Hepatic lysosomal enzymes activity and liver morphology after short-time omeprazole administration

The aim of the study was to establish the influence of short-time omeprazole administration on liver function and morphology. Omeprazole was administered intraperitoneally, twice daily, for 3 days to male Wistar rats in two doses: 0.571 mg/kg and 5.71 mg/kg. Control animals were treated with physiological saline. Half of the animals were sacrificed 12 hours after the last injection. The remaining rats were raised for another 6 weeks, without any xenobiotics, and sacrificed on the 47th day of the experiment. The activity of free and bound fractions of hepatic acid phosphatase, beta-galactosidase, beta-N-acetyl-glucosaminidase, cathepsin B, D and L, lipase, and sulphatase were determined spectrophotometrically in homogenates of the liver. The liver sections were examined by light microscopy with hematoxylin-eosin, azan, and periodic acid-Schiff stains. Marginally significant (p < 0.1) differences in activity of free sulphatase fraction, and free and bound fractions of beta-galactosidase were found in animals exposed to the higher dose of omeprazole and sacrificed 12 hours after the last injection. Enzymatic profiles were normalised during the next 6 weeks. Histological evaluation revealed small degenerative and adaptive changes in all examined groups. It could be concluded that observed differences of hepatic lysosomal enzyme activities were the result of accompanied chemical-induced peritonitis as previously reported, and not a direct drug-toxic effect.     

Metastatic potential of human CX-1 colon adenocarcinoma cells is dependent on the expression of sialosyl Le a antigen

Several lines of evidence indicate that sialosyl Le a , tumor-associated carbohydrate antigen present on human colon carcinoma cells, is involved in formation of metastases. To study the role of this carbohydrate structure in development of metastases, we have used the clone of human colon carcinoma CX-1 cells transfected with antisense expression vector containing fragment of cDNA for a1,3/4-fucosyltransferase (FT III), which is involved in synthesis of sialosyl Le a tetrasaccharide. It has been reported previously that, in contrast to the parental cells, the antisense-transfected CX-1.1AS5 cells do not express sialosyl Le a and do not adhere to E-selectin-expressing CHO cells. In the present work we have studied the formation of liver metastases by CX-1.1AS5 cells after their orthotopic or intrasplenic implantation into athymic nu/nu mice. After orthotopic implantation of sialosyl Le a -negative colon carcinoma CX-1.1AS5 cells, the number of mice with liver metas-tases was markedly lower (21% of mice) in comparison with their number after implantation of the parental CX-1.1 cells (86% of mice). However, no differences in ability to form colonies in liver were observed between parental CX-1.1 cells and antisense-transfected CX-1.1AS5 cells after intrasplenic inoculation. The liver metastases were formed in 89% and 84% of mice, respectively. Our data support the thesis on the importance of sialosyl Le a antigen expression in the development of liver metastases by colon cancer cells, and indicate the role of transplantation route and primary tumor localization in formation of metastases.© Kluwer Academic Publishers 1998     

The effect of the intramolecular C–H⋯O interactions on the conformational preferences of bis-arylsulfones – 5-HT6 receptor antagonists and beyond

The development of compounds with enhanced activity and selectivity by a conserved spatial orientation of the pharmacophore elements has a long history in medicinal chemistry. Rigidified compounds are an example of this concept. However, the intramolecular interactions were seldom used as a basis for conformational restraints. Here, we show the weak intramolecular interactions that contribute to the relatively well-conserved geometry of N1-arylsulfonyl indole derivatives. The structure analysis along with quantum mechanics calculations revealed a crucial impact of the sulfonyl group on the compound geometry. The weak intramolecular C–H⋯O interaction stabilizes the mutual "facing" orientation of two aromatic fragments. These findings extend the pharmacological interpretation of the sulfonyl group role from the double hydrogen bond acceptor to the conformational scaffold based on intramolecular forces. This feature has, to date, been omitted in in silico drug discovery. Our results should increase the awareness of researchers to consider the conformational preference when designing new compounds or improving computational methods.

