Biomedical subjects

A L Martinelli

Publications and source records attributed to A L Martinelli.

12 recordsLinked to original sources

PubMed2000

Porphyria cutanea tarda in Brazilian patients: association with hemochromatosis C282Y mutation and hepatitis C virus infection.

OBJECTIVE: Porphyria cutanea tarda (PCT) is commonly associated with iron overload and hepatitis C virus (HCV) infection. Association between hemochromatosis C282Y or H63D mutations and PCT has been observed, although not uniformly, and iron overload is also commonly found in chronic HCV hepatitis. The aim of the present study was to investigate the frequency of C282Y and H63D mutations and HCV infection in Brazilian patients with PCT and their relationship with iron overload. METHODS: Twenty-three patients (19 men) aged 39.6 +/- 11.1 yr were studied. All had dermatological lesions of PCT and high levels of urinary uroporphyrin. HCV infection and iron overload were investigated. DNA samples were analyzed for the presence of HFE mutations. RESULTS: The frequency of C282Y was significantly higher in PCT patients than in 278 healthy individuals (17.4% vs 4%, odds ratio = 5.1, 95% confidence interval 1.5-17.6, p = 0.02), whereas no difference was observed regarding the H63D mutation (30.4% vs 31%, odds ratio = 1, 95% confidence interval 0.4-2.4, p = 1). Biochemical tests in PCT patients showed iron overload with transferrin saturation = 47.3 +/- 20.7% and ferritin = 566.8 +/- 425 ng/ml. Fifteen of 23 (65.2%) patients had HCV infection and alcohol ingestion was observed in 17 of 23 (73.9%). CONCLUSIONS: PCT patients exhibited evidence of iron overload, a high frequency of HCV, and an association with C282Y mutation. These data further support the notion that both acquired and inherited factors contribute to the occurrence of PCT, and indicate that screening for C282Y may be justified in PCT patients.

Adult↗

PubMed2000

Are haemochromatosis mutations related to the severity of liver disease in hepatitis C virus infection?

It has been proposed that iron overload may adversely affect liver disease outcome. The recent identification of 2 mutations in the HFE gene related to hereditary haemochromatosis (Cys282Tyr and His63Asp) provided an opportunity to test whether they are associated with hepatic iron accumulation and the activity and severity of liver disease in hepatitis C virus (HCV) infection. We investigated the prevalence of HFE mutations in 135 male patients with chronic HCV hepatitis, and correlated genotype distribution with different parameters of iron status and the activity and severity of liver disease. Of these 135 patients, 6 (4.4%) carried Cys282Tyr and 32 (23.7%) carried His63Asp, frequencies which were similar to those observed in healthy controls. Serum iron levels and transferrin saturation (but not ferritin levels or liver iron content) were significantly higher in carriers than in non-carriers of HFE mutations. No difference was observed in serum ALT, AST and GGT levels between carriers and non-carriers. Finally, scores for necroinflammatory activity and fibrosis in the liver were significantly higher in HFE carriers than in non-carriers. Patients with chronic HCV infection carrying HFE mutations tend to present more evident body iron accumulation and a higher degree of necroinflammatory activity and fibrosis in the liver. HFE gene mutations might be an additional factor to be considered among those implicated in the determination of a worse prognosis of the liver disease in chronic HCV infection.

Adolescent↗

PubMed1999

Abnormal uroporphyrin levels in chronic hepatitis C virus infection.

A strong association between hepatitis C virus (HCV) infection and porphyria cutanea tarda (PCT) has been observed, but the implications of the viral infection in the metabolism of porphyrins in patients without clinical manifestations of PCT are not known. The levels of porphyrin in plasma and uroporphyrin (URO) and coproporphyrin (COPRO) in 24-hour urine were measured in 156 patients with chronic HCV infection showing no clinical evidence of PCT. Levels of URO higher than the upper limit were observed in 35 of 156 patients (22.4%). The range and the mean values +/- standard deviation were 26-1,196 microg/24 hours and 82 +/- 204 microg/24 hours. Increased levels of COPRO and plasma porphyrin were observed in 12 of 156 patients (7.7%) and 2 of 156 patients (1.3%) respectively. There were no differences between patients with increased URO levels and patients with normal URO levels in terms of gender, age, risk factors for HCV infection, alcohol abuse, or hepatitis B viral infection. Transferrin saturation (p = 0.040), gamma glutamyl transpeptidase (p < 0.0001), aspartate aminotransferase (p = 0.006), and alanine aminotransferase (p = 0.040) were significantly higher in patients with abnormal URO than in patients with normal URO. The frequency of cirrhosis was higher, but not significantly different, in patients with increased URO (16.7%) compared with patients with normal URO (3.8%). The authors demonstrated that even without a clinical manifestation of PCT it is possible to detect abnormalities in the metabolism of porphyrins in patients with chronic HCV infection. The implications of these findings deserve additional investigation.

