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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 199 records · Page 11Linked to original sources
PubMed1996

Renal Na,K-ATPase in genetic hypertension.

Milan hypertensive rats (MHS) develop hypertension because of a primary renal alteration. Both apical and basolateral sodium transport are faster in membrane vesicles derived from renal tubules of MHS than in those of Milan normotensive control rats (MNS). These findings suggest that the increased renal sodium retention and concomitant development of hypertension in MHS may be linked to an altered transepithelial sodium transport. Since this transport is mainly under the control of the Na-K pump, we investigated whether an alteration of the enzymatic activity and/or protein expression of the renal Na,K-ATPase is detectable in prehypertensive MHS. We measured the Na,K-ATPase activity, Rb+ occlusion, turnover number, alpha 1- and beta 1-subunit protein abundance, and alpha 1 and beta 1 mRNA levels in microsomes from renal outer medulla of young (prehypertensive) and adult (hypertensive) MHS and in age-matched MNS. In both young and adult MHS, the Na,K-ATPase activity was significantly higher because of an enhanced number of active pump sites, as determined by Rb+ occlusion maximal binding. The higher number of pump sites was associated with a significant pretranslational increase of alpha 1 and beta 1 mRNA levels that preceded the development of hypertension in MHS. Since a molecular alteration of the cytoskeletal protein adducin is genetically associated with hypertension in MHS and is able to affect the actin-cytoskeleton and Na-K pump activity in transfected renal cells, we propose that the in vivo upregulation of Na-K pump in MHS is primary and linked to a genetic alteration of adducin.

Aging↗
PubMed1996

Hypertension may be transplanted with the kidney in humans: a long-term historical prospective follow-up of recipients grafted with kidneys coming from donors with or without hypertension in their families.

In several genetic hypertensive rat strains, transplantation studies have established that the kidney carries at least a portion of the genetic message for hypertension. In man it has, of course, been more difficult to obtain clearcut results. This historical prospective observational study, double-blinded for knowledge of donors' and recipients' family history for hypertension, concerns 85 transplanted patients, not treated with cyclosporine and with stable renal function, followed up for an average of 8 yr. Both the donors' and the recipients' families were carefully characterized for presence or absence of hypertension. After transplantation, in recipients without hypertension in their own families, a kidney coming from a "hypertensive" family determines less withdrawal and more introduction of antihypertensive therapy (AHT) than a kidney from a "normotensive" family (odds ratio for AHT introduction 5.0, confidence interval, 1.4 to 17.8; P = 0.017). In recipients with familial hypertension, the origin of the kidney does not influence the prevalence of hypertension after transplantation. More detailed analyses show that, in recipients without familial hypertension, the transplantation of a "hypertensive" kidney determines a tenfold larger increase in the requirement of antihypertensive therapy than the transplantation of a "normotensive" kidney, to obtain a similar blood pressure control (P = 0.003). This results is confirmed by the analysis of time-profile trends for antihypertensive therapy, adjusted for missing data, in the most clinically stable period (2nd to 10th yr after transplantation). The transmission of familial hypertension with the kidney is thus seen only in recipients coming from "normotensive" families, because a familial tendency for hypertension blunts the effect of receiving a "hypertensive" kidney.

Adult↗
PubMed1996

Triple therapy with azithromycin, omeprazole, and amoxicillin is highly effective in the eradication of Helicobacter pylori: a controlled trial versus omeprazole plus amoxicillin.

BACKGROUND: Azithromycin is a new-generation, acid-stable macrolide antibiotic that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a 5-day period after a single 500-mg oral dose. METHODS: We evaluated a new metronidazole-free triple therapy with omeprazole 20 mg b.i.d. plus amoxicillin 1 g b.i.d. (both for 14 days) and azithromycin 500 mg mane (for the first 3 days only) (group I) versus double therapy with omeprazole 20 mg b.i.d. plus amoxicillin 1 g t.i.d., both for 14 days (group II). H. pylori status was determined by urease test and histology before and 6 wk after completion of therapy. RESULTS: Ninety-two patients with peptic ulcer disease or nonulcer dyspepsia completed the study. H. pylori infection was eradicated in 44 (91.6%) of 48 patients randomized to receive triple therapy versus 26 (59.1%) of 44 who received double therapy (p < 0.001). Smoking, but not omeprazole pretreatment, proved to be a risk factor for treatment failure only in the double-therapy group (p = 0.05). All ulcers healed by the time of the 8-wk endoscopic control. Side effects, usually minor, were recorded in 12.5% and 9.1% of patients, respectively (NS), but therapy had to be discontinued in one patient in group I and in three in group II (NS). CONCLUSIONS: Two-week triple therapy with omeprazole, amoxicillin, and (for the first 3 days) low-dose azithromycin is highly effective in eradicating H. pylori. This regimen is safe and well-tolerated, and we recommend that it be used as first-line treatment, as an alternative to less-effective omeprazole-amoxicillin double therapy. Moreover, azithromycin appears to be a new, promising antibiotic for future innovative anti-H. pylori combinations.

