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Biomedical subjects

P Andreone

Publications and source records attributed to P Andreone.

71 records · Page 4Linked to original sources

[Relation between acute changes in diuresis and renal prostaglandins. I: Induced hypotonic polyuria].

We have evaluated the effects of indomethacin (I) and of a rich in linoleic acid phosphatidylcholine (E) on the renal function and on the PGE urinary excretion during steady hypotonic polyuria. 5 normal subjects have been studied in the absence of treatment (TA) and after treatment with I, E, E + I. The renal function has been estimated by clearance (cl.) method during hypotonic polyuria induced by oral water loading and i.v. infusion of 5% dextrose solution. The glomerular filtration rate has been estimated by cl. of endogenous creatinine; moreover have been measured the osmotic clearances (Cosm, CH2O), the sodium and potassium clearances (CNa, CK), the mean arterial pressure (PA) and the urinary prostaglandins of E series (PGE) by RIA method. In I condition is observed: a) a trend to a glomerular filtration rate decrement; b) a significant decline of the urinary flow rate, CH2O, UPGV and a significant increment of the urinary osmolarity; c) a trend to an increment of potassium and a decrement of sodium urinary excretions; d) a significant increase of PA. It is possible that the contrary effects observed during the hypotonic polyuria in E condition depend on the stimulating effects of this material on the PG intrarenal synthesis.

Adult↗

[Relation between acute changes in diuresis and renal prostaglandins. II. Induced antidiuresis].

We have evaluated the effects of indomethacin (I) and of a rich in linoleic acid phosphatidylcholine (E) on the renal function during in bolo infusion of lysine-8-vasopressin (LVP). 5 normal subjects have been studied in the absence of treatment (TA) and after treatment with I, E, E+I respectively. Two clearance (cl.) periods have been performed in the following time intervals: 0-30 min and 30-60 min after in bolo LVP (1.5 m-U.kg-1) infusion. Have been measured: the urinary flow rate, V, the endogenous creatinine cl., Cc, the osmotic clearances, Cosm, CH2O, the sodium and potassium cl., CNa, CK, the urinary prostaglandins (PG) of E series excretion (UPGV) by RIA method and the mean of arterial pressure (PA). 1) In TA condition LVP decreases V, Cosm, Cc, CH2O, CNa, CK and slightly increases the urinary osmolarity; these effects regress during the interval 30-60 min. 2) In I condition LVP produces a significant increment of PA and prolonged and intensified decrement of Cc, CH2O, V; in this condition the increase of urinary osmolarity is greater than in TA condition. 3) The E-treatment alone does not affect the LVP-induced renal effects; however the enhancement of these effects produced by I is attenuated in the presence of E though UPGV does not differ in I and E+I.

Creatinine↗

[Sulpiride (stereoisomers, racemic) and dopamine: actions and interactions on renal circulation].

Interaction of sulpiride - both 1- and d- isomers as well as racemic- - with Dopamine (DA, subpressor dosage 0.1 microgram X kg -1 X min -1), on the renal hemodynamic, was studied in DOCA-pretreated men during hypotonic polyuria. P.A.H. and creatinine clearance and renal vascular resistances were determined. In the presence of d-Sulpiride, DA - induced renal vasodilation is carried out gradually and finally reaches similar levels as in the absence of d-Sulpiride. However no glomerular filtration rate increase is produced by DA. In the presence of 1-Sulpiride, DA vasodilating effect is suppressed. On the contrary a trend toward ischemia and a reduction in glomerular filtration rate becomes finally apparent. Stronger binding of 1- than d-Sulpiride with vascular DA receptors in suggested. When both isomers are simultaneously administered (at the nearly total dosage) much less inhibitory effect on DA vasodilator action is observed: it seems that each isomer decreases the affinity on the other isomer for vascular DA receptors.

Desoxycorticosterone↗

[Sulpiride (stereoisomers, racemic) and dopamine: actions and interactions on tubular reabsorption].