Adolescent↗

PubMed1996

Quantitative assessment of hepatitis C virus RNA and IgM antibodies to hepatitis C core in chronic hepatitis C.

BACKGROUND/AIMS: IgM antibodies to hepatitis C virus have been found in a variable proportion of patients with chronic hepatitis C. We have evaluated whether IgM anti-core antibodies correlate with viraemia or hepatic injury in chronic hepatitis C. METHODS: Serum from 106 patients with chronic hepatitis C with varying stages of disease were tested for IgM anti-core hepatitis C virus by immunoassay. All patients were seropositive for IgG antibody to hepatitis C virus by second-generation ELISA; 25 had histologic cirrhosis and 57 chronic hepatitis. IgM anti-core was detected in 84/106 (79.2%) patients. HCV-RNA was tested by branched (bDNA) signal amplification assay or by polymerase chain reaction in 92 patients. RESULTS: All IgM-anti-HCV positive patients had detectable HCV-RNA. Seventy of 87 (80.5%) HCV-RNA-positive patients were IgM anti-core positive. Levels of IgM anti-HCV were significantly higher in patients with HCV-RNA detected by bDNA than in those who were bDNA negative, but there was no correlation between HCV-RNA concentrations and IgM anti-HCV levels. Of the 84 patients with positive results for IgM anti-core hepatitis C virus, 59 (70.2%) had abnormal alanine aminotransferase levels. The levels of IgM anti-core hepatitis C virus were likewise significantly higher in those with abnormal alanine aminotransferase levels. There was no difference in the percentage of patients with a positive IgM anti-HCV, or in levels of IgM anti-core hepatitis C virus in those with chronic hepatitis versus cirrhosis. CONCLUSIONS: These data suggest that the majority of patients with chronic hepatitis C virus infection are IgM anti-core hepatitis C virus positive, and the detection seems to be associated with viral replication and biochemical evidence of hepatic necrosis. IgM anti-core hepatitis testing may prove useful as an adjunct in the clinical assessment of patients with chronic hepatitis C.

Adolescent↗

PubMed1995

Hydatid disease.

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Animals↗

PubMed1993

Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose ingestion.

1. The objective of the present investigation was to study some of the possible mechanisms involved in the protective effect of sucrose ingestion against liver necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g) were submitted to the following experimental conditions for a period of 42 h: free access to a balanced commercial diet (Group I), an exclusive sucrose diet (Group II) and fasting (Group III). At the end of the experiment, hepatic cytochrome P450 levels were measured in 11 rats from each group, plasma antipyrine half-life (t1/2) was determined in 40 rats from each group, and hepatic glutathione (GSH) concentration in 10 rats from each group. GSH consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage) was also determined in 30 rats each from Groups II and III. 2. The liver of Group II rats presented a significant reduction of cytochrome P450 levels in the microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93, median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median 81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs 83.4 min for group I and 93.6 for group III) when compared with the rats of the two other groups. 3. Since the toxicity of acetaminophen depends on the production of a reactive metabolite by the cytochrome P450 system in the liver, we conclude that changes in this system brought about by exclusive sucrose ingestion for 42 h may explain the liver protection against the toxicity of a high dose of the drug even in the presence of a significant concomitant reduction in liver GSH levels.

Acetaminophen↗

PubMed1992

Polycystic hydatid disease (Echinococcus vogeli). Clinical, laboratory and morphological findings in nine Brazilian patients.

Polycystic hydatid disease occurs in neotropical zones and is caused by Echinococcus vogeli. The paca, a wild rodent, is the intermediate host and the final host is the dog. Seven cases of polycystic hydatid disease autochthonous to the Brazilian Amazon region are described. The disease was polycystic in all cases and diagnosis was based on anatomopathological findings. E. vogeli was identified by the shape and dimensions of the rostellar hooks. The liver was the organ most often involved (6/7), followed by the lungs (2/7) and mesentery (2/7), spleen (1/7) and pancreas (1/7). The main clinical manifestations were abdominal pain, hepatomegaly, jaundice, weight loss, anemia, fever, hemoptysis, palpable abdominal masses and signs of portal hypertension. Hepatic calcifications were detected in four cases. Two cases from the hinterland of the State of São Paulo are also reported. Both had calcified round structures in the liver, highly suggestive of calcified polycystic hydatids. The aim of the present report was to report on this relatively unknown hydatid disorder of Tropical America and to disseminate its clinical, ultrasound and radiological features.

Adult↗

PubMed1992

Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole.

