic embolism (HR 0.80 [95% CI 0.69-0.92]; P=0.002), intracranial hemorrhage (HR 0.49 [95% CI 0.37-0.65]; P<0.001), and risk of hemorrhagic stroke (HR 0.37 [95% CI 0.20-0.66]; P=0.001) in patients on factor Xa inhibitors. However, there was no discernible difference between two treatment arms in incidence of major bleeding (HR 0.93 [95% CI 0.84-1.04]; P=0.19), ischemic stroke (risk ratio (RR) 0.90 [95% CI 0.73-1.12; P=0.34), myocardial infarction (RR 0.88 [95% CI 0.67-1.15]; P=0.35), and all-cause mortality (RR 0.89 [95% CI 0.79-1.01]; P=0.06). Conclusion: Factor Xa inhibitors show a favorable balance between efficacy and safety compared with warfarin, which is consistent across a wide range of patients with atrial fibrillation known to be at high risk for both ischemic and bleeding events.

Efficacy of ablation therapy on clinical outcomes in patients with atrial fibrillation: a systematic review and meta-analysis.

Background: Optimal treatment regimen for patients with atrial fibrillation (AF) remains unclear. Therefore, the authors sought to compare the outcomes of ablation therapy versus pharmacological regimens in patients with AF. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials and observational studies comparing clinical outcomes between of ablation and pharmacological therapy in patients with AF. Stroke, all-cause mortality, cardiovascular mortality, cardiovascular hospitalization, heart failure (HF), and bleeding were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 % CIs. Results: The analysis included ~200 000 patients from 4 randomized controlled trials and 7 observational studies. Meta-analysis showed statistically significant reduction in stroke among patients on ablation therapy [hazard ratio (HR) 0.51, 95% CI (0.43, 0.60), P<0.00001, I2=10%], all-cause mortality [HR 0.64, 95% CI (0.45, 0.93), P=0.02, I2=58%], cardiovascular mortality [HR 0.35, 95% CI (0.25, 0.50), P<0.0001, I2=0%], and HF [HR 0.40, 95% CI (0.31, 0.53), P<0.00001, I2=30%]. However, no significant difference was revealed in the risk of cardiovascular hospitalization [HR 1.04, 95% CI (0.88, 1.23), P=0.66, I2=89%] and bleeding [HR 1.11, 95% CI (0.97, 1.27), P=0.13, I2=0%]. Conclusion: Ablation significantly reduces the risk of stroke, cardiovascular mortality, all-cause mortality, and HF in AF patients, compared with medical therapy alone, supporting its use in clinical practice.

Efficacy of hypertonic saline versus isotonic saline among children with cystic fibrosis: A systematic review and meta-analysis.

Background: Inhaled hypertonic saline (HS) reduces pulmonary exacerbations in patients with cystic fibrosis (CF) aged 6 or more years. However, the effectiveness of HS in improving clinical outcomes in younger children aged 6 or less years is not established. This study examines the efficacy of HS in younger CF patients. Methods: Searches were conducted across three databases (Medline, Cochrane Central and EMBASE) from inception through July 2022. Randomized controlled trials assessing the impact of HS in younger CF patients were included. Trials involving only patients greater than 6 years or control group other than isotonic saline (IS) were excluded. Outcomes measured included lung clearance index (LCI), cystic fibrosis questionnaire (CFQ-R) score, spirometry measures, oxygen saturation, respiratory rate, height and weight. Outcomes were reported as mean differences (MDs) with 95% confidence intervals. Results: Seven studies (n = 390 patients) were included in this review. HS significantly reduced the LCI (MD: -0.67; 95%CI, -1.05 to 0.29, P = 0.0006) compared to IS. In addition, HS was associated with significant improvements in height (MD: 2.23; 95%CI, -0.00 to 4.46, P = 0.05) and CFQ-R (MD: 4.30; 95%CI, 0.65-7.95, P = 0.02), but not in oxygen saturation (MD: -0.15; 95%CI, -0.54 to 0.25, P = 0.47), respiratory rate (MD: -0.21; 95%CI, -2.19 to 1.77, P = 0.83) or weight (MD: 0.70; 95%CI, -0.47 to 1.87, P = 0.24). Furthermore, HS did not significantly improve spirometry measures, including FEV1 (MD: -0.11; 95%CI, -0.21 to 0.43, P = 0.51) and forced vital capacity (MD: 0.27; 95%CI, -0.49 to 1.04, P = 0.48), but significantly improved FEF25-75 (MD: 0.12; 95% CI, 0.05-0.20; P = 0.002). Discussion: Treatment with HS in younger children with CF improves lung clearance, symptoms and quality of life. FEF25-75 may prove a more sensitive measure for assessing intervention related improvements in pediatric CF trials. Conclusion: The findings support HS as a therapeutic method in CF-affected children.