In DOCA-pretreated men during hypotonic polyuria Dopamine (DA) infusion in a subpressor dosage (0.1 microgram X kg -1 X min -1) produces renal hyperemia, inhibition of isosmotic sodium reabsorption, increase in sodium distal load (s. d.l.) and finally inhibition of anisosmotic sodium reabsorption as a percentage of s.d.l. Such DA effects are variously modified by sulpiride isomers. Sodium distal load increase is still apparent in the presence of racemic, but not in the presence of either d- or l-Sulpiride isomers. However DA inhibition of anisosmotic sodium reabsorption % s.d.l. is unaffected by either or both Sulpiride isomers. If the DA tubular inhibition was dependent on specific DA receptors these receptors, unlike vascular DA receptors, would bind in a weaker way both d- and l-Sulpiride isomers.

Absorption↗

[Sulpiride (stereoisomers, racemic) and dopamine: actions and interactions on renal excretion of hydro-saline].

Renal effects of Dopamine (DA, subpressor dosage 0.1 microgram X kg -1 X min -1) during hypotonic polyuria in moderate hydro-saline retention are variously modified by either d- or l-Sulpiride isomers. In the presence of d-Sulpiride, DA effects, such as an increase in diuresis, free water clearance (CH20) and kaliuresis are suppressed, while increases of saluresis and natriuresis are significantly blunted. In the presence of l-Sulpiride no changes are observed in both saluresis and natriuresis, while decreases occur in diuresis, CH20 and kaliuresis. The inhibitory DA effects on isosmotic sodium reabsorption as a percentage of sodium filtered load are prevented by either isomer as well. A possible role of ineffective renal vascular DA action can be involved in such defective tubular inhibition. However is also suggested a pharmacological blockade of proximal tubular specific DA receptors.

Body Water↗

[Catecholamine receptors and renal function].

Renal function was assessed through clearance studies in man under initial conditions marked by retention (23 experiments) and hydro-saline depletion (19 experiments). Further evaluations were carried out in depletion combined with treatment with (+/-)-propranolol (9 experiments) or with prazosin (9 experiments). In each study, clearance was checked during and after venous infusion of 0.1 micrograms/kg-1/min-1 DA, in addition to the control clearance. Adrenolytic drugs and renal function in hydro-saline depletion. Combination with propranolol had no significant effect on renal function, whereas prazosin led to a significant increase in both total and afferent renal vascular resistance; the flow rate and filtrate were less despite higher arterial pressure. Both the absolute and the percentage loading value of isosmotic and anisosmotic sodium reabsorption were inhibited. Renal action of DA in depletion with and without adrenolytic drugs. DA failed to produce either vasodilatation or a hydro-natriuretic effect during hydro-saline depletion, by contrast with its effect at the same dose during retention. During its infusion, however, it led to sodium saving dependent on stimulation of distal sodium reabsorption; following suspension, this saving increased still further, and there was a significant decrease in flow rate, filtrate and diuresis. Pretreatment with either drug restored the vasodilatatory and hydrosaluretic capacity of DA. Modalities whereby renal function is controlled in the presence of changes in body water and salt content. 1) During retention and during depletion in association with prazosin, anisosmotic transport of sodium is efficient in inverse proportion to the sodium load reaching the diluting segments. Prazosin depresses reabsorption efficiency in the presence of load values similar to those observed during simple depletion. 2) During retention, urinary sodium naturally depends on plasma osmolarity, whereas blood sodium appears to depend on urinary excretion of sodium. During depletion, renal excretion apparently depends on mean blood pressure. These extra-renal control mechanisms probably result in alteration of one or more of the components of the direct line running from the filtrate to the formation urine. 3) When DA is infused during water-salt retention, renal excretory function can be seen to depend on the glomerular filtrate through direct control of diuresis. During depletion in the early stage of DA infusion, on the other hand, the filtrate depends on excretory function through tubulo glomerular feedback control.

Adult↗

[Effects of acute changes in water balance on hydrosaluresis and on urinary excretion of prostaglandin E, in the presence and absence of a cyclooxygenase inhibitor].

