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At least 811 records · Page 45Linked to original sources
PubMed2002

Renin-angiotensin system genetic polymorphisms and cerebral white matter lesions in essential hypertension.

It has been reported that both the DD genotype of the angiotensin converting enzyme (ACE) gene and the presence of cerebral white matter lesions (WML) may represent risk factors for the development of stroke. The present study investigates a possible association between 3 different genetic polymorphisms of the renin-angiotensin system and the presence of WML in 60 never-treated essential hypertensive patients (36 men, 24 women), aged 50 to 60 years, without clinical evidence of target organ damage. All patients underwent brain magnetic resonance imaging to establish the presence or absence of WML. The insertion/deletion (I/D) ACE gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 receptor gene polymorphisms were determined by standard polymerase chain reaction. Twenty-five hypertensive patients (41.6%) were found to have WML on brain magnetic resonance imaging. No significant association between the M235T angiotensinogen or A1166C angiotensin II type 1 receptor genotypes and the presence of WML was found. However, the frequency of the DD genotype in patients with WML (64%) was significantly higher than that observed in patients without WML (28.6%; P=0.022). The DD genotype odds ratio for the presence of WML was 4.44 (95% confidence interval: 1.48 to 13.3). Likewise, the proportion of the D allele in patients with WML (74%) was significantly higher (P=0.014) than that observed in patients without WML (51.4%). We conclude that the presence of the DD genotype and/or the D allele of the ACE gene may be a predisposing factor for developing WML in essential hypertensive patients. However, because of the small sample size, these results require confirmation in a larger study.

Aged↗
PubMed2001

Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms.

We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. Seventy-one patients with essential hypertension were classified as salt sensitive or salt resistant by means of the 24-hour ambulatory blood pressure (BP) change to high salt intake. The polymorphisms evaluated correspond to the following genes: ACE (I/D), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C), 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) (G534A), aldosterone synthase (C-344T and Intron 2 conversion), and the mineralocorticoid receptor (G3514C and A4582C); all were determined using standard polymerase chain reaction methods. Thirty-five patients (49%) were classified as salt sensitive. We analyzed the BP response to high salt intake among genotypes and found a significant association for ACE I/D and 11betaHSD2 G534A polymorphisms. Patients homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake than did patients homozygous for the deletion allele (DD). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension was also significantly higher (P=0.003) in II (68%) and DI patients (59%) compared with DD hypertensives (19%). With respect to 11betaHSD2 G534A, patients with the GG genotype had a significantly higher systolic BP increase with high salt intake than did GA patients. In addition, plasma renin activity suppression in response to high salt was significantly greater in GA patients than in GG patients. The prevalence of salt-sensitive hypertension was 14.3% in GA patients and 50.8% in GG patients (P=0.067). In conclusion, the I allele of ACE I/D polymorphism is significantly associated to salt-sensitive hypertension. The BP response to high salt intake was different among genotypes of ACE I/D and 11betaHSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

Serum- and glucocorticoid-regulated kinase isoform-1 and epithelial sodium channel subunits in human ocular ciliary epithelium.

PURPOSE: In peripheral sodium-transporting tissues, the serum- and glucocorticoid-regulated kinase (SGK) isoform-1 is an early corticosteroid target gene in the activation of epithelial sodium channels (ENaCs). Sodium transport across the human ocular nonpigmented and pigmented ciliary epithelial bilayer (NPE-PE) is essential for aqueous humor production, but the expression of SGK1 and ENaC subunits remain to be defined. METHODS: SGK1 and ENaC subunits were evaluated by in situ hybridization and RT-PCR analysis on human NPE-PE sections and an NPE cell line (ODM-2). Northern blot analyses were conducted on ODM-2 cells incubated with dexamethasone (DEX) or aldosterone (ALDO) and RU38486 (a glucocorticoid receptor [GR] antagonist) or RU26752 (a mineralocorticoid receptor [MR] antagonist) or both inhibitors. The affinity of the GRs and MRs for DEX and ALDO was assessed by radioligand-binding assays. RESULTS: Expression of SGK1 and ENaC subunits was confirmed in NPE-PE tissues and ODM-2 cells. Dose-dependent induction of SGK1 mRNA in the ODM-2 cells was demonstrated after incubation with DEX or ALDO. While response to DEX was not inhibited by RU38486 or RU26752, there was a moderate reduction in induction by ALDO in the presence of RU26752 that was completely abolished in the presence of both inhibitors. Specific binding of (3)[H]DEX and (3)[H]ALDO was established, revealing greater expression of GRs than MRs. CONCLUSIONS: The expression of ENaCs within the NPE-PE and corticosteroid regulation of SGK1 through the GR and MR, indicate that this mechanism may be a feature of sodium transport in the human ocular ciliary epithelium.

