[Zwiekszenie czestosci zachorowania na ostre popaciorkowcowe klebuszkowe zapalenie nerek w pierwszej polowie roku 2018 - doswiadczenie jednego osrodka]. / Increased frequency of acute poststreptococcal glomerulonephritis in the first half of 2018 ­ single-center experience.

Acute poststreptococcal glomerulonephritis (APSGN) is a complication of infection with group A beta-hemolytic streptococcus. The disease manifests as microscopic/gross hematuria, arterial hypertension, edema, and acute kidney injury and has most commonly self-limiting course. AIM: The aim of study was the analysis of clinical course of APSGN in period of increased incidence in the first half of 2018. MATERIALS AND METHODS: We analyzed following parameters in children hospitalized due to APSGN in January-June 2018: age, sex, anthropometric parameters, preceding infection, clinical signs, renal function, biochemical and immunological tests (including antristreptolysins (ASO) and complement), urinalysis, renal ultrasonography, and treatment. The incidence of APSGN in years 2007-2018 was analyzed. RESULTS: We found 11 children (6 boys, 5 girls) aged 5.01±2.44 years. The disease was preceded by pharyngitis in 8, skin infection in 1 with latent period 16.40±5.77 days. Clinical symptoms were: gross hematuria in 8, edema in 6, hypertension in 5, renal function impairment 6, and hyperkalemia in 5; all patients had lowered C3 complement factor; ASO was elevated in all patients except for a boy with skin infection. During hospitalization clinical symptoms resolved in all children; significant elevation in GFR (p=0.018) and C3 (p=0.034), and decrease in proteinuria (p=0.039) were observed. Four patients with abnormal ultrasonographic kidney image were characterized by worse kidney function (p=0.018), higher potassium concentration (p=0.052), higher proteinuria (p=0.073) and erythrocyturia (p=0.015) than remaining children. In follow-up (after 142,00±89,20days) all children had normal renal function and blood pressure, 1 patient had proteinuria, and 4 had erythrocyturia. CONCLUSIONS: In most cases APSGN is characterized by rapid resolution of symptoms and good prognosis, but patients require periodic follow-up visits. Abnormal initial ultrasonographic kidney image may be a marker of worse clinical course of APSGN.

The effects of statins on the mevalonic acid pathway in recombinant yeast strains expressing human HMG-CoA reductase.

BACKGROUND: The yeast Saccharomyces cerevisiae can be a useful model for studying cellular mechanisms related to sterol synthesis in humans due to the high similarity of the mevalonate pathway between these organisms. This metabolic pathway plays a key role in multiple cellular processes by synthesizing sterol and nonsterol isoprenoids. Statins are well-known inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the cholesterol synthesis pathway. However, the effects of statins extend beyond their cholesterol-lowering action, since inhibition of HMGR decreases the synthesis of all products downstream in the mevalonate pathway. Using transgenic yeast expressing human HMGR or either yeast HMGR isoenzyme we studied the effects of simvastatin, atorvastatin, fluvastatin and rosuvastatin on the cell metabolism. RESULTS: Statins decreased sterol pools, prominently reducing sterol precursors content while only moderately lowering ergosterol level. Expression of genes encoding enzymes involved in sterol biosynthesis was induced, while genes from nonsterol isoprenoid pathways, such as coenzyme Q and dolichol biosynthesis or protein prenylation, were diversely affected by statin treatment. Statins increased the level of human HMGR protein substantially and only slightly affected the levels of Rer2 and Coq3 proteins involved in non-sterol isoprenoid biosynthesis. CONCLUSION: Statins influence the sterol pool, gene expression and protein levels of enzymes from the sterol and nonsterol isoprenoid biosynthesis branches and this effect depends on the type of statin administered. Our model system is a cheap and convenient tool for characterizing individual statins or screening for novel ones, and could also be helpful in individualized selection of the most efficient HMGR inhibitors leading to the best response and minimizing serious side effects.

Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

BACKGROUND: Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients. METHODS AND RESULTS: Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1(st) day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05) were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase) and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor), IL-10 and IL-6 (interleukin 10 and 6). CONCLUSIONS: In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.

Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study.

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly regarded as well tolerated. However, serious adverse effects have also been reported, especially during high-dose statin therapy. The aim of our study was to investigate the effect of statins on gene expression profiles in human hepatoma HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of 102, 857 and 1091 genes was changed substantially in HepG2 cells treated with simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene ontology analysis showed that many of the genes with changed expression levels were involved in a broad range of metabolic processes. The presented data clearly indicate substantial differences between the tested statins.

Investigating the effects of statins on cellular lipid metabolism using a yeast expression system.

In humans, defects in lipid metabolism are associated with a number of severe diseases such as atherosclerosis, obesity and type II diabetes. Hypercholesterolemia is a primary risk factor for coronary artery disease, the major cause of premature deaths in developed countries. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol synthesis pathway. Since yeast Saccharomyces cerevisiae harbours many counterparts of mammalian enzymes involved in lipid-synthesizing pathways, conclusions drawn from research with this single cell eukaryotic organism can be readily applied to higher eukaryotes. Using a yeast strain with deletions of both HMG1 and HMG2 genes (i.e. completely devoid of HMGR activity) with introduced wild-type or mutant form of human HMGR (hHMGR) gene we investigated the effects of statins on the lipid metabolism of the cell. The relative quantification of mRNA demonstrated a different effect of simvastatin on the expression of the wild-type and mutated hHMGR gene. GC/MS analyses showed a significant decrease of sterols and enhanced conversion of squalene and sterol precursors into ergosterol. This was accompanied by the mobilization of ergosterol precursors localized in lipid particles in the form of steryl esters visualized by confocal microscopy. Changes in the level of ergosterol and its precursors in cells treated with simvastatin depend on the mutation in the hHMGR gene. HPLC/MS analyses indicated a reduced level of phospholipids not connected with the mevalonic acid pathway. We detected two significant phenomena. First, cells treated with simvastatin develop an adaptive response compensating the lower activity of HMGR. This includes enhanced conversion of sterol precursors into ergosterol, mobilization of steryl esters and increased expression of the hHMGR gene. Second, statins cause a substantial drop in the level of glycerophospholipids.