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Biomedical subjects

G Gentili

Publications and source records attributed to G Gentili.

At least 37 records · Page 2Linked to original sources

Risk of human immunodeficiency virus infection and genital ulcer disease among persons attending a sexually transmitted disease clinic in Italy.

To assess the relative importance of ulcerative and non-ulcerative sexually transmitted disease in the transmission of HIV, a seroprevalence study was conducted on 2210 patients at the sexually transmitted diseases (STD) clinic of the S. Maria e S. Gallicano Hospital in Rome, between 1989 and 1994. Among male patients, by univariate analysis, strong predictors of HIV infection were homosexuality, sexual exposure to a HIV-positive partner, hepatitis B virus infection, and positive syphilis serology. An increased risk was estimated for patients with past genital herpes (odds ratio (OR) 3.86, 95% confidence intervals (CI) 0.40-18.2), and primary syphilis (OR 5.79, 95% CI 0.59-28.6). By multivariate analysis, a positive association was found with homosexuality (OR 6.9, 95% CI 2.9-16.5), and positive syphilis serology (OR 3.5, 95% CI 1.3-9.2). An adjusted OR of 2.41 was calculated for current and/or past genital herpes. These results, although not conclusive, suggest a role of ulcerative diseases as risk factors for prevalent HIV infection, and indicate that positive syphilis serology is an unbiased criterion for identifying individuals at increased risk of HIV infection.

Adult↗

5-ASA-glutamate protects rats from inflammatory bowel disease induced by intracolonic administration of trinitrobenzensulfonic acid.

BACKGROUND AND AIMS: A new amino acid derivative of 5-aminosalicylic acid, 5-ASA-glutamate, releases 5-aminosalicylic acid independently of the action of bacterial azoreductases or adapt intestinal pH. In this study, 5-ASA-glutamate was compared with sulphasalazine with respect to: 1) therapeutic action, 2) effects on the synthesis of eicosanoids, 3) regional release of 5-aminosalicylic acid in the intestine. METHODS: Colitis was induced in 29 rats by intracolonic administration of trinitrobenzensulfonic acid. Nine animals received an equal amount of saline. Three days after induction of colitis, animals were randomly assigned to equimolecular doses of 5-aminosalicylic acid as sulphasalazine (1040 mg/kg bw day) or 5-ASA-glutamate (850 mg/kg bw day) or arabic gum in water, given intragastrically. Arabic gum was also administered to animals that had received a saline enema (control group). The guts of 3 rats from the 5-ASA-glutamate group and 3 from the sulphasalazine group were used to assess regional release of 5-ASA, while in all the others, after 21 days of treatment, macroscopic and histologic lesions were assessed and eicosanoids and leukotriene determinations were performed. RESULTS: The 5-ASA-glutamate group had macroscopic (2.20 +/- 0.58) and histologic (2.80 +/- 1.24) significantly lower scores than the trinitrobenzensulfonic acid group (3.40 +/- 0.22 and 6.50 +/- 1.2 respectively). 5-ASA-glutamate group had reduced PGE2 (-31%) and TXB2 (-25%) more effectively than the sulphasalazine group. LTB4 release was not affected by 5-ASA-glutamate treatment, while sulphasalazine produced a non significant, but quite consistent, reduction in LTB4 release (-37%). The release of 5-ASA after sulphasalazine was higher in the small intestine, lower in the colon compared to that following 5-ASA-glutamate administration. CONCLUSIONS: 5ASA-glutamate was effective in reducing the macroscopic and histologic score in the trinitrobenzensulfonic acid induced colitis. It also had some effect in reducing eicosanoid synthesis and could be a promising drug for the treatment of inflammatory bowel disease.

Animals↗

Local and systemic effects of intraduodenal exposure to topical gallstone solvents ethyl propionate and methyl tert-butyl ether in the rabbit.

