Recent aspects in the genetic renal mechanisms involved in hypertension.
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The kidney plays an important role in the blood pressure regulation primarily by modulating tubular sodium reabsorption. Various hormones, vasoactive peptides, autacoids and transporters or channels in renal tubules are involved in this process. Genes associated with renal tubular sodium handling are possibly related to the development of hypertension. Genes of the renin-angiotensin-aldosterone system are thought to be especially important as causal genes of hypertension. Na-K-ATPase, biochemically equal to Na pump, exists on the basolateral membrane of renal epithelial cells. It plays a central role in Na reabsorption and creates a driving force for transepithelial transport. Na-K-ATPase activity is regulated by adducin, a membrane-bound skeletal protein, as well as by several hormones such as dopamine, endogenous ouabain-like factor or cytochrome P450 metabolites. Genes of these factors involved in Na-K-ATPase regulation should be related to the development of hypertension. The endothelin system, atrial natriuretic peptide and nitric oxide regulate the tonus of blood vessels as well as renal sodium excretion. Several reports have indicated that genes of these substances are crucial in the pathogenesis of hypertension. (+info)
Increased digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy.
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AIMS: Although increased digitalis-like immunoreactive substances have been found in cases of hypertension and heart failure, no information is available about digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy. We investigated digitalis-like immunoreactive substances in the plasma and biopsied specimens of patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: In 40 patients with hypertrophic cardiomyopathy (27 with the non-obstructive type and 13 with the obstructive type), the plasma concentration of digitalis-like immunoreactive substances was studied by fluorescence polarization immunoassay. Right ventricular endomyocardial biopsy specimens were analysed immunohistochemically, using a monoclonal antibody against digoxin. An increase in digitalis-like immunoreactive substances of more than 0.2 ng. ml(-1)in plasma was found in six of 27 patients with non-obstructive hypertrophic cardiomyopathy (22.2%) and five of 13 with obstructive hypertrophic cardiomyopathy (38.4%). Under light microscopy, positive staining against the antibody was observed heterogeneously on some cardiocytes. In non-obstructive hypertrophic cardiomyopathy, digitalis-like immunoreactive substances in the plasma correlated with the left atrial dimension and inversely with the cardiac index. In obstructive hypertrophic cardiomyopathy, plasma and myocardial digitalis-like immunoreactive substances were positively correlated; they also correlated with left ventricular end-diastolic pressures. Under electron microscopy, digitalis-like immunoreactive substances were detected at the sarcolemma in the free wall, T-tubules, intercalated discs and Z-bands of cardiocytes. CONCLUSIONS: Increased digitalis-like immunoreactive substances in plasma and cardiocytes, which may have been caused by pressure and/or volume overload, were found in patients with hypertrophic cardiomyopathy. Digitalis-like immunoreactive substances may act on the sarcolemma of cardiocytes and be transported into the cytoplasm. (+info)
Saposins A, B, C, and D in plasma of patients with lysosomal storage disorders.
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BACKGROUND: Early diagnosis of lysosomal storage disorders (LSDs), before the onset of irreversible pathology, will be critical for maximum efficacy of many current and proposed therapies. To search for potential markers of LSDs, we measured saposins A, B, C, and D in patients with these disorders. METHODS: Four time-delayed fluorescence immunoquantification assays were used to measure each of the saposins in plasma from 111 unaffected individuals and 334 LSD-affected individuals, representing 28 different disorders. RESULTS: Saposin A was increased above the 95th centile of the control population in 59% of LSD patients; saposins B, C, and D were increased in 25%, 61%, and 57%, respectively. Saposins were increased in patients from several LSD groups that in previous studies did not show an increase of lysosome-associated membrane protein-1 (LAMP-1). CONCLUSION: Saposins may be useful markers for LSDs when used in conjunction with LAMP-1. (+info)
Particulate adjuvants can induce macrophage survival, DNA synthesis, and a synergistic proliferative response to GM-CSF and CSF-1.
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The mode of action of immunological adjuvants is not yet completely understood. Many are particulate. Certain antigen-presenting (dendritic) cell populations belong to the monocyte/macrophage lineage and, like other members of the lineage, in some tissues appear to be short-lived. We report that many poorly degradable, particulate adjuvants, for example, aluminum hydroxide, oil-in-water emulsions, calcium phosphate, and silica, enhance murine bone marrow-derived macrophage survival; induction of DNA synthesis was even observed. No evidence could be found for a requirement for endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage-CSF (M-CSF or CSF-1). Synergy for the proliferative effects was noted in the presence of added GM-CSF or CSF-1. It is suggested from these in vitro findings that one function of certain particulate adjuvants may be to increase by enhanced survival or even proliferation the number of cells available for subsequent antigen presentation and cytokine production. (+info)
Interleukin-13 prevents diaphragm muscle deterioration in a septic animal model.
