Does berberine impact anthropometric, hepatic, and metabolic parameters in patients with metabolic dysfunction-associated fatty liver disease? Randomized, double-blind placebo-controlled trial.

Globally, the metabolic dysfunction-associated fatty liver disease (MAFLD) holds the position as the most widespread chronic liver condition. Berberine (BBR) shows promise as a natural compound for managing obesity, hepatic steatosis, and metabolic disorders. The study aimed to investigate the effectiveness of BBR in addressing factors linked to MAFLD. This is a randomized, double-blind, and placebo-controlled clinical trial. Seventy individuals with MAFLD were enrolled in this study and randomly assigned in a 1:1 ratio to two groups. BBR (1500 mg/day) or placebo was administrated orally for 12 weeks. Selected anthropometric, hepatic, and metabolic parameters were assessed. After a 12-week intervention, the BBR group demonstrated a statistically significant decrease in alanine transaminase (ALT) p=0.0105, and de Ritis ratio p=0.0011 compared to the control group. In both groups we observed a decrease in trunk fat (kg) - BBR group p=0.0185, and placebo group p=0.0323. After three months, a significant divergence between the BBR and placebo groups was evident in the alteration of Δ total cholesterol (TC) p=0.0009, favoring the BBR group. Nevertheless, there were no significant differences detected in other lipid and glucose parameters. In the BBR group, we found significant correlations between changes and amelioration of certain variables: Δ body mass index (BMI) correlated with ΔALT (r=0.47; p=0.0089) and D aspartate aminotransferase (AST) (r=0.47; p=0.0081) levels; Δ trunk fat with Δ fatty liver index (FLI) (r=0.55; p=0.0337), Δ homeostasis model assessment for insulin resistant index (HOMA-IR) (r=0.37; p=0.0020), and AST (r=0.42; p=0.0202); D the de Ritis ratio correlated with Δ fibrosis-4 index (FIB-4) levels (r=0.59; p=0.0011); and ΔFLI correlated with ΔHOMA-IR (r=0.37; p=0.0409) and Δ visceral adiposity index (VAI) (r=0.54; p=0.0019), while no significant differences were observed in the Placebo group. The results show that BBR appears to be a bioactive compound that positively impacts MAFLD, however, additional research with extended intervention durations is required to fully assess its efficacy and potential clinical use.

Analysis of immunohistochemical expression of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in gallbladder mucosa: comparative study in acute and chronic calculous cholecystitis.

BACKGROUND: Several studies have shown increased serum levels of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in patients with cholelithiasis. The local expression of the proteins involved in pathogenesis of the disease is poorly recognised. MATERIALS AND METHODS: The authors examined immunohistochemically (IHC) the expression status of IL-1α, IL-6, and TNF-α in gallbladder mucosa of the patients with cholelithiasis as related to acute (ACC) and chronic (CCC) types of cholecystitis. Proinflammatory cytokines were quantitatively evaluated in gallbladder mucosa (epithelium and lamina propria) in ACC (n = 16) and CCC (n = 55) groups using modern spatial visualisation technique. RESULTS: Quantitative analysis of IHC signals showed no significant differences in IL-1α and IL-6, and immunoexpression in patients with ACC and CCC. A significantly greater IHC expression of TNF-α was detected in CCC as compared with ACC group. In either of the patient groups immunoexpression of IL-1α and of TNF-α was significantly higher than that of IL-6. Immunoexpression of TNF-α was significantly higher than that of IL-1α only in CCC group. A positive correlation was disclosed between IHC expression of IL-1α and body mass index in CCC group. IHC expression of TNF-α correlated positively with expression of CD68 molecule (histiocytic marker), number of leukocytes in blood and higher grading of gallbladder wall in ACC group. CONCLUSIONS: A more pronounced IHC expression of TNF-α and IL-1α than IL-6 in both types of cholecystitis may suggest the role of these cytokines in pathogenesis of cholelithiasis. IHC expression of TNF- α shows better correlation with clinical/laboratory data in acute cholecystitis, and its quantitative prevalence over the remaining cytokines points to the role of the TNF-α in maintenance of inflammation in the course of cholelithiasis.