Effect of Statin Therapy on Mortality and Recurrence of Intracerebral Hemorrhage in Patients With Spontaneous Intracerebral Hemorrhage.

Statins can play an essential role in the tertiary and primary prevention of cardiovascular events by reduction of cholesterol in a stroke patient. This meta-analysis aims to assess statin therapy's effect on mortality and recurrence of Intracranial Hemorrhage (ICH) in patients with spontaneous ICH. The current meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was performed using PubMed, EMBASE, and Cochrane Library to identify studies assessing the use of statins in patients with ICH. The primary outcome assessed in the current meta-analysis was a hemorrhagic stroke. The secondary outcomes included cardiac-related events and all-cause mortality. A total of 9 studies were included in the current meta-analysis enrolling 49027 patients, with 8094 patients on statin therapy and 40933 patients in the control group. The risk of recurrent ICH was significantly lower in patients receiving stains (RR: 0.81, 95% CI: 0.67-0.99, p-value: 0.02) compared to placebo. However, no significant differences were observed regarding all-cause mortality (RR: 0.80, 95% CI: 0.53-1.20, p-value: 0.27) and cardiovascular events (RR: 1.24, 95% CI: 0.88-1.74). In ICH patients, statins can reduce the risk of recurrent ICH in patients with a history of ICH. However, statins had no significant effect on all-cause mortality and cardiovascular events.

Beta-Blocker-Induced Erythrodermic Psoriasis: A Case Report.

Beta-blockers are well-known for their wide range of therapeutic applications, particularly in patients with cardiac diseases. Physicians worldwide are aware of their potential side effects, including hypoglycemia, dizziness, slow heart rate, fatigue, and heart block. We report a case of erythrodermic psoriasis caused by beta-blockers in a 61-year-old woman with no prior history of the skin condition. The diagnosis was made based on the characteristic histopathological picture and a Naranjo score of 6. She was administered 15 mg of methotrexate weekly and received supportive care. She recovered completely within two months and exhibited no recurrence of symptoms.

Synthesis and Investigation of the Analgesic Potential of Enantiomerically Pure Schiff Bases: A Mechanistic Approach.

Schiff bases are a class of organic compounds with azomethine moiety, exhibiting a wide range of biological potentials. In this research, six chiral Schiff bases, three 'S' series (H1−H3) and three 'R' series (H4−H6), were synthesized. The reaction was neat, which means without a solvent, and occurred at room temperature with a high product yield. The synthesized compounds were evaluated for analgesic potential in vivo at doses of 12.5 and 25 mg/kg using acetic-acid-induced writhing assay, formalin test, tail immersion and hot plate models, followed by investigating the possible involvement of opioid receptors. The compounds H2 and H3 significantly (*** p < 0.001) reduced the writhing frequency, and H3 and H5 significantly (*** p < 0.001) reduced pain in both phases of the formalin test. The compounds H2 and H5 significantly (*** p < 0.001) increased latency at 90 min in tail immersion, while H2 significantly (*** p < 0.001) increased latency at 90 min in the hot plate test. The 'S' series Schiff bases, H1−H3, were found more potent than the 'R' series compounds, H4−H6. The possible involvement of opioid receptors was also surveyed utilizing naloxone in tail immersion and hot plate models, investigating the involvement of opioid receptors. The synthesized compounds could be used as alternative analgesic agents subjected to further evaluation in other animal models to confirm the observed biological potential.

