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Biomedical subjects

P Gentilini

Publications and source records attributed to P Gentilini.

At least 19 recordsLinked to original sources
PubMed1992

Plasma levels of brain natriuretic peptide in patients with cirrhosis.

Plasma levels of brain natriuretic peptide, a recently identified cardiac hormone with natriuretic activity, were measured in 11 healthy subjects, 13 cirrhotic patients without ascites, 18 nonazotemic cirrhotic patients with ascites and 6 patients with cirrhosis, ascites and functional kidney failure. Plasma levels of brain natriuretic peptide were similar in healthy subjects and cirrhotic patients without ascites (5.56 +/- 0.65 and 7.66 +/- 0.68 fmol/ml, respectively). In contrast, cirrhotic patients with ascites, with and without functional kidney failure, had significantly higher plasma concentrations of brain natriuretic peptide (19.56 +/- 1.37 and 16.00 +/- 1.91 fmol/ml, respectively) than did healthy subjects and patients without ascites (p less than 0.01); no significant difference was found between the two groups of cirrhotic patients with ascites with respect to this parameter. In the whole group of cirrhotic patients included in the study, brain natriuretic peptide level was directly correlated with the degree of impairment of liver and kidney function, plasma renin activity and plasma levels of aldosterone and atrial natriuretic peptide. The results of this study indicate that brain natriuretic peptide is increased in cirrhotic patients with ascites and suggest that sodium retention in cirrhosis is not due to deficiency of this novel cardiac hormone.

Alanine Transaminase↗
PubMed1992

Thromboxane-receptor blockade increases water diuresis in cirrhotic patients with ascites.

This study was undertaken to investigate the role of increased renal thromboxane (TX) A2 production in modulating renal hemodynamics and sodium and water retention in cirrhotic patients with ascites. In a randomized, double-blind, placebo-controlled, crossover trial, 15 nonazotemic cirrhotic patients with ascites and elevated urinary TXB2 excretion received the thromboxane-receptor antagonist ONO-3708 (3 micrograms.kg-1.min-1) in a 4-hour continuous infusion. Administration of ONO-3708 significantly blocked TXA2 receptors; bleeding time showed a twofold increase (432 +/- 65 vs. 131 +/- 17 seconds; P less than 0.005), and platelet aggregation to U-46619 (an agonist of TXA2 receptors) was abolished in all patients studied. The drug induced a significant increase in free water clearance (3.06 +/- 0.70 vs. 1.72 +/- 0.57 mL/min; P less than 0.001) and diuresis (4.74 +/- 0.79 vs. 3.94 +/- 0.66 mL/min; P less than 0.05) compared with placebo, as well as a significant (14%) increase in renal plasma flow. The increases in both free water clearance and diuresis induced by ONO-3708 were directly related to basal urinary TXB2 excretion. These results suggest a role for renal TXA2 as a modulator of water handling in cirrhotic patients with ascites.

Aged↗
PubMed1992

Infection of peripheral mononuclear blood cells by hepatitis C virus.

We investigated the infection of peripheral blood mononuclear cells (PBMNC) by hepatitis C virus (HCV) in 5 patients with HCV-related chronic hepatitis. The presence of HCV-RNA-positive and -negative strands was tested with the polymerase chain reaction (PCR) method. In all subjects, HCV-RNA was shown in PBMNC. In 3 cases, HCV-RNA was shown in the T- and B-cell populations, with viral RNA also present in the monocyte-macrophage fraction of two of these. HCV-RNA-negative stranded molecules, indicative of the viral multiplication, were significantly increased in cells maintained in cultures with PHA/PMA stimulation. The results indicate that HCV infect blood mononuclear cells, thus suggesting that this cellular tropism may play a role in HCV infection.

Adult↗
PubMed1992

Phenotypical modulation of liver fat-storing cells by retinoids. Influence on unstimulated and growth factor-induced cell proliferation.