Expression of phenotypic markers of mast cells, macrophages and dendritic cells in gallbladder mucosa with calculous cholecystitis.

The study aimed at quantitative analysis of expression involving markers of mast cells (tryptase), monocytes/macrophages (CD68 molecule) and dendritic cells (S100 protein) in gallbladder mucosa with acute and chronic calculous cholecystitis. Routinely prepared tissue material from the patients with acute (ACC) (n = 16) and chronic calculous cholecystitis (CCC) (n = 55) was evaluated. Three cellular markers were localized by immunocytochemistry. Their expression was quantified using spatial visualization technique. The expression of tryptase was similar in acute and chronic cholecystitis. CD68 expression in ACC was significantly higher than in the CCC group. Expression of S100 protein was significantly higher in CCC as compared to the ACC group. No significant correlations were disclosed between expression of studied markers and grading in the gallbladder wall. A weak negative correlation was noted between expression of CD68 and number of gallstones in the CCC group. The spatial visualization technique allowed for a credible quantitative evaluation of expression involving markers of mast cells (MCs), monocytes/macrophages (Mo/Ma) and dendritic cells (DCs) in gallbladder mucosa with ACC and CCC. For the first time mucosal expression of S100 protein-positive DCs was evaluated in calculous cholecystitis. The results point to distinct functions of studied cell types in the non-specific immune response in calculous cholecystitis.

[Dual-photon bone densitometry in dialyzed patients]. / Dvoufotonová kostní denzitometrie u dialyzovaných nemocných.

In non-invasive diagnosis of renal osteodystrophy the levels of bone minerals and the extent of bone turnover are evaluated. The contents of bone minerals are assessed quantitatively by different modalities of bone densitometry, among which the most accurate one is double-energy bone densitometry. So far no standard examination method was defined nor the most suitable portion of the skeleton for densitometric examination. In order to find such an area and also to assess the prevalence of bone demineralization, its severity and regional differences the authors made a cross-sectional study of bone density in dialyzed patients. The group comprised 45 patients, 24 men and 21 women subjected to regular dialyzation treatment for 20-24 months. In a lambda whole body bone densitometry was performed with evaluation of regional densities of the trunk, upper and lower extremities. At the same time the state of bone turnover was assessed arbitrarily using values of serum concentrations of intact parathormone; parathormone concentrations below 50 pg/ml were considered low, above 200 pg/ml high and concentrations within the mentioned range as the normal bone turnover. In the group of patients 62% had a high, 22% a normal and 16% a low bone turnover. The study provided evidence of a significant reduction of bone density (Z score <-1) in 58% of patients. In 92% of patients demineralization affected most and first the extremities. In 69% it affected the lower extremities and in 23% the upper ones. 8% of the patients had the most severe affections in the area of the trunk. This order of affliction was not influenced by bone turnover, sex and in women by age. The diaphysis of long bones seems to be a representative examination area of the skeleton for densitometric measurements in patients with regular dialyzation treatment.

Single photon bone densitometry in hemodialysis patients.

Renal osteodystrophy is a common finding in patients with renal insufficiency. The maximum of its intensity is found in hemodialysis patients. Bone densitometry is so far the best method for non-invasive assessment of the extent of the illness. Some densitometric studies in hemodialysis patients have already been published but their results differ in prevalence and intensity of renal osteodystrophy. They also demonstrated a slight relationship between intensity of renal osteodystrophy and duration of the dialysis treatment. Opinions vary on the relationship between bone mineral density and markers of bone turnover. This cross-sectional study found high prevalence of renal osteodystrophy (Z-score below -1 in 57% of patients) as well as high a number of severely damaged patients (T-score below -2.5 in 40% of patients). It also showed some correlation between bone demineralisation and the duration of dialysis. None from evaluated markers of bone turnover correlated with bone mineral density.