Synthesis, Bioactivity Assessment, and Molecular Docking of Non-sulfonamide Benzimidazole-Derived N-Acylhydrazone Scaffolds as Carbonic Anhydrase-II Inhibitors.

This research reports the synthesis of new benzimidazole-derived N-acylhydrazones (NAH), their characterization using various spectroscopic methods, and in vitro evaluation as potent carbonic anhydrase-II inhibitors. Among the target compounds (9-29), few showed higher inhibition than the standard acetazolamide (IC50: 18.6 ± 0.43 µM), for example, compound 9 (IC50: 13.3 ± 1.25 µM), 10 (IC50: 17.2 ± 1.24 µM), 12 (IC50: 14.6 ± 0.62 µM), and 15 (IC50: 14.5 ± 1.05 µM). Molecular docking was performed on the most active compounds, which revealed their binding interactions with the active site of the enzyme, thus supporting the experimental findings.

Extraction optimization, Total Phenolic-Flavonoids content, HPLC-DAD finger printing, antimicrobial, antioxidant and cytotoxic potentials of Chinese folklore Ephedra intermedia Schrenk & C. A. Mey

Abstract Plants from genus Ephedra are commonly used by the Chinese people as folk medicine for treatment of various diseases. The current study was designed to explore the ethno-pharmacological based pharmacological potentials of Ephedra intermedia Schrenk & C.A. Mey. (E. intermedia). Plant aerial parts were extracted using ten solvent systems with increasing order of polarity. Samples were analyzed for total phenolic and flavonoid contents, HPLC-DAD analysis, antibacterial, antifungal, HepG2 cell line cytotoxicity, hemolysis and antioxidant potentials following standard procedures. Highest percent extract recovery was observed in Eth+WT (25.55 % w/w) solvent system. Flavonoid and phenolic contents were higher in chloroform and Met+WT fractions respectively. Considerable antibacterial activity was shown by Eth+Met extract against B. subtilis and K. pneumonia (MIC of 11.1μg/mL for each). Eth extract exhibited high antifungal activity against A. fumigates (15±0.31 mm DIZ). Met+WT extract showed significant cytotoxicity against HepG2 cell lines with IC50 of 13.51+0.69 μg/mL. Substantial free radical scavenging activity (74.9%) was observed for Met+Eth extract. In the current study, several solvent systems were used for more effective extraction of fractions and can be useful in the isolation of phytochemicals. Various fractions exhibited considerable antimicrobial, antioxidant and cytotoxic potentials. Biological potentials of E. intermedia signify its potential uses in microbial, cancer and degenerative disorders and thus warrant further detailed studies.

A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L.

The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.

Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches.

Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature of Eryngium caeruleum, we have evaluated its antidiabetic and antioxidant potentials. Both in-vitro and in-vivo assays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract of E. caeruleum (Ec.Cr) and its sub-fractions [i.e., n-hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC50 of 437 µg/ml in comparison to the standard acarbose (IC50 25 µg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC50 values recorded for Ec.Chf were 112, 109, and 150 µg/ml against DPPH, ABTS, and H2O2 respectively. Based on the in-vitro potential of Ec.Chf, this was subjected to the in-vivo model experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 µg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude that Eryngium caeruleum is a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction of Eryngium caeruleum into active sites of the homology model of α-glucosidase.

Isolation, pharmacological evaluation and molecular docking studies of bioactive compounds from Grewia optiva.

BACKGROUND: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough. METHODS: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3',6',8'-trihydroxyl-4H chromen-4'-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman's assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays. RESULTS: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23±1.11, 82.72±2.20 and 82.11±2.11, 82.23±1.21, respectively, at 1000 µg/mL) with IC50 of 76, 90, 78 and 92 µg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41±1.20 and 86.13±2.31) with IC50 of 64 and 65 µg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme. CONCLUSION: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.

Bio-guided profiling and HPLC-DAD finger printing of Atriplex lasiantha Boiss.