During topical dissolution of gallstones, solvent can escape to the duodenum causing toxic effects that have not yet been adequately quantified. We compared the local intestinal cytotoxic and systemic hepatotoxic effects of two gallstone solvents, methyl tert-butyl ether and ethyl propionate, on the rabbit's duodenum. Methyl tert-butyl ether, ethyl propionate, or saline (control) was infused intraduodenally for 3 hr in 32 male New Zealand rabbits. The solvents were infused either at a high infusion rate of 8.5 microl/min or at a low rate of 4.0 microl/min. Blood samples were collected for biochemical analysis from each animal before and after the 3-hr infusion period. A standardized histologic scoring system was used by a pathologist blinded to the treatments to quantify liver and intestinal tissue injury. None of the animals studied showed any significant changes in serum alkaline phosphatase, amylase, bilirubin, or their hepatic histology or histologic scoring for mucosal necrosis and ulceration. At the higher dose, methyl tert-butyl ether produced significantly more submucosal inflammation (P = 0.0017) and showed a trend of causing more submucosal edema than ethyl propionate, but ethyl propionate led to significantly higher elevations of aminotransferases than methyl tert-butyl ether as compared to saline. There were no detectable blood levels of methanol or ethanol in any of the animals studied. Ethyl propionate may be less damaging to the intestinal mucosa of the rabbit than methyl tert-butyl ether, but at the higher dose (equivalent to 60 ml/3 hr in a 70-kg human) it appears to produce more biochemical liver injury when administered intraduodenally.

Administration, Topical↗

Incidence and determinants of hepatitis C virus infection among individuals at risk of sexually transmitted diseases attending a human immunodeficiency virus type 1 testing program.

BACKGROUND: The role of sexual transmission of hepatitis C virus (HCV) infection is still not completely understood, partly because of the lack of longitudinal studies among cohorts of HCV-negative individuals who engage in at-risk sexual behavior. GOALS: To evaluate the incidence of HCV infection in a population at risk for human immunodeficiency virus type 1 (HIV-1) infection and other sexually transmitted diseases (STD) and to identify factors associated with HCV seroconversion. STUDY DESIGN: A retrospective longitudinal study was carried out on a cohort of consecutive attendees of a voluntary HIV-1 testing and counseling program in a large STD center in Rome. All individuals undergoing at least two consecutive tests for HCV antibodies were enrolled. Clinical data and information on individual behavior were collected for all study participants. RESULTS: Between June, 1992 and December, 1994, a total of 709 individuals (12 intravenous drug users [IDU], 244 homosexuals, and 453 heterosexual non-IDUs), initially negative for HCV antibody, were tested more than once. Among these individuals, 15 HCV seroconversions occurred. The average follow-up time was 1.25 person/years (p/y) for an incidence rate of 1.69 per 100 p/y. The incidence rates by exposure category were 39.30 per 100 p/y among IDUs, 1.37 per 100 p/y among homosexual men, and 0.97 per 100 p/y among heterosexual non-IDUs. Excluding IDUs, of the 697 STD clinic attendees engaging in at-risk sexual behavior, HIV-1-positive status tended to be associated with HCV seroconversion (relative hazard = 5.48; 95% confidence interval = 0.85-35.40). The HCV crude incidence rates among HIV-1-infected patients at enrollment was 11.5%, 4.2%, and 2.4% in those with severe, moderate, and mild levels of immunosuppression, respectively (chi-square for trend = 2.38, P = 0.1). CONCLUSIONS: In this cohort, HCV infection was confirmed to be strongly associated with intravenous drug use. Nonetheless, the occurrence of two thirds of the total HCV seroconversions in non-IDU individuals engaging in at-risk behavior suggests a role of sexual practices in the transmission of the infection. Among non-IDU individuals, the risk for development of HCV infection tended to increase in those who were HIV-1 infected.

Adolescent↗

Interferon plus ursodeoxycholic acid versus interferon in the treatment of chronic C viral hepatitis.