Adult↗
PubMed1996

The galactose elimination capacity test: a study of the technique based on the analysis of 868 measurements.

OBJECTIVES: Our objective in this study was to analyze the correspondence of galactose concentration-on-time-decay curve to theoretical assumptions and the confidence limits of the determination of galactose elimination capacity. METHODS: We analyzed a retrospective series of 868 galactose elimination tests, performed on subjects with and without liver disease. Zero-order kinetics of galactose elimination was tested by comparison of the residual variance of linear regression with that obtained after quadratic transformation. The uncertainty in determination of galactose elimination capacity was calculated on the regression line by computing the 95% confidence limits of the estimate. RESULTS: The time-course of galactose concentration suggested an initial uneven distribution, and the first (20-min) data point deviated significantly from the regression. The galactose decay curve in plasma rejected linearity in 13% of tests; after exclusion of the first data-point, linearity was rejected in only 3% of cases. The 95% confidence interval of galactose elimination capacity was on average +/- 16%, but in individual tests it was as large as +/- 60-80%. The uncertainty of the test was not affected by linearity. It was larger, with poor fitting of the experimental data on the regression of galactose concentration on time, low number of data points, and low galactose elimination. It was maintained within +/- 20% only when residual variance was > or = 2% of total variance (nearly 50% of tests). CONCLUSION: The methodology for the determination of galactose elimination capacity leads to considerable uncertainty as to the final result, which must be considered whenever the test is used for clinical purposes in the decision-making process. It tends to be larger in patients with advanced disease and can be accurately calculated so as to contribute to a proper evaluation of the test result.

Adolescent↗
PubMed1996

Antihypertensive effects of lercanidipine in experimental hypertensive rats and dogs.

The antihypertensive action of lercanidipine (CAS 132866-11-6, Rec 15/2375), a new 1,4-dihydropyridine (1,4-DHP) calcium entry blocker (CEB), was examined in spontaneously hypertensive rats (SHR) and renal hypertensive dogs after acute and repeated administration, in comparison to several reference 1,4-DHPs. In acute experiments in SHR, lercanidipine reduced diastolic blood pressure showing a potency similar to felodipine and 2-3 fold higher than those of nicardipine and nitrendipine, after both intravenous and oral administration. Analysis of the area under the curves of percent reduction of diastolic blood pressure exerted for 3 and 8 h after intravenous and oral administrations, respectively, showed that the duration of the antihypertensive effect of lercanidipine was longer than that of the reference dihydropyridines. After repeated administrations to SHR no tachyphylaxis was observed, as indicated by the marked and persistent decrease in systolic blood pressure elicited by lercanidipine, given orally once a day for 21 days. Moreover, starting from the first week of treatment, the daily basal values of systolic blood pressure of the rats treated with lercanidipine were significantly lower than those of the placebo-treated group. In renal hypertensive dogs, after acute oral administration, lercanidipine was as potent as nitrendipine. After repeated administration, the action of lercanidipine was longer lasting than that of nicardipine and no decrease in the antihypertensive effects was observed. The in vivo studies show that lercanidipine has a potent and long-lasting antihypertensive profile, suggesting that this compound may be used for once-a-day treatment.

Administration, Oral↗
PubMed1996

Genetic determinants and renal mechanisms in essential hypertension.