Six patients with polycystic hydatid disease (PHD) were treated with 10 mg kg-1 day-1 albendazole. One patient was treated continuously for eight months and another for three months. In three other patients treatment was discontinuous, consisting of a series of at least three 30-day cycles separated by 15 days without treatment. The last patient was treated continuously with 12 mg kg-1 day-1 albendazole for 51 days and then with three 30-day cycles of treatment with 10 mg kg-1 day-1 separated by 15-day drug-free intervals. Follow-up ranged from 10-30 months. Considerable clinical improvement and cyst reduction or disappearance occurred in four patients. Clinical improvement, but no changes in the hepatic alterations detected by computerized tomography, occurred in the other two patients, although a pulmonary cyst disappeared in one of them. Adverse effects were proteinuria, alopecia, leucopenia, itching and discrete elevation in aspartate transaminase, all of them reversed after the end of treatment. These results indicate that albendazole is effective for the treatment of PHD.

Adult↗

PubMed1989

Effect of the intake of an exclusive sucrose diet on acetaminophen hepatotoxicity in rats.

1. To test the effect of a sucrose diet on acetaminophen hepatotoxicity, 20 male Wistar rats were fasted and 20 were maintained exclusively on a sucrose diet ad libitum for 66 h. After 42 h, acetaminophen (1 g/kg) was administered through an orogastric tube to 10 fasted animals and to 10 animals on the sucrose diet, or intraperitoneally to the remaining animals. Animals were killed 24 h later and blood was collected for the measurement of alanine and aspartate aminotransferase activity and the liver was removed for macroscopic and microscopic examination. 2. Plasma alanine and aspartate aminotransferase levels were significantly lower (P less than 0.001) in all animals maintained on the sucrose diet. Macroscopic examination revealed parenchymatous necrosis in 90% (18/20) of the fasted animals but in none of the animals fed sucrose. Microscopic examination confirmed the macroscopic findings and permitted the detection of liver necrosis in one additional fasted animal. 3. We conclude that ingestion of a sucrose diet protected the animals from the hepatotoxic effects of acetaminophen regardless of the route of administration of the drug.

Acetaminophen↗

PubMedDate not supplied

[Echinococcus vogeli cysts in paca liver (Cuniculus paca) native from the Acre State, Brazil].

Four of the patients with polycystic hydatid disease observed by us reported that they were aware of the presence of liver disease in the pacas hunted for food. The viscera of these animals were usually given to domestic dogs. All of our 7 patients reported contact with dogs that had previously ingested viscera of pacas. Examination of the liver considered to be diseased by one of the patients and removed from a paca killed in the same region (State of Acre, Brazil) from which the human cases originated showed the presence of hydatid cysts. The characteristics of the rostellar hooks of the protoscolex indicated that this was the larval form of Echinococcus vogeli. These observations confirm the participation of pacas in the biological cycle of E. vogeli and the pathway through which man may become an alternative intermediate host of this echinococcus.

Animals↗

PubMedDate not supplied

[Incidence of diverticular disease of the large bowel in non-chagasic and chagasic individuals with and without megacolon].

To study the frequency of association between two common colonic disease in our midst, chagasic megacolon and diverticular disease, we reviewed the barium enemas of 243 patients aged more than 35 years. Diverticula were detected in 22 (21.6%) of the 102 non-chagasic individuals, in 10 (35.7%) of 20 chagasics without megacolon, and in 14 (12.4%) of the 113 chagasics with megacolon. There was a statistically significant difference between the two chagasic groups, but not between each one of them and the non-chagasic group. The incidence of diverticula in the sigmoid colon of the non-chagasic group was significantly higher than in the sigmoid colon of the other two groups studied. Among the patients with association of megacolon and diverticular disease, the diverticula were always located in the nondilated portions of the large bowel. It is suggested that totally unfavorable conditions for the genesis and/or maintenance of diverticula exist in the dilated colon of chagasic patients.

Adult↗

PubMedDate not supplied

Abnormalities of the interdigestive migrating motor complex in a patient with carcinoid syndrome.

Intraluminal pressures of the gastric antrum, duodenum and jejunum were recorded for 206 min after a 12 h fast in a patient with carcinoid syndrome due to neoplasia of enterochromaffin cells of the ileum and with hepatic metastases. The most conspicuous alteration was a tachyrrhythmia of 16 waves/min predominating in the activity fronts of both duodenum and jejunum. Periods of 11-12 waves/min frequency appeared irregularly and the simultaneous occurrence of frequencies of 11 waves/min and 16 waves/min was also recorded. The gastric antrum was fully quiescent throughout the study. The alterations observed are presumed to be produced by substances secreted by the carcinoid tumor.

Duodenum↗