BACKGROUND: The aim of as study was to ascertain whether the association of interferon alpha-2a and ursodeoxycholic acid (IFN+UDCA) was more efficacious in ameliorating liver parameters than interferon (IFN) alone in patients with chronic hepatitis C. METHODS: Forty-one chronic hepatitis C patients, who had at least twice the normal value of one transaminase, were randomly assigned to treatment with IFN + UDCA (n = 21) or IFN alone (n = 20). IFN was administered subcutaneously at a dose of 3 MU thrice weekly, UDCA orally at 10 mg/kg bw/day. IFN therapy was terminated 6 months later and the responders (normalized transaminases) of both groups were treated with UDCA alone for a further 12 months. RESULTS: In the IFN + UDCA group there were 2 drop-outs from therapy and 11 responders, while in the IFN group they were, respectively, 3 and 10. Transaminases normalized after the first month of treatment in 7/11 responders with IFN + UDCA compared with 3/10 in the IFN responders group. The trend to normalization was more rapid with IFN + UDCA than with IFN alone (chi 2t = 3.95; p < 0.05). Disease relapse (defined as at least one transaminase > x 1.5 the normal value) was 3/11 in the IFN + UDCA group and 4/10 in the IFN group. 2/11 responders in the IFN + UDCA and 1/10 in the IFN group were HCV RNA negative by PCR. The total Knodell histological score decreased more in the IFN+UDCA than in the IFN group (-2.67 +/- 3.44. vs -1.67 +/- 2.16, mean +/- SD). CONCLUSIONS: The administration of UDCA determine an earlier normalization-time of transaminases in the patients responders to IFN therapy and could be useful to reduce the relapse into disease after the IFN therapy.

Adolescent↗

Risk factors for hepatitis B virus infection among homosexual men attending a sexually transmitted diseases clinic in Italy.

Prevalence of and risk factors for hepatitis B virus (HBV) infection were determined among 252 homosexual men with no history of intravenous drug use (median age 33 years, range 18-77) treated at a sexually transmitted disease (STD) clinic in Rome. The overall prevalence of antibodies to HBV core antigen (anti-HBc) was 50.8%, a rate nearly nine times as high as the 5.8% found recently in a national sample of young male adults, aged 18-26 years, and twice as high as the 22% found in heterosexuals attending the same clinic over the same period of time. Multiple logistic regression analysis showed that the risk of anti-HBc positivity was independently associated with increasing age, five or more sexual partners in the previous year, positive HIV serology and positive syphilis serology. Lower level of schooling, lack of condom use, history of non-ulcerative STD, current or past history of genital herpes, and positive anti-HCV serology were not associated with anti-HBc positivity. These findings corroborate the importance of sexual transmission of HBV in homosexual men. Behavioural factors, such as multiple sexual partners, probably enhance the efficiency of this mode of HBV transmission.

Adolescent↗

Risk factors for hepatitis B virus infection among heterosexuals attending a sexually transmitted diseases clinic in Italy: role of genital ulcerative diseases.

The seroprevalence and risk factors for hepatitis B virus (HBV) infection were determined among 1,497 heterosexuals with no history of intravenous drug use (median age 32, range 15-78) treated at a sexually transmitted disease clinic in Rome. A total of 329 (22.0%) had antibodies to HBV core antigen (anti-HBc), a rate nearly four times as high as the 5.8% found recently in a national sample of young male adults, ages 18-26 years. Multiple logistic regression analysis showed that the risk of anti-HBc positivity was independently associated with male sex, increasing age, lower level of education, three or more sexual partners in the previous year, and positive syphilis serology. Lack of condom use, history of nonulcerative sexually transmitted diseases, and genital herpes were not associated with anti-HBc positivity. These findings confirm that heterosexual exposure plays an important role in the spread of HBV infection. Furthermore, these data indicate that individuals with more than two sexual partners a year and those with positive syphilis serology should be immunised against HBV.

Adolescent↗

Effect of ursodeoxycholic acid on hypertransaminasaemia and bile acid composition in patients undergoing bone marrow transplantation--a double-blind randomized control study.