Human essential hypertension is a polygenic disease whose phenotypic expression is modulated by the environment. Though the kidney could play a major role in the initiation and maintainment of hypertension, many questions remain open. Rat models of primary hypertension provided the substantial information with experiments on kidney cross-transplantation, showing that at least a portion of hypertension could be transplanted with the kidney in all strains where such an experiment has been carried out. Data consistent with those of rats have also been obtained in humans. Many abnormalities in kidney function and cell membrane ion transport have been described in hypertensive rats and humans, but the logical sequence of events from a genetic-molecular abnormality to a cellular abnormality which causes hypertension via a modification of kidney function is difficult to prove. We established this sequence in Milan hypertensive rats using a variety of experimental techniques such as the study of isolated kidney and renal cell function, cell membrane ion transport, cross-immunisation with membrane proteins, molecular biology, genetic crosses and manipulation. Such study led to the identification of a polymorphism in the cytoskeletal protein adducin. Recently, alpha-adducin variants have been associated to both primary hypertension and salt sensitive hypertension. Finally, recent findings strongly support the hypothesis that adducin variants may affect kidney function by modulating the overall capacity of the tubular epithelial cells to transport ions through both a modification in the assembly of actin cytoskeleton, and a modulation of sodium pump activity.

Animals↗
PubMed1995

Genomic organisation and chromosomal localisation of the gene encoding human beta adducin.

Adducin (ADD) is a heterodimeric protein of the membrane skeleton with subunits of 103 (alpha) and 97 kDa (beta). It promotes the assembly of the spectrin-actin network. We have previously shown that one point mutation in each of the alpha and beta rat ADD-encoding genes is associated with blood pressure variation in an animal model for hypertension, the Milan hypertensive strain of rats, probably due to a change in the phosphorylation pattern. In fact, the rat mutations, Y to F for alpha and R to Q for beta, are located, respectively, in a tyrosine kinase and a protein kinase A phosphorylation site. We have now determined, for the human beta-ADD-encoding gene, its chromosomal localisation, exon-intron organisation and alternative splicing patterns. We report here that human beta-ADD is localised on chromosome 2 and we also show a characteristic 3' end alternative splicing of the beta-ADD RNA that generates two distinct beta-ADD families, namely ADD 63 and 97; both of them in turn present a very complex differential splicing pattern in the internal exons.

Alternative Splicing↗
PubMed1995

(Ca+Mg)ATPase and calcium influx in erythrocytes of patients with idiopathic hypercalciuria.

Increased erythrocyte (Ca+Mg)ATPase activity was previously observed in idiopathic hypercalciuria. In order to verify if this alteration is a primary or a secondary event, we studied Sr influx in erythrocytes from subjects with idiopathic hypercalciuria. (Ca+Mg)ATPase activity was significantly higher in hypercalciuric than in hypercalciuric than in normocalciuric subjects whereas no difference in Sr influx was found between the two groups. (Ca+Mg)ATPase activity positively correlated with the erythrocyte Sr content found after 5 min of incubation and with urine Ca excretion. The normal Sr permeability suggests that (Ca+Mg)ATPase is primarily altered in idiopathic hypercalciuria. The primary increase of (Ca+Mg)ATPase activity may enhance passive Ca influx by reduction of cellular Ca concentration. It may induce a defect in cellular Ca metabolism that may cause idiopathic hypercalciuria by stimulating bone Ca turn-over and enteral Ca absorption.

Biological Transport↗
PubMed1995

Characterisation and chromosomal localisation of the rat alpha- and beta-adducin-encoding genes.

A polymorphism in the genes encoding alpha- and beta-adducin (ADD) was described as being associated with blood-pressure variation in a genetically hypertensive strain of rats (MHS). ADD is a cytoskeletal heterodimeric protein which may be involved in cellular signal transduction and interacts with other membrane skeleton proteins which affect ion transport across the cell membrane. The cDNA encoding the alpha subunit of rat ADD was isolated using PCR methods. The cDNA consists of about 3900 bp and encodes a protein of 735 amino acids (aa) which shows 91% aa identity with the human counterpart. In spleen and kidney, three alternative spliced exons were found by PCR amplification and confirmed by RNase protection analysis. 17 inbred rat strains were genotyped for the polymorphism in the alpha- and beta-ADD genes. Chromosomal localisation mapped rat alpha-ADD on chromosome 14 and rat beta-ADD on chromosome 4.

Alleles↗
PubMed1995

Effect of propionyl-l-carnitine and enalapril on cardiac function of pressure-overloaded rats during increase in load.

