Istodobno spektrofotometrijsko određivanje losartan kalija, amlodipin besilata i hidroklorotiazida u farmaceutskim pripravcima kemometrijskom metodom

In the present work, four different spectrophotometric methods for simultaneous estimation of losartan potassium, amlodipine besilate and hydrochlorothiazide in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, classical least squares (CLS), multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix, with measurements in the range of 230.5350.4 nm (∆λ = 0.1 nm) in their zero order spectra. The linearity range was found to be 840, 15 and 315 μg ml1 for losartan potassium, amlodipine besilate and hydrochlorothiazide, respectively. The validity of the proposed methods was successfully assessed for analyses of drugs in the various prepared physical mixtures and in tablet formulations.U radu su opisane četiri spektrofotometrijske metode za istodobno određivanje losartan kalija, amlodipin besilata i hidroklorotiazida u sirovinama i farmaceutskim pripravcima. Podaci koji su se preklapali kvantitativno su razlučeni kemometrijskim metodama, klasičnom metodom najmanjih kvadrata (CLS), multiplom linearnom regresijom (MLR), regresijom glavnih komponenata (PCR) te metodom parcijalnih najmanjih kvadrata (PLS). Kalibracije su provedene koristeći podatke o ovisnosti apsorpcije o koncentracijama, mjereći spektre nultog reda u rasponu 230,5350,4 nm (∆λ = 0,1 nm). Linearnost za losartan kalij bila je 840, za amlodipin besilat 15, a za hidroklorotiazid 315 μg ml1. Valjanost predloženih metoda uspješno je potvrđena analizom navedenih lijekova u različitim pripremljenim smjesama i tabletama

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

Retracted: Spontaneous rectus sheath haematoma associated with rivaroxaban treatment

PMID = 2538190

Effect of Lemon Verbena Polyphenol on Glycerol Channel Aquaporin 7 Expression in 3T3-L1 Adipocytes

Objective: Polyphenols are of great interest in obesity prevention approaches. The aquaglyceroporin 7 (AQP7) channel is involved in the transport of glycerol across cell membranes in adipose tissue. This study aimed to explore how lemon verbena (LV) polyphenols affect the expression of the glycerol channels AQP7 and perilipin 1 (PLIN1) in 3T3-L1 hypertrophic adipocytes. Materials and Methods: Hypertrophic adipocyte cells (H) were treated with LV at two different doses of 200 µg/mL (H-LV200) and 400 µg/mL (H-LV400). In addition, 0.1 µM β3-AR agonist (CL316243) and 0.1 µM β3-AR antagonist (L7483337) were applied to the cells at both doses. AQP7 and PLIN1 gene expressions were determined by real time-polymerase chain reaction (RT-PCR), and glycerol levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Hypertrophic adipocytes showed increased AQP7 and PLIN1 gene expression and glycerol content compared with the control group. H-LV200 and CL316243 treatment together increased AQP7 gene expression, whereas H-LV400 and L7483337 treatment together decreased AQP7 gene expression. Conclusion: The data indicated that both doses of LV inhibited glycerol production by suppressing AQP7 and PLIN1 gene expression. Approaches to regulate AQP7 gene expression in adipose tissue using plant-derived polyphonic compounds are considered a healthy and innovative approach to combat and manage metabolic diseases, including obesity. © 2024, Istanbul University Press. All rights reserved.Trakya Üniversitesi, (TUBAP 2021-11

Investigating the addition of enzymes in gluten-free flours - The effect on pasting and textural properties

A wide range of enzymes (fungal amylase, esterase, hemicellulase, glucose oxidase and transglutaminase) were added to gluten-free flours (buckwheat, corn and rice) at different concentrations (0, 1, 3, 5, 10 g/100 kg flour) to investigate the effects on pasting properties of flour and texture profiles of the flour gels. Concerning the pasting properties, fungal amylase enzyme consistently affected the flour properties. Breakdown of complex starch molecules into simpler sugars due to the enzyme activity decreased the overall viscosity parameters (at least trough viscosity by 50%, breakdown viscosity by 80%, final viscosity by 60% and setback viscosity by 67%) during the application of heating, shearing and cooling cycle. Increasing enzyme concentration decreased these values further due to increase in the rate of hydrolysis. Texture profiles of the flour gels showed good relation with pasting properties. Decreasing viscosity of gluten-free gels by enzymes caused reduction in the firmness of the gels. The hardest gel was found as corn flour at the highest amylase enzyme concentration (10 g/100 kg flour). However, the highest springiness, resilience, cohesiveness and adhesiveness value was observed for buckwheat starch gel. © 2016