A double-blind randomized placebo controlled trial of ursodeoxycholic acid was performed in 31 patients undergoing T-cell depleted allogeneic or autologous bone marrow transplantation to determine the effectiveness of this hydrophilic bile acid in improving the increase in serum liver enzymes that generally accompanies this procedure. Neither group showed any significant difference in magnitude of the increases in serum transaminases and gamma-glutamyltranspeptidase following the conditioning regimen that included chemotherapy and total body irradiation. In the 6 months after transplantation, serum enzymes decreased in both groups, but were consistently higher in the placebo treated patients, indicating that ursodeoxycholic enhances normalization of liver. Faecal bile acid showed that following chemotherapy and irradiation in which intestinal bacteria are ablated, secondary bile acid formation was practically abolished and faeces contained mainly cholic and chenodeoxycholic acids. During bile acid treatment, ursodeoxycholic acid accounted for 31.3 +/- 10.9% of faecal bile acids compared with 4.0 +/- 2.1% in the basal period. Serum and urinary ursodeoxycholic acid concentrations (mean +/- SD, 13.3 +/- 6.9 mumol/L and 2.65 +/- 0.84 mumol/L, respectively) were significantly higher in patients receiving bile acid than in thos on placebo (mean +/- SD, 0.15 +/- 0.12 mumol/L and 0.29 +/- 0.35 mumol/L, respectively) thus confirming compliance.

Administration, Oral↗

Immunity to diphtheria in the 4-70 year age group in Italy.

Diphtheria antibody level in serum samples obtained from 270 subjects aged 4-70 was measured by in vitro seroneutralization test on Vero cells. Of the studied population, 27.8% had an antibody titre below the protective level (< 0.01 IU/ml). The prevalence of susceptible subjects showed a significant age-related increase (p < 0.01), with the highest value (53.8%) in the 31-40 age group. Mean antibody titre was maximum in individuals aged 13-14, then decreased reaching the minimum level in the 41-50 age group. These data suggest that in individuals aged 30-50, diphtheria immunity is not satisfactory, both for prevalence of immune subjects and for antibody levels. Therefore, a revaccination of adults with reduced doses of diphtheria toxoid may be advisable.

Adolescent↗

Cognitive event-related potential in hepatic encephalopathy.

A study of auditory P300 was performed on 24 patients with cirrhosis of the liver: 13 patients with hepatic encephalopathy (HE grade 1-2) and 11 patients without clinical encephalopathy (HE grade 0). The patients were also assessed using spontaneous EEG and neuropsychological methods: Mini Mental State, Digit Span and Number Connection Test. The P3 latency was found to be significantly increased in all patients (100%) with HE grade 1-2 and in 6 patients (54.5%) with HE grade 0. The clinical value of using the P300 latency in the hepatic encephalopathy is subsequently discussed.

Aged↗

Detection of anti-HCV antibodies in immunoglobulin preparations by recombinant immunoblot assay.

The presence of anti-HCV antibodies in immunoglobulin preparations was investigated by recombinant immunoblot assay (RIBA) and enzyme immunoassay (EIA). While EIA was found to be suitable for detecting anti-HCV antibodies in immunoglobulin preparations, the RIBA could not be used without modifying the standard procedure developed for use with human sera. The two modifications were: (1) incubation with the anti-human IgG conjugate in a single test tube for each strip, instead of in a common vessel; (2) removal of the conjugate after 15 min and its replacement with fresh conjugate for a second 15 min incubation period. Thirty-six immunoglobulin preparations were tested using this modified procedure. Twenty-nine out of 31 (93.5%) preparations received in 1992 were anti-HCV positive, whereas the five immunoglobulin preparations received in 1993 were negative. These results were compared with those obtained on the same samples with the EIA. The percentage of samples positive with EIA was 74.2%. The difference between the results obtained with modified RIBA and EIA was statistically significant (P < 0.05).

Hepatitis Antibodies↗

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Aminopeptidases↗