Chronic administration of propionyl-l-carnitine has been recently shown to correct hypertrophy related abnormalities in muscle mechanics. Accordingly, this study investigated whether the drug would similarly improve cardiac dynamics in rats with pressure overload. Enalapril was used for comparison. Drugs were administered in the drinking water for 3 weeks to Wistar Kyoto rats with a 2 week abdominal aortic constriction. Cardiac function was studied under urethane anaesthesia in basal conditions, during increase in preload, and during increase in afterload. Basal cardiac function was comparable in pressure-overloaded and sham-operated animals. Neither propionyl-l-carnitine nor enalapril affected the basal performance. Compared to sham-operated animals, untreated pressure-overloaded rats showed an impaired cardiac response (cardiac output, stroke volume) to preload increase induced by saline i.v. infusion. Propionyl-l-carnitine dose dependently improved cardiac function in the range 30-180 mg/kg, without affecting cardiac hypertrophic growth. Enalapril (3 mg/kg) reduced cardiac hypertrophy and improved cardiac function. The two effects were unrelated. The afterload increase by total aortic occlusion evidenced a reduction in the left ventricle pressure generating capacity of hypertrophied hearts. Propionyl-l-carnitine did not modify this parameter, while enalapril afforded a significant improvement. Results show that propionyl-l-carnitine significantly improves in vivo cardiac dynamics under conditions of increased energy demand. The effect is not due to inotropic efficacy, but presumably to increased cardiac efficiency.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Receptors, signal transduction, and spectrum of action of monocyte chemotactic protein-1 and related chemokines.

Chemokines are a bipartite family of chemotactic proteins that bear the structural hallmark of four cysteine residues, the first two of which are in tandem. The spectrum of action of C-C chemokines, monocyte chemotactic protein-1 (MCP-1), MCP-2, and MCP-3, in particular, encompasses, in addition to monocytes, other leukocyte populations. Evidence is presented that MCP-1, MCP-2, and MCP-3 are active on natural killer cells. Available information on receptor usage by MCP-1 and related chemokines and signal transduction pathways is reviewed. A better understanding of signaling mechanisms will provide a new basis for therapeutic strategies.

Calcium↗
PubMed1995

A genetic deficiency in calpastatin and isovalerylcarnitine treatment is associated with enhanced hippocampal long-term potentiation.

The Milan hypertensive strain (MHS) of rats, in addition to having hypertension, is also characterized by a genetic deficiency in calpastatin, the endogenous inhibitor of calpain. Since this protease has been implicated in long-term potentiation (LTP), we have investigated whether induction of this form of plasticity was altered in this strain of rats as compared to control animals (Milan normotensive strain, MNS). Progressive induction of LTP by increasing numbers of high frequency trains resulted in a greater degree of potentiation measured with all inducing protocols in MHS as compared with MNS animals. This difference was not related to the hypertension, since another hypertensive strain (the SHR strain) and a segregated Milan hypertensive strain, expressing only the hypertension but not the calpastatin deficiency (the MHNE strain), exhibited an LTP indistinguishable from control rats. Treatment of MHNE rats for 2 months with isovalerylcarnitine, a compound that increases calpain activity, also resulted in a greater amount of LTP induced by high frequency trains. These effects were not related to an enhancement of the NMDA receptor dependent component of responses to burst stimulation. These results are consistent with the idea that conditions under which calpain activation is facilitated are associated with a greater degree of synaptic potentiation.

Animals↗
PubMed1995

Thyroid volume in type 1 diabetes patients without overt thyroid disease.

An association between insulin-dependent diabetes mellitus (type 1) and thyroid diseases has long been reported, but the morphological evaluation of the thyroid in type 1 diabetes patients without overt thyroid disease has always been limited to physical examination. Ultrasonography of the thyroid gland was performed in 45 patients with type 1 diabetes without overt thyroid disease, to study thyroid volume and the prevalence of thyroid nodules. Data were compared with those obtained in 45 age- and sex-matched control subjects residing in the same area. In the patients, thyroid volume had increased on average by 46%; 35% of male and 32% of female patients had a thyroid volume exceeding the 95% confidence limits of the matched controls. The prevalence of thyroid nodules was only slightly raised. On average, free thyroxine was increased in the presence of normal triiodothyronine levels. Four patients were frankly hyperthyroid. The patients also showed a higher prevalence of thyroid-microsomal antibodies, but the thyroid hormone status was not different in relation to thyroid volume, nor was thyroid volume in relation to the presence of autoantibodies. Patients with type 1 diabetes without overt thyroid disorders may have morphological, ultrasonographically detectable alterations of the thyroid gland, the expression of a possible involvement of the thyroid in an autoimmune disorder not limited to the islet cells.

Adolescent↗