Aldosterone↗
PubMed2004

Identification of target genes regulated by FOXC1 using nickel agarose-based chromatin enrichment.

PURPOSE: To overcome the problem of antibody availability, often encountered during chromatin immunoprecipitation (ChIP) assays, nickel agarose-based chromatin enrichment (NACE) was developed. Based on the affinity of (His)-6-tagged proteins for the nickel ion, this modified form of ChIP allows the isolation of chromatin in the absence of specific antibodies. METHODS: Nonpigmented ciliary epithelium cells were transfected with (His)-6-tagged FOXC1. FOXC1-enriched chromatin complexes were isolated by using the tight electrostatic interaction between histidine residues of the recombinant FOXC1 protein and nickel. One hundred fifty NACE-enriched clones were sequenced and subjected to in silico and biochemical analyses. RESULTS: Twenty-six clones were detected near known genes: Eight were near predicted but uncharacterized genes, eight were within areas where neither known nor predicted genes have yet been mapped, four were chimeric, and the rest were either repetitive (n=81) or poor-quality (n=23) sequences. Twenty of the 26 known genes were expressed in the eye. Five of the NACE-enriched clones (BMP2K, DACH, FVT-1, SIX-1, and PGE-2 receptor), as well as nine clones selected from the literature, were validated by PCR amplification in two independent lots of NACE-enriched chromatin. All five NACE-selected genes were detected in two independent assays, as well as four (BMP7, SMAD2, TGF-B1, and WNT6) of the nine genes selected from the literature, consistent with these genes' being regulated by FOXC1. CONCLUSIONS: NACE is a useful technique allowing specific chromatin enrichment in cases where antibodies are unavailable. Specific recovery of PTGER, DACH1, WNT6, and FVT-1 implicates FOXC1 in a variety of cellular events including modulation of intraocular pressure, cell cycle, ocular development, and oncogenesis.

Chromatin↗
PubMed2005

Selective upregulation of the A3 adenosine receptor in eyes with pseudoexfoliation syndrome and glaucoma.

PURPOSE: Adenosine is increasingly released in metabolic stress conditions, like hypoxia or ischemia, and regulates many physiologic processes, such as aqueous humor secretion and intraocular pressure, via activation of four adenosine receptors. In the current study, the role of the adenosine system in the pathophysiology of pseudoexfoliation (PEX) syndrome, which is typically associated with anterior chamber hypoxia and elevated intraocular pressure, was examined. METHODS: RT-PCR, Northern hybridization, in situ hybridization, and immunohistochemistry were applied to analyze the mRNA and protein expression of the adenosine receptor subtypes A1, A2A, A2B, and A3 in anterior segment tissues of PEX eyes, without and with glaucoma, in comparison to eyes with primary open-angle or angle-closure glaucoma and normal control eyes. Real-time PCR was used to study the effect of hypoxia and oxidative stress on adenosine receptor expression by nonpigmented ciliary epithelial cells in vitro. Levels of adenosine and its catabolites inosine, hypoxanthine, and xanthine were measured in cell culture supernatants and aqueous humor samples by HPLC. RESULTS: All four adenosine receptor subtypes (A2A > A1 > A2B > A3) were coexpressed but differently distributed in the ciliary epithelium of control eyes, with the A3 receptor being localized to the basolateral membrane infoldings of the nonpigmented epithelial cells. A selective, approximately 10-fold upregulation of A3 receptor mRNA and protein was consistently found in the nonpigmented ciliary epithelium of all PEX eyes, with and without glaucoma, compared with the normal and glaucomatous control eyes. Significant upregulation of A3 receptor message in nonpigmented epithelial cells was induced by both hypoxia and oxidative stress in vitro, together with increased levels of inosine, hypoxanthine, and xanthine in the supernatants. Levels of adenosine and its catabolites, however, were not significantly elevated in the aqueous humor of patients with PEX. CONCLUSIONS: Considering the known role of the A3 adenosine receptor in modulating aqueous humor secretion, its selective, probably hypoxia-induced upregulation in the ciliary epithelium may not only confer cytoprotection but also influence aqueous humor dynamics and may be accessible to therapeutic intervention in patients with PEX.