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The effects of an intravenous injection of Interleukin-13 (IL-13) after endotoxin administration on diaphragm muscle were studied using Wistar rats. Two treatment groups, a control (saline+endotoxin) group and an IL-13 (IL-13+endotoxin) group were studied. E. coli endotoxin (10 mg/kg) was injected intraperitoneally 5 minutes after saline or IL-13 (0.25 microg) injection. The force-frequency curves, twitch kinetics and fatigability were measured at 0 and 4 hours after endotoxin injection. The force-frequency curves and twitch tension in the control group were significantly lower at 4 hours than those at 0 hour due to endotoxin. On the other hand, IL-13 prevented the decrement of the force-frequency curves and twitch tension induced by endotoxin. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry showed positive staining at 4 hours due to endotoxin in the control group; however, IL-13 also blocked NADPH diaphorase staining at 4 hours. Furthermore, the positive muscle fibers detected by the NADPH diaphorase staining were classified as type I (slow twitch) muscle fibers by ATPase staining. We conclude that IL-13 prevents the deterioration of contraction induced by endotoxin by inhibiting nitric oxide production in the diaphragm muscle, mainly the type I muscle fibers. (+info)
Hypotensive effect of tenuifolic saponin and its mechanism.
(30/1244)
AIM: To study the effect of tenuifolic saponin (TS) on arterial pressure. METHODS: Mean arterial pressure (MAP) was recorded from left carotid artery in rat which was anesthetized with urethane and then injected i.v. gtt with a transfusion of NaCl 0.15 mol.L-1. Systolic blood pressure (SBP) of conscious rat and renovascular hypertensive rat (RVHR) was measured by tail cuff method. RESULTS: TS 2, 4, 8 mg.kg-1 i.v., 20 and 40 mg.kg-1 i.g. reduced the MAP by 31%, 37%, 50%, 21%, and 31%, respectively. Bilateral vagotomy plus atropine (Atr) i.v., or pretreatment with diphenhydramine hydrochloride (Dip) failed to influence TS effect. Lack of effect of TS on carotid-occlusion-induced- or epinephrine (Epi)-induced-hypertensive response was found. SBP in conscious rat and RVHR was suppressed, highest by 38.0% and 26.8% at 60 and 90 min, maintaining at least 2 and 3 h, respectively, after i.g. TS 40 mg.kg-1. CONCLUSION: TS reduced the arterial pressure, not related to vagus excitation, ganglionic blockade, and peripheral alpha-adrenergic-, M-cholinergic-, and H1-receptors. (+info)
Anti-inflammatory effects of total saponins of Panax notoginseng.
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AIM: To study the anti-inflammatory effects of total saponins of Panax notoginseng (PnS). METHODS: Rat air-pouch acute inflammatory model was established with s.c. carrageenan (Car, 25 mg.kg-1). The protein content in exudate was measured. Micro-acid titration assay and radioimmunoassay (RIA) were applied respectively to investigate effects of PnS on phospholipase A2 (PLA2) activity and dinoprostone (Din) content in exudate. Fura-2 fluorescence technique was used to determine the intracellular free calcium concentration in neutrophils (Neu-[Ca2+]i). RESULTS: At 12 h, PnS 60-240 mg.kg-1 i.p. reduced Neu counts, protein content [(7.7 +/- 1.3) to (4.4 +/- 1.4) g.L-1], and Din content [(1619 +/- 391) to (883 +/- 268) ng.L-1]; inhibited the PLA2 activity in exudate [(248 +/- 42) to (157 +/- 35) kU.L-1] in a dose-dependent manner. PnS 60, 120, and 240 mg.kg-1 lowered the level of Neu-[Ca2+]i with the inhibitory rate of 9.1%, 33.2%, and 39.4%, respectively. CONCLUSION: PnS has an obvious anti-inflammatory effect and its mechanisms are related to the inhibition of the Neu-[Ca2+]i level and PLA2 activity, and reduction of Din content. (+info)
Effect of aerobic exercise and ginsenosides on lipid metabolism in diet-induced hyperlipidemia mice.
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AIM: To study the effect of aerobic exercise and its combination with Gin (ginsenosides from stems and leaves of ginseng) on lipid metabolism in diet-induced hyperlipidemia mice. METHODS: The mouse hyperlipidemia model was set up by feeding high cholesterol diet. Unloaded swimming was designed to be a manner of aerobic exercise. The effects of aerobic exercise and its combination with Gin on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c) in serum, malondialdehyde (MDA), and superoxide dismutase (SOD) in liver tissue were measured; the thymus and liver were weighed. RESULTS: (1) The mouse hyperlipidemia model was set up successfully: TC and MDA increased (P < 0.05) but HDL-c and SOD decreased (P < 0.05); the liver weight increased and the thymus weight reduced; fatty liver was found; (2) aerobic exercise reduced TC but increased MDA and HDL-c in cholesterol-rich diet mice; the liver weight did not reduce, and fatty liver did not clear up; and (3) when aerobic exercise combined with Gin, TC and TG decreased markedly (P < 0.01), and MDA also decreased (P < 0.05); SOD and HDL-c increased markedly (P < 0.01); the thymus weight increased and the liver weight decreased to normal level; fatty liver cleared up. CONCLUSION: Aerobic exercise could lower serum lipid to some extent but could not satisfactorily regulate lipid metabolism. When combined with Gin, aerobic exercise could better lower serum lipid, regulate lipid metabolism, promote antioxidation, and enhance immune activity. (+info)