Five healthy females were studied in order to evaluate the effects of a cyclo-oxygenase inhibitor agent (Indomethacin, I) on the hydro-saluresis and urinary excretion of prostaglandins (PG) of E series. Each subject was studied during both hypotonic polyuria (oral water load) and hypertonic olyguria (18 h water intake withheld). 1) In water diuresis I. treatment significantly (P less than 0.05) decreased urinary flow (36%) as well as sodium and potassium excretions (32%, 46%, respectively); the rise in urinary osmolarity (86%) and the fall in PGE excretion (63%) were statistically insignificant. 2) In antidiuresis I. treatment significantly (P less than 0.05) decreased urinary flow (50%) as well as sodium, potassium and PGE excretions (55%, 45%, 85%, respectively); furthermore urinary osmolarity was increased (26%, P less than 0.01). If I. renal effects are mediated by PG biosynthesis inhibition, the above data are consistent with an involvement of PG in hydrosaluresis control (at least in our experimental conditions).

Diuresis↗

Clinical significance of antibodies to polymerized human albumin detected by enzyme-linked immunosorbent assay.

Antibodies directed against glutaraldehyde-polymerized human serum albumin (pHSA) were tested by a sensitive and specific enzyme-linked immunosorbent assay (ELISA) in serum samples from 196 patients with various hepatic and non-hepatic diseases and in 38 healthy control subjects. A very high prevalence (80.1%) of antibody response was found in the patient group, ranging from 60% in type non-A, non-B (NANB) chronic active hepatitis (CAH) and lymphomas to 95.5% in hemodialysis patients. A higher prevalence of anti-pHSA antibodies was found in hepatitis B virus (HBV)-related CAH and hemodialysis patients compared with NANB-related CAH, collagen diseases and lymphomas. Anti-pHSA antibodies were most frequent in HBsAg-positive cases, but no correlation between antibody response and the HBeAg/anti-HBe status was found among these patients. Anti-pHSA antibodies did not correlate with HBsAg-associated pHSA receptors determined by radioimmunoassay (RIA). Moreover, a significantly higher pHSA receptor expression was found in HBV-related CAH and hemodialysis patients compared with chronic HBsAg carriers and in HBeAg-positive patients compared with HBeAg-negative cases. The anti-pHSA response seems to be related to the presence of immunoregulation disorders which may be induced by several causes, such as autoimmunity and viral infections. In particular, as far as the HBV infection is concerned, there is no evidence that circulating anti-pHSA antibodies interfere with the natural course of the disease.

Autoantibodies↗

Role of prostaglandin E2 on defective interferon-gamma production during type B acute viral hepatitis.

Interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) production was evaluated in cultured peripheral blood mononuclear cells taken from patients with type B acute viral hepatitis at the onset of symptoms, at 1st and 2nd week of disease, and from healthy controls. Concanavalin A-stimulated cells cultured for 24, 48 and 72h showed significantly higher IFN-gamma levels compared to basal release in both groups, whereas no statistically significant differences were found in most experimental conditions as regard PGE2 synthesis. No differences were found in IFN-gamma production by comparing patients with acute viral hepatitis to the control group, whereas PGE2 was significantly increased during the disease. IFN-gamma and PGE2 levels did not show any significant change in acute viral hepatitis during the follow-up. A statistically significant correlation was found only in control group between IFN-gamma and PGE2 levels in unstimulated cultures. PGE2 seems to play a central role in regulating interferon production during viral infection. This may suggest a new therapeutic approach in viral hepatitis utilizing a combination of interferon and prostanoid inhibitory substances, above all in patients who do not respond to interferon therapy alone.

Acute Disease↗

Genetic heterogeneity of hepatitis C virus (HCV) in clinical strains of HIV positive and HIV negative patients chronically infected with HCV genotype 3a.