Adenosine↗
PubMedDate not supplied

Persistence of tumor DNA in plasma of breast cancer patients after mastectomy.

BACKGROUND: We investigated tumor DNA changes before and after mastectomy in the plasma of breast cancer patients with no disseminated disease and eventually investigated these changes' relationship to specific pathological parameters of the tumors. METHODS: We studied 41 patients. DNA extracted from tumor and normal breast tissues, mononuclear blood cells, and plasma was used for molecular studies. Alterations in the microsatellite markers D17S855, D17S654, D16S421, TH2, D10S197, and D9S161, as well as point mutations in the p53 gene and aberrant methylation of p16(INK4a), were used to identify and characterize tumor and plasma DNA. A number of tumor clinicopathological parameters were analyzed in each patient. RESULTS: We found that 18 (44%) of the 27 patients with alterations in tumor DNA presented the same plasma DNA alteration before mastectomy, and persistence of the same molecular features was detected in plasma DNA 4 to 6 weeks postmastectomy in 8 (19.5%) patients. Patients with vascular invasion, more than three lymph node metastases, and higher histological grade at diagnosis displayed plasma DNA after mastectomy with a significant difference. CONCLUSIONS: Persistence of plasma DNA with features of tumor DNA may be present after mastectomy in breast cancer patients, and its relation to bad-prognosis histological parameters may suggest undetectable micrometastatic disease.

Biomarkers, Tumor↗
PubMed2003

Trandolapril in left ventricular dysfunction after myocardial infarction: focus on the TRACE study.

The new angiotensin-converting enzyme (ACE) inhibitor trandolapril has been the subject of a broad pharmacological and clinical development program. The active metabolite, trandolaprilat, has been found to have a high level of affinity for angiotensin-converting enzyme. Trandolapril has demonstrated potent ACE inhibition, a long plasma half-life and a high degree of lipophilicity. The drug has been used to treat patients with mild-to-moderate hypertension and congestive heart failure following myocardial infarction. In the former patients, a once-daily dosage of trandolapril has produced significant and long-lasting reductions in blood pressure and has reduced left ventricular hypertrophy. Trandolapril is one of a few ACE inhibitors with a mean trough:peak ratio of blood pressure reduction with once-daily administration of over 50%. In addition, studies in hypertensive patients have revealed still greater reductions in blood pressure when trandolapril is combined with the calcium antagonist verapamil. In patients with left ventricular dysfunction after myocardial infarction, the large TRACE trial showed that mortality was reduced and life expectancy increased with trandolapril treatment.

Animals↗
PubMed1990

Pulsed Doppler echocardiography in the diagnosis of pulmonary hypertension in COPD.