In conditions of chronic liver inflammation, liver fat-storing cells (FSC) differentiate into 'myofibroblast-like cells'. This transition is characterized by a gradual loss of vitamin A stores, and previous studies suggest a possible relationship between the intracellular retinoid content and the proliferative potential of this cell type. In the present study, we further characterized this aspect of FSC biology by monitoring ultrastructural changes and growth characteristics during several serial passages in culture. Our observations suggest that the complete transition to the 'myofibroblast-like phenotype' is paralleled by a sudden and remarkable increase in the growth rate. At this stage, cell growth appears rather independent from the presence of mitogens in the culture medium, suggesting cell transformation. Accordingly, the mitogenic effects of platelet-derived growth factor and epidermal growth factor appears reduced when compared to those observed in FSC retaining the original 'storing' phenotype. Incubation of vitamin A-depleted FSC with retinol and retinoic acid resulted in the partial recovery of intracellular retinoid stores and in a significant reduction of basal growth rate and basal and growth factor-induced DNA synthesis. In summary, these in vitro observations suggest that intracellular retinoids play a central role in the control of unstimulated and growth factor-induced FSC proliferation and may help understand in vivo mechanisms leading to liver fibrosis.

Analysis of Variance↗
PubMed1992

Pathophysiology and treatment of ascites and the hepatorenal syndrome.

Ascites indicates the accumulation of fluid in the peritoneal cavity, due to a wide range of causes. These causes can be classified according to the presence of portal hypertension, severe blood dyscrasia and peritoneal disease. Cirrhosis is the most frequent cause of ascites. The occurrence of ascites in cirrhosis is due to portal hypertension, which is responsible for the increase in hydrostatic pressure at the sinusoidal level and the alterations of splanchnic and systemic haemodynamics. These latter include increased splanchnic inflow, reduced systemic resistance and increased plasma volume and cardiac output. Portal hypertension also plays a major role in determining sodium retention, which occurs in the setting of increased RAA system and SNS activity. The mechanisms by which portal hypertension leads to the activation of antinatriuretic factors and sodium retention are not completely understood; three main hypotheses have been proposed to explain this relationship, namely the underfilling, the overflow and the peripheral arterial vasodilatation theories. In patients with cirrhosis and ascites, there is an overall activation of the renal prostaglandin system, which probably acts to maintain renal haemodynamics and GFR by counteracting the vasoconstricting effects of AII and noradrenaline on renal circulation. In advanced stages, ascites may become refractory to medical treatment and renal function shows a progressive impairment and eventually acute renal failure, the so-called HRS, due to a marked vasoconstriction of the renal arteries and the opening of the intrarenal-arteriovenous (A-V) shunts. In this condition, the reduced renal synthesis of vasodilating prostaglandins is probably of pathogenic importance. Treatment of ascites is usually based on bed rest, low-sodium diet and administration of aldosterone antagonists and loop diuretics. A sequential treatment of ascites based on the progressive addition of more potent drugs is the best way to relieve ascites while avoiding potentially dangerous side-effects. Patients who fail to respond to the above manoeuvres are said to have refractory ascites. Current treatment of this latter condition is mainly based on therapeutic paracentesis and the application of the LeVeen shunt, but long-term results are unsatisfactory.

Ascites↗
PubMed1992

Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients.

Liver perisinusoidal fat-storing cells (FSC) show morphological and ultrastructural characteristics similar to pericytes regulating local blood flow in other organs. In the present study we have analyzed whether FSC respond to local vasoconstrictors such as thrombin, angiotensin-II, and endothelin-1 with an increase in intracellular free calcium concentration ([Ca2+]i) coupled with effective cell contraction. All agonists tested induced a rapid and dose-dependent increase in [Ca2+]i followed by a sustained phase lasting several minutes in confluent monolayers of Fura-2-loaded human FSC. Pharmacological studies performed using different Ca2+ channel blockers indicated that, at least for thrombin and angiotensin-II, the sustained phase is due to the opening of voltage-sensitive membrane Ca2+ channels. To analyze the temporal and spatial dynamics of Ca2+ release in response to these agonists, we performed experiments on individual Fura-2-loaded human FSC using a dual wavelength, radiometric video imaging system. The rise in [Ca2+]i was exclusively localized to the cytoplasm, particularly in the branching processes. Increases in [Ca2+]i more than four-fold were associated with a simultaneous and transient reduction of cell area indicating reversible cell contraction. Our results indicate that the Ca(2+)-dependent contraction of human FSC in vitro may reflect a potential role in regulating sinusoidal blood flow in vivo.

