1a_Caveolin-1 (CAV-1) is the main structural component of caveolae, acting as a modulator of signal transduction. CAV-1 might be involved in the pathophysiology of microvascular complications in Type 1 diabetes (DM). We sought to determine whether fractionation on sucrose gradient (SF), a method routinely utilized for isolation of caveolar fractions in homogenous cell lines, is applicable for CAV-1-related studies in tissues with multiple cell types, such as the normal rat kidney cortex (C). Using this method, we also determined whether streptozotocin- induced DM in rats (4-week duration) leads to changes in renal subcellular targeting of CAV-1, and evaluated the effects of tight metabolic control (insulin, 12 IU /day) and angiotensin receptor blocker, losartan (4 weeks, 20 mg/kg/day). Immunoblotting of individual fractions obtained from C revealed CAV-1 expression in fractions 4-6 that corresponded to light scattering band that typically forms after separating cellular fractions on SF. These fractions were considered to be caveolar fractions. In C, CAV-1 was also detectable in fracti ons 8-10. These and all other fractions except caveolar fractions were considered to be non-caveolar fractions. A ratio of caveolar/non-caveolar expression of CAV-1 (CNCR) was computed for each renal cortex allowing comparisons of CAV-1 subcellular distribution in C and DM rats, and effects of treatments., 2a_Using this approach, DM was characterized by marked increases in CNCR as compared to C (5.54±1.56 vs. 2.65±1.33, p<0. 05) that were reduced by treatment with insulin (0.78±0. 24, p<0.01 vs. DM) or losartan (0.84±0.06, p<0.01 vs. DM). In summary, analysis of CAV-1 following the SF of renal cortex detected similar distribution of the protein as in homogenous cell lines, DM-induced changes in CAV-1 targeting, and the effects of pharmacological treatments. This suggests applicability of SF in studies focusing on CAV-1 targeting in organs with various cell lines in vivo., H. Demová, R. Komers., and Obsahuje seznam literatury
Vliv natriuretických peptidů na kardiovaskulární a renální systém představuje potenciální možnosti využít tyto působky v léčbě hypertenze a srdečního selhání, i když současné výsledky klinických studií nejsou povzbudivé. Syntetický B-natriuretický peptid sice prokázal krátkodobé hemodynamické zlepšení pacientů, nicméně z pohledu renálních funkcí a dlouhodobé prognózy pacientů byl účinek sporný. Naopak novou nadějí je ularitid a duální inhibitor neprilyzinu a ARB: LCZ 696, u nejž probíhají klinické studie a předchozí data z pilotních studií se jeví slibná., The effect of natriuretic peptides on cardiovascular and renal system offers a potential benefit in therapy of hypertension and heart failure; however the current results of clinical trials are not encouraging. Synthetic B natriuretic peptide has demonstrated short-term hemodynamic improvement in patients, but in terms of renal function and long-term prognosis the effect was questionable. Nevertheless, new hope is ularitid a dual inhibitor of neprilysin and ARB: LCZ 696, the ongoing clinical studies and previous data from pilot studies appear promising., and Lenka Špinarová, Jindřich Špinar, Jiří Vítovec
Proteinuria is often used as a surrogate marker in monitoring and predicting outcome in patients with chronic kidney diseases, but it is non-specific. IgAN belongs to the most common primary glomerulonephritis worldwide with serious prognosis. The main aim of this work was to assess differences in urine proteins in patients with IgA nephropathy and to identify abnormal proteins as potential biomarkers of IgA nephropathy or the renal disease. In our pilot project, we selected 20 patients and compared them with 20 healthy volunteers. Protein quantification was performed using iTRAQ (isobaric tag for relative and absolute quantitation) labeling method. The peptides were separated by the isoelectric focusing method (IEF) and nano-LC with C18 column and identified by mass spectrometry using MALDI-TOF/TOF MS. Proteins´ lists obtained from IEF-LC-MS-MS/MS analysis were combined and contained 201 proteins. It was found out that 113 proteins were common in both experiments. 30 urinary proteins were significantly up- or down-regulated in patients with IgA nephropathy. We characterized potential biomarkers such as alpha-1-antitrypsin, apolipoprotein A-I, CD44 antigen or kininogen. Potential biomarkers of IgAN should be validated in further studies., P. Prikryl, L. Vojtova, D. Maixnerova, M. Vokurka, M. Neprasova, T. Zima, V. Tesar., and Obsahuje bibliografii
Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether ProvinolsTM, flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with ProvinolsTM, or with CsA and ProvinolsTM simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. ProvinolsTM restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms., R. Rezzani ... [et al.]., and Obsahuje seznam literatury
Příliš vysoký přívod sodíku je spojován s řadou zdravotních komplikací, především s hypertenzí. Data o spotřebě potvrzují vysoký přívod sodíku v mnoha zemích světa. Ve většině případů je daleko vyšší než uvádí doporučení (2 g sodíku/den). Hypertenze je významným rizikovým faktorem pro kardiovaskulární onemocnění a s nimi spojená úmrtí. Mnoho studií potvrdilo, že snížením přívodu sodíku dochází ke snížení tlaku krve (TK). U normotenzních jedinců není pokles TK tak významný jako u hypertenzních, přesto převládá názor, že i mírné snížení přívodu sodíku může mít dlouhodobý pozitivní vliv na zdraví populace. Odhady naznačují, že snížení denního přívodu sodíku o 3 g by mohlo snížit výskyt ischemické choroby srdeční (ICHS) o 10 % a výskyt cévní mozkové příhody (CMP) o 13 %. Reakce organismu na přívod sodíku může být různá. U některých osob dojde po snížení přívodu sodíku k výraznému poklesu tlaku krve. V souvislosti s tím se používá termín citlivost na sůl. Častěji se vyskytuje u starších osob a u Afroameričanů. Je podmíněná geneticky. Dalším onemocněním dávaným do souvislosti se sodíkem je onemocnění ledvin. Studie potvrdily vliv redukce přívodu sodíku na proteinurii a albuminurii. Přívod sodíku může mít vliv také na hypertrofii levé komory, nelze však s jistotou prokázat, zda jde opravdu o jev nezávislý na tlaku krve. Sůl a solené potraviny jsou označovány za pravděpodobnou příčinu nádorového onemocnění žaludku. Vysoký přívod soli může vyvolat atrofickou gastritidu a ovlivnit i další stadia patogeneze. Zvýšená spotřeba sodíku vede ke zvýšené exkreci vápníku močí. Výsledky studií zaměřených na potvrzení souvislosti mezi přívodem sodíku a dalšími ukazateli osteoporózy, jako jsou markery kostní resorpce nebo výskyt zlomenin, jsou však nekonzistentní. Ve starší literatuře se objevovaly zmínky o možné souvislosti sodíku a astmatu. Autoři nejnovější přehledové studie došli k závěru, že snížení přívodu sodíku nemá větší vliv na zlepšení astmatu. Téma sodíku je i přes množství realizovaných studií stále kontroverzní. K objasnění zůstává mnoho nejasných vztahů a příčinných souvislostí. I přes tyto nejasnosti se zdá, že snižování přívodu sodíku v populaci má význam., Excessive sodium intake is associated with many health complications, especially hypertension. Data on sodium intake show too high consumption in many countries around the world. In many cases sodium intake exceeds recommendation for adults, which is 2 g sodium/day. Hypertension is a major risk factor for cardiovascular disease and mortality. Many studies have confirmed that dietary sodium reduction reduces blood pressure (BP). BP reduction was less significant in normotensive individuals than in individuals with hypertension. Nevertheless, there is a consensus that even a moderate decreasing in sodium intake is likely to have a beneficial impact on public health. Estimates suggest that a reduction of 3 g of daily sodium intake would reduce ischemic heart disease by 10% and strokes by 13%. BP response to change in dietary sodium varies widely among individuals. Significant BP reduction is evident in some patients following decreased sodium intake. This heterogeneity led to a concept of salt sensitivity. It is more common among the elderly and African-Americans. Salt sensitivity is determined genetically. Another disease associated with sodium intake is kidney disease. Studies have confirmed the effect of reducing sodium intake on proteinuria and albuminuria. Sodium intake can affect left ventricular hypertrophy but it is impossible to prove whether it is independent of blood pressure. Salt and salted foods have been identified as a probable risk factor of stomach cancer. High salt intake can induce gastric atrophy and affect the other stages of pathogenesis. Increased consumption of sodium leads also to increased urinary calcium excretion. Relationship between sodium intake and other indicators like bone biomarkers or fractures is unclear. Some older studies suggest that dietary sodium can be related to asthma. Authors of the latest systematic review have concluded, that there is no evidence that reduction of sodium intake improves asthma control. Despite the number of completed studies, the question of sodium intake is still controversial. There is a plethora of unclear causal relationships. Regardless of these uncertainties, it seems that sodium intake reduction is beneficial for the population., Marie Šubrtová, Halina Matějová, and Literatura