We used pulsed Doppler echocardiography to examine the systolic ejection flow from the right ventricle in 66 patients with chronic obstructive pulmonary disease. Adequate recordings were obtained in 60 patients, in conjunction with right heart catheterization. Patients without pulmonary artery hypertension at rest (mean pulmonary artery pressure less than 20 mm Hg) underwent an exercise test which identified a group with PAH during exercise (MPAP greater than 30 mm Hg). The patients were divided into four groups: group 1, or control group: 17 healthy nonsmokers without normal respiratory function data; group 2: COPD without PAH (n = 12); group 3: PAH during exercise (n = 26); group 4: PAH at rest (n = 22). Analysis of Doppler data included time to peak velocity, right ventricular pre-ejection period, and ejection period. Pulsed Doppler echocardiography was a simple and reliable method of detecting PAH. Latent PAH, revealed by the exercise test, was accompanied by significant changes in Doppler findings, confirming the sensitivity of the method.

Cardiac Catheterization↗
PubMed2005

Adverse cardiorenal effects of aldosterone: is aldosterone antagonism beneficial?

Aldosterone has recently been recognized as an important factor in the development and progression of cardiorenal disease. Animal and human data suggest that aldosterone contributes importantly to several disease states. These include congestive heart failure, coronary heart disease and progression of kidney disease. Recently, the discovery that aldosterone antagonists decrease pathologic injury in the kidneys and nonepithelial tissues, such as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. The available data is reviewed and conclusions drawn regarding the relative benefits of modulating aldosterone effects in the cardiovascular system and the kidney. In particular, the authors review their effects on reductions in cardiovascular events and progression of chronic kidney disease, as well as the safety and tolerability of these agents.

Aldosterone↗
PubMed2006

Seroepidemiological study of herpes simplex virus type 2 in patients with the acquired immunodeficiency syndrome in the city of Niterói, Rio de Janeiro, Brazil.

This study was designed to determine the seroprevalence of herpes simplex virus type 2 (HSV-2) and to evaluate its association with age, sex as well as other demographic and behavioural factors in 150 human immunodeficiency virus (HIV) positive adults patients attending the general medical outpatient ward for routine care of Niterói, state of Rio de Janeiro, Brazil. Serum samples were screened for HSV-2 antibodies using an indirect ELISA. Eighty-three patients were men (mean age: 38.8) and 67 were women (mean age: 35.4). The estimated prevalence of HSV-2 was 52% (95% CI: 44-60%) and it was higher among men (53%) than among women (50.7%). Overall, the age of first sexual intercourse and past history of genital herpes were associated with HSV-2 seropositivity. Analysis by gender disclosed significant association of number of lifetime sex partners only among men. Although HSV-2 antibodies were frequent in the study group, genital herpes was reported by 21.8% of the HSV-2 positive subjects, indicating low awareness of the HSV-2 infection. These results may have public health importance for Brazil as the high rate of HSV-2 infection may act as a cofactor of HIV transmission.

Adult↗
PubMedDate not supplied

Histological development of the vomeronasal complex in the pre- and postnatal rat.

The vomeronasal complex of the rat was studied by means of different staining techniques and light microscopy between the 13th day of gestation and 42 days of postnatal life. The anlage of the vomeronasal organ in the 13-day-old embryo consisted of a cluster of cells proliferating from the olfactory placode towards the medial line. The vomeronasal organ was well developed by the end of gestation, showing the same ratio between receptor and receptor-free epithelium as in the adult animal. However, full development of the epithelia did not occur until the end of the second postnatal week. Glandular rudiments were observed within the vomeronasal area in 17-day-old fetuses, but the gland showed no sign of activity until the 7th day of postnatal life, when a slight PAS-positive reaction was observed in their cells' cytoplasm. This PAS-positive reaction intensified considerably during the second week and corresponded to the adult picture by the end of this time. The content of the vomeronasal glands contrasted with that of the glands flowing into the nasal fossa, which did not show any PAS-positive reaction but which stained positive for alcian blue. We also studied the evolution of the blood vessels such as the capsule of the complex. This capsule showed complete ossification by the beginning of the 3rd postnatal week, with the exception of certain regions which remained cartilaginous in the adult. Some capillaries were observed in the complex in 17-day-old fetuses, and by 20 days of gestation some of them could be observed penetrating the receptor epithelium. Subsequently, the vascularization of the complex became so profuse that one could consider the vomeronasal complex to consist of erectile tissue.