Angiotensin II↗
PubMed1992

[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study].

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.

Adult↗
PubMed1991

Cell kinetics and hormonal features in relation to pathological stage in breast cancer.

Proliferative activity (expressed as 3H-thymidine labeling index, 3H-TdR LI) was evaluated on a series of 281 primary tumors recruited in two years in 6 different institutions from central Italy. 3H-TdR LI proved to be low in intraductal, or well and moderately differentiated, or hormone receptor positive tumors. Conversely, no relation was observed between 3H-TdR LI and menopause, tumor size, or lymph node involvement. An inverse relation was observed between 3H-TdR LI and hormone receptor content. Specific patterns of 3H-TdR LI value and ER content association were observed as a function of menopause, lymph nodal status, and degree of lymph nodal involvement.

Breast Neoplasms↗
PubMed1991

Evidence for alpha 1-adrenoreceptor hyperresponsiveness in hypotensive cirrhotic patients with ascites.

Cirrhosis with ascites is often characterized by arterial hypotension associated with increased plasma norepinephrine levels. Clinical evidence suggests a decreased sensitivity to norepinephrine in this clinical setting, indicating a potential derangement of alpha 1 adrenoreceptors. The aim of the present study was to evaluate the reactivity of the alpha 1-adrenoreceptor, using phenylephrine, a selective alpha 1 receptor agonist. First, we evaluated the pupillar response to the intraconjunctival administration of the agonist. Hypotensive cirrhotic patients showed a trend to a more marked and prolonged response, compared with age-matched healthy controls. Second, we studied the response of alpha 1-adrenoreceptors in the peripheral vasculature by administering iv phenylephrine to a similar group of patients. A significantly greater and longer lasting pressor response was observed in hypotensive cirrhotic patients (p less than 0.0001 vs. healthy controls). Our results indicate that in this group of patients, there is a rather peculiar situation, characterized by alpha 1-adrenoreceptor hyperresponsiveness in the presence of high levels of circulating norepinephrine. This finding could be related to biochemical abnormalities within the peripheral sympathetic nervous system endings.

Adult↗
PubMed1991

Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study.

In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗
PubMed1990

In vivo manipulation of human breast cancer growth by estrogens and growth hormone: kinetic and clinical results.

Since 1983, a series of experimental and clinical studies have been carried out on the possibility of enhancing the chemotherapy effectiveness in breast cancer by expanding the fraction of cycling cells. Theoretically estrogens should recruit breast cancer cells and this fact should result in a higher killing efficiency of antiproliferative drugs. Actually it has been clearly shown, by means of the thymidine labeling index and primer-dependent alpha-DNA polymerase assay, that low doses of diethylstilbesterol are able to increase the tumor proliferative activity of human breast cancer in vivo (estrogenic recruitment). Three randomized trials have been carried out (one in locally advanced and two in metastatic breast cancer) comparing conventional polychemotherapy vs chemotherapy with estrogenic recruitment. Only limited advantages have been observed in these trials. Searching for new modalities of kinetic manipulation of tumors, recombinant human growth hormone has been employed in a pilot study: the preliminary results indicate that it largely enhances tumor proliferative activity, suggesting the possibility of employing a growth factor system to increase chemosensitivity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1977

[Dynamic BSP tests in cholelithiasis patients before and during chenodeoxycholic acid therapy; initial results].

The BSP loading and continuous infusion tests were performed in 7 patients before and after a two-week treatment with chenodeoxycholic acid (10 mg/Kg/die per os). The following parameters were evaluated: 45th minute retention percentage, plasma disappearance rate during the first 16 minutes, compartmental transfer rates, transport maximum and storage. Our results indicated that no cholestatic effects seemed to be induced during the first period of treatment with chenodeoxycholic acid.

Adult↗