BACKGROUND: Plants represent an intricate and innovative source for the discovery of novel therapeutic remedies for the management of various ailments. The current study has been aimed to validate the therapeutic potential of ethnomedicinally significant plant Atriplex lasiantha Boiss. METHODS: The polarity based extraction process was carried out using fourteen solvents to figure out best extraction solvent and bioactive fractions. Total phenolic-flavonoids contents were quantified colorimetrically and polyphenolics were measured using HPLC-DAD analysis. Moreover, the test samples were tested against several diseases targets following various assays including free radicals scavenging, antibacterial, antifungal, cytotoxic and antileishmanial assay. RESULTS: Among the solvent fractions, maximum yield was obtained with methanol-water extract i.e., 11 ± 0.49%. Maximum quantity of gallic acid equivalent phenolic content and quercetin equivalent flavonoid content were quantified in methanol-ethyl acetate extract of A. lasiantha. Significant quantity of rutin i.e., 0.3 µg/mg was quantified by HPLC analysis. The methanol-ethyl acetate extract of A. lasiantha exhibited maximum total antioxidant and total reducing power with 64.8 ± 1.16 AAE/mg extract respectively, while showing 59.8 ± 1.07% free radical scavenging potential. A significant antibacterial potential was exhibited by acetone-distilled water extract of A. lasiantha with 11 ± 0.65 mm zone of inhibition against B. subtilis. Considerable antifungal activity was exhibited by ethyl acetate-n-hexane extract of aerial part of A. lasiantha with 14 ± 1.94 mm zone of inhibition against A. fumigatus. Highest percentage of α-amylase inhibition (41.8 ± 1.09%) was observed in ethyl acetate-n-hexane extract. Methanol-acetone extract of A. lasiantha demonstrated significant inhibition of hyphae formation with 11 ± 0.49 mm bald zone of inhibition. Significant in-vitro cytotoxicity against Hep G2 cell line has been exhibited by methanol-chloroforms extract of A. lasiantha. CONCLUSION: The current study reveals the prospective potential of Atriplex lasiantha Boiss. for the discovery of biologically active compounds through bioassay guided isolation against various diseases.

Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium Stocksianum bioss collected from the North West of Pakistan.

BACKGROUND: Medicinal plants are used for the treatment of different diseases in almost all cultures. Teucrium species grow wildly at different geographical locations around the world. Teucrium stocksianum is used in folk medicine for the treatment of diarrhea, cough, jaundice and abdominal pain. Scientific study on Teucrium stocksianum shows that it possesses anthelmintic, cytotoxic and antispasmodic activity. The aim of our present study is to identify the chemical composition and antinociceptive potential of the essential oil extracted from Teucrium stocksianum bioss. METHOD: Essential oil (EO) from the aerial parts of Teucrium stocksianum were extracted by hydrodistillation process. The qualitative and quantitative composition of essential oil was determined with Gas chromatography/Mass spectrometer. Antinociceptive activity was determined by acetic acid induced writhing method. Percent inhibition of writhes of the test concentration was determined by comparing it with that of control. Tween-80 emulsion 2.5% (5 ml/kg b.w) was used as a control while Diclofenic sodium 50 mg/kg (b.w) was used as a standard drug. RESULTS: The chromatogram of the essential oil of Teucrium stocksianum shows differences both qualitatively and quantatively from essential oil composition reported in other countries. Hydrodistillation of Teucrium stocksianum yielded 0.4% (v/w), pale yellowish oil on dry basis. A total of 26 chemicals were identified by GC-MS accounting for 90.28% of the oil. The major components of essential oil were δ-cadinene (12.92%), α-pinene (10.3%), myrcene (8.64%), ß-caryophyllene (8.23%), germacrene D (5.18%) and limonene (2.36%). Essential oil of Teucrium stocksianum has shown outstanding antinociceptive activity. It has been observed that increase in percent writhe inhibition (PWI) occurred from 20-80 mg/kg (b.w) and maximum writhe inhibition has been noted at a concentration of 80 mg/kg (b.w), but PWI decreased at 160 mg/kg, which may be due to some toxic effect of higher dose. ED50 value for Teucrium stocksianum was calculated as 31.5 ± 1.72415 mg/kg (b.w). CONCLUSION: Our results indicate that there is a lot of variation in the composition of essential oil of Teucrium stocksianum boiss, which may be due to different climatic and experimental conditions. Secondly, the essential oil possesses strong antinociceptive activity and could be used in analgesic preparations especially for topical use.