The clinical correlation between the degree of HCV variability and the response to anti-HCV treatment in HIV positive patients infected with HCV genotype 3a is unknown. In this study, 27 HIV positive and 5 HIV negative patients with HCV genotype 3a infection were treated with interferon-alpha-2b with or without ribavirin. Nine patients (5 HIV positive) achieved a sustained virological response (SR) and 23 (only one HIV negative) were non-responders (NR). Sequence analyses of the partial E2 domain and the non-structural 5A protein were performed at baseline in all patients, and before and during treatment in the HIV positive NRs. There was no difference in the mean number of amino acid mutations from HCV 3a prototype, within E2 region, between the HIV positive and HIV negative patients: 17 (range 11-25) vs 16 (range 14-17). The mean baseline number of mutations in E2 region, was similar in HIV positive SRs and NRs: 18 (range 14-25) vs 16 (range 11-19). Phylogenetic analysis of HCV paired serum samples at baseline and during treatment revealed identical E2 sequence in 5/21 HIV positive NR patients, whereas 6 other sequences were strictly related to baseline E2 domain and the remaining 10 were divergent. The mean number of amino acid mutations in the NS5A protein at baseline, was 1 (range 0-3) in HIV negative patients and 2 (range 0-4) in HIV positive ones. This region was highly conserved in all isolates of HIV positive NRs analysed during treatment. These results suggest that genetic variability at baseline within the E2 region and NS5A protein of HCV 3a strain obtained from HIV positive and HIV negative patients is not associated with treatment response. Furthermore, the anti-HCV treatment did not influence HCV heterogeneity within the E2 and NS5A domains in HIV positive patients infected with HCV genotype 3a.

Adult↗

Sequence analysis of NS3 protease gene in clinical strains of hepatitis C virus.

The amino terminal region of the non structural gene 3 (NS3) of hepatitis C virus (HCV) is a chymotripsinlike serine-protease responsible for cleavage of the non structural proteins of Hepatitis C virus (HCV). In order to investigate the genetic variation of this region, we developed a nested PCR to obtain NS3 protease sequences from 54 patients chronically infected with HCV genotypes 1a, 1b and 3, respectively. Comparison of nucleotide and amino acids sequences of NS3 protease domain with consensus sequence obtained within the same genotype, showed 3.73% nucleotide divergence and 1.64% amino acid divergence in isolates of genotype 3a, whereas isolates 1a exhibited 4.45% nucleotide and 4% amino acid change, respectively. Finally, NS3 sequence from 1b isolates revealed 6.47% nucleotide and 3.5 % aa changes. Comparison of consensus amino acid sequences derived from isolates 1a, 1b and 3, with the HCV prototypes showed a low amino acid sequence diversity. However, the consensus sequence of HCV genotype 3 isolates showed an amino acid changed from the prototype, that was located within a region important for enzyme structure and activity. These results indicated that the NS3 protease gene is highly conserved within the same HCV genotype. The domains involved in enzyme function were highly conserved in 1a and 1b strains, whereas consensus sequence of isolates 3a showed that the majority of these strains were not perfectly conserved in one of such regions. These findings altogether suggested that the NS3 protease enzyme of HCV may constitute an important target for antiviral therapy, but the NS3 protease variability of isolates 3 within a region that is a potential target for antiviral therapy could pose a problem for structure based drug development.

Adult↗

Prostanoids in peritoneal fluid of infertile women with pelvic endometriosis and PID.

Peritoneal fluid collected at celioscopy in infertile subjects was assayed for steroids and several prostanoids (PGE2, PGF2, TXB2, LTB4) as part of a study into pathophysiology of the female reproductive tract. Prostaglandins, produced massively in the pelvis, might interfere with fertility through various mechanisms (alterations in the egg implantation, follicle genesis, luteinization as well as tubal disorders). Our study of 54 patients showed a marked increase only of TXB2 out of the prostanoids assayed in overall endometriosis. In pelvic flogosis peritoneal LTB4 (and TXB2) were considerably increased if related to controls. This would suggest their role in the ethiopathogenesis of unexplained infertility (in relation to these pathologic patterns).

Ascitic Fluid↗