The impact of weak intramolecular C–H⋯O interactions on the conformational stability of bis-arylsulfones is discussed, suggesting different role of sulfonyl group in the ligand – 5HT₆ receptor interaction.     

Numerical and In Vitro Investigation of a Novel Mechanical Circulatory Support Device Installed in the Descending Aorta

Traditional implantation techniques of assist devices from the apex of left ventricle to the ascending or descending aorta are highly invasive and carry substantial complications for end‐stage heart failure patients. This study has shown that the descending aorta can be a promising location to install an implantable mechanical circulatory support with minimally invasive surgery. Herein, the hemodynamic effect of an in‐house prototyped pump implanted in the descending aorta was investigated numerically as well as experimentally. The objective of the experimental study is met by using the in‐house simulator of the cardiovascular loop replicating congestive heart failure conditions. The objective of the numerical study was met by using the modified version of the concentrated lumped parameter model developed by the same team. The results show that the pump placement in the descending aorta can lead to an improvement in pulsatility. The pressure drop, generated at the upstream of the pump, facilitates the cardiac output as a result of after‐load reduction, but at the same time, it induces a slight drop in the carotid as well as the coronary perfusion. The pressure rise, generated at the downstream of the pump, improves the blood perfusion in the renal circulation.     

The quality of systematic reviews/meta‐analyses published in the field of bariatrics: A cross‐sectional systematic survey using AMSTAR 2 and ROBIS

High‐quality systematic reviews (SR) and meta‐analyses (MA) are considered to be reliable sources of information. This study aims to assess the quality of studies published as SR or MA in the field of bariatrics in 2016 and 2017. We identified SR and MA in the field of bariatrics by searching electronic databases (MEDLINE, Embase, and Cochrane Database of Systematic Reviews). Eligible studies were those identified as SR/MA in the title/abstract, which aimed to assess any outcome in patients with morbid obesity undergoing or scheduled to undergo bariatric surgery. Two authors independently reviewed all titles and abstracts, assessed full texts of potentially eligible studies, and assessed the quality of included studies. Any discrepancies were resolved by the third reviewer. We evaluated the quality and risk of bias of each SR/MA using AMSTAR 2 checklist and ROBIS tool, respectively. Seventy‐eight of 4236 references met inclusion criteria and were assessed for their quality/risk of bias. The methodological quality of 99% of all papers was classified as “critically low.” A total of 6% of the studies were at low risk of bias, and 78% were assessed as being at high risk of bias. The methodological quality of studies published in 2016 and 2017 as SR/MA is highly unsatisfactory.     

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

Introduction

CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy.

Material and methods

The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique.

Results

IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher R_V5(6) and R_V5(6) + S_V1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes.

Conclusions

Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.     

A Sensitive Microtitre Plate Enzyme Immunoassay of Oestradiol-17β in the Cow and Mare

Abstract

Microtitre plates were coated with antiserum against oest-radiol-17β-6-(0-carboxymethyl)-oxime bovine serum albumin raised in sheep. The plasma samples (0.2–1.0 ml) were extracted with peroxide-free dlethyl ether prepared daily by treatment with Al₂O₃. The enzyme conjugate was prepared by coupling oestradiol-17β-6-(0-carboxymethyl)-oxime to horse-radish peroxidase. The conjugate was chromatographed on a Sephadex G-25 column. The standard curve ranged from 0.37 to 18.40 fmol/well of oestradiol-17β. The amount of oestradiol-17β causing a 50% reduction of maximum binding was 4.4 fmol/well.

Standards and samples were Incubated overnight at 4°C. The conjugate solution was added followed by further incubation for 2 h at 4°C. Tetramethylbenzidine was used as a chromogen, and the optical density was measured at 450 nm. The patterns of oestradiol-17β during a normal oestrus cycle in the cow and mare are presented.