Animals↗
PubMed1991

Antidiuretic hormone and renal function after water loading in patients with cirrhosis of the liver.

Renal function and plasma antidiuretic hormone (ADH) levels were studied basally and after oral water load in four groups of subjects: 15 healthy controls (group I), 15 cirrhotics without ascites (group II), 15 cirrhotics with ascites (group III), and 10 decompensated cirrhotics with hyponatremia (group IV). Renal function and ADH levels were normal in group II. In groups III and IV water diuresis and fractional proximal sodium excretion were significantly decreased, whereas fractional distal sodium resorption and fractional excretion of potassium did not differ from those of controls. Basal ADH was significantly increased only in patients of group IV. In these patients ADH remained abnormally high after water loading. ADH did not correlate with water diuresis, plasma osmolality, mean arterial pressure, and plasma renin activity. We conclude that impaired water excretion in decompensated cirrhotics without hyponatremia cannot be ascribed to high serum levels of ADH. On the contrary, it seems to be related mainly to a reduced delivery of filtrate to the diluting segment of the nephron. In cirrhotic patients with hyponatremia high levels of ADH may play an additional role.

Adult↗
PubMed1989

Intracellular voltage recordings in bovine non-pigmented ciliary epithelial cells in primary culture.

Bovine non-pigmented ciliary epithelial cells (NPE) have been isolated by a technique of selective adhesion to tissue culture plastic. NPE cells in primary culture proliferated and maintained epithelial-like morphology for about 4 weeks in tissue culture medium containing 10% fetal calf serum. If grown for longer than 4 weeks in serum-containing medium, cells changed their morphology and became elongated and spindle-shaped. Membrane potentials were measured using conventional microelectrodes. In NPE cells of epithelial-like shape, replacing extracellular Na+ induced a transient hyperpolarization of the membrane potential, while in elongated cells of spindle-shaped morphology an immediate depolarization was observed. We therefore only used epithelial-like NPE for further experiments. In these cells the mean membrane potential was -40.3 +/- 0.5 mV (n = 36). Relative K+ conductance was increased by extracellular alkalinization. Removing extracellular K+ led to a depolarization and readdition of K+ to K+ depleted cells resulted in a hyperpolarization. Both voltage responses were sensitive to ouabain, indicating that Na+/K+ ATPase is inhibited by K+ replacement, and that there is overshoot-activation of the pump when K+ is readded. Extracellular Cl- replacement led to a DIDS sensitive, transient depolarization, which is compatible with a stilbene-sensitive Cl(-)-conductance. Removing HCO3- led to a Na+ dependent and DIDS-sensitive depolarization. However, the electrical response on replacement of extracellular Na+ was not influenced by DIDS or the extracellular HCO3(-)-concentration.

Acetylcholine↗
PubMed1991

Detection and characterization of Ca(2+)-activated K+ channels in transformed cells of human non-pigmented ciliary epithelium.

Cell-attached and excised inside-out membrane patches were used to study single channel currents in a cell line derived from human non-pigmented ciliary epithelium. Most of the patches contained a Ca(2+)-dependent K+ channel with large unitary conductance (200 pS in symmetrical K+ solutions). Single channel current in cell-attached patches exposed to high K+ solution in the pipette showed a null potential of -36 mV. This value, which should yield an approximate estimation of cell membrane potential, was reversibly increased by -30 to -40 mV in the presence of Ca2+ ionophores. Tetraethylammonium up to 10 mM applied at the membrane cytoplasmic face had no effect on the channel. Addition of 1 mM BaCl2 to excised patches caused a voltage-dependent blockade of the channel. In the presence of barium the unit currents were not altered, but the channel remained closed for long periods of time and the open state probability decreased with depolarization. The possibility that this channel participates in regulation of transepithelial ciliary body secretion is discussed.

Calcium↗