Assessment of protective role of polyherbal preparation, Livina, against anti-tubercular drug induced liver dysfunction

The present study evaluated the possible protective role of Livina (a polyherbal preparation) against anti-tubercular therapy (ATT)-induced liver dysfunction in patients of pulmonary tuberculosis. Patients were given intensive phase treatment with 4-drugs (rifampicin, INH, pyrazinamide and ethambutol) used for anti-tubercular therapy for 2 months, followed by a 4-month continuous phase treatment with 2 drugs (rifampicin and INH) under clinical advice and supervision. Both qualitative and quantitative measures of liver function were assessed, at different time intervals, before and after ATT. Analysis of data showed that the incidence of qualitative manifestations of liver dysfunction were greater in the placebo treated group as compared to the test drug group. None of the patients of either group showed clinical jaundice. Most signific changes ant were observed in the SGOT and SGPT levels in the placebo group, wherein the levels of both enzymes were higher at 4 and 8 weeks post-ATT, as compared to the respective baseline (0 week) values. When Livina (2 capsules twice daily) was given with ATT drugs, incidence of qualitative manifestation of liver dysfunction was insignificant and SGOT and SGPT levels were also significantly lower than the placebo+AITT drugs treated group. These results indicate that the test drug (Livina) was efficacious, against ATT-induced hepatic dysfunction in patients of pulmonary tuberculosis.     

First signs of anaphylaxis

A prospective study of 208 patients treated for up to 12 months with isoniazid (INH^®) for tuberculosis prophylaxis was made. Levels of serum glutamic oxaloacetic acid transaminase (SGOT) became elevated in 20 percent of the adults followed and in 30 percent predominantly nonspecific symptoms developed, in 11 percent simultaneously with SGOT elevation; SGOT levels became elevated in two of 33 children and 1 was symptomatic. Mild SGOT elevations in asymptomatic adults were self-limited; however, a small percentage of symptomatic adults showed prolonged SGOT elevation for months after INH was completed. Results of liver biopsy studies in the early stages of SGOT elevation generally showed portal and periportal lymphocytic infiltrations with lesser numbers of plasma cells, neutrophils and eosinophils.     

Liver function tests during amoebic liver abscess formation in indomethacin-treated hamsters

Establishment of Entamoeba histolytica infection is facilitated through macrophage effector disruption by a prostaglandin E2 (PGE2)-mediated mechanism. Infection severity may be measured by weight of abscess formed. Indomethacin (Indo) treatment of infected hamsters reduced abscess weight by 30% at 7 days post-infection presumably by inhibition of PGE2. To explain reductions in abscess development by Indo treatment, we determined liver functionality in Indo-treated or untreated animals, either healthy or infected. Determinations of serum glutamic oxaloacetic (SGOT) and glutamic pyruvic (SGPT) transaminases, serum alkaline phosphatase (SAP), total serum protein (TSP), and bilirubinemia were done. SGOT, SGPT, and SAP activities showed a significant increase in their values by 600% at seven days post-infection in infected animals in both conditions; nonstatistical differences were found between animals treated or not. This increase did not correlate with the percentage of damage. Infected nontreated hamsters showed TSP levels 30% below normal group (P < 0.05). Infected Indo-treated hamsters had no significant differences compared to normal values. Infected nontreated animals showed an increase in bilirubin, particularly in indirect bilirubin, whereas infected Indo-treated hamsters showed total bilirubin values lower than normals (P < 0.05), with a decrease in direct bilirubin levels. Our results demonstrated that E. histolytica infection in hamsters produces similar abnormalities in liver function as it does in humans, and that the beneficial effect of Indo treatment on amoebic abscess development is not related with an improvement of liver functionality.     

Coagulation factor therapy for hemophilia: relation to hepatitis B and to liver function.

Therapy with concentrated coagulation factors has greatly improved the management of hemophilia, but the consequence of repeated infusion of these blood products are unknown. Hepatic dysfunction is frequent in patients with hemophilia, and the use of these products may be responsible. The relation between liver function and both the frequency and type of therapy with coagulation factors was studied in a group of patients with hemophilia. Of the 36 patients studied, 75% were found to have antibody to hepatitis B surface antigen in their serum and 44% had high levels of serum glutamic oxaloacetic transaminase (SGOT). The infusion of concentrated coagulation factor more than once per year was significantly associated with the presence of antibody to hepatitis B surface antigen and with a high SGOT level. The patients treated with concentrates prepared from blood obtained from large donor pools were significantly more likely to have antibody to hepatitis B surface antigen in their serum but no more likely to have a high H-SGOT level than the patients treated exclusively with cryoprecipitate, plasma or whole blood. These findings suggest that in patients with hemophilia the frequency of coagulation factor treatment may be a more important determinant of hepatic dysfunction than the type of treatment.     

Diagnostic efficacy of tests for the detection of iron overload in chronic liver disease.

The value of tests for the detection of body iron overload was investigated in 8 aptients with clinically manifest primary hemochromatosis, 12 patients with cirrhosis and iron overload and 20 patients with liver disease and low or normal iron stores. Iron overload was defined as the presence of stainable iron in more than 50% of hepatocytes in a liver biopsy specimen. The percentages of patients with a true-positive (abnormal) or true-negative (normal) result were: serum iron concentration 65%, transferin saturation 85%, serum ferritin concentration 78%, serum ferritin:serum glutamic oxaloacetic transaminase (SGOT) index 78%, percent iron absorption 58%, percent iron absorption in relation to serum ferritin concetration 80% and percent iron absorption in relation to serum ferritin:SGOT index 93%. The calculated predictive value of a normal test result for the exclusion of iron overload in patients with liver disease, a group with an assumed prevalence of iron overload of 10%, was 98% to 99% for transferrin saturation and serum ferritin concentration used alone and 100% for these measures used together; the predictive value of an abnormal result for the diagnosis of iron overload was less than 50% for all of the above measures used alone or in combination. Hence, in patients with an increased serum ferritin concentration or transferrin saturation, or both, determination of the hepatocellular iron content of a specimen from a percutaneous liver biopsy is required for the diagnosis of iron overload.     

Effect of oestrogen on liver function of prostatic cancer patients

Liver function of patients with cancer of the prostate gland was studied while they were receiving oestrogen therapy. When synthetic oestrogens were given, raised values of serum aspartate and alanine amino-transferase (S.G.O.T. and S.G.P.T.) were found in about 30–50% of them. As treatment continued the increased values usually returned to normal levels. No serious liver damage was observed, though the serum bilirubin content rose temporarily in some patients.     

Adverse Reactions to Daily and Intermittent Rifampicin Regimens for Pulmonary Tuberculosis in Hong Kong

This paper reports the nature, incidence, and severity of adverse reactions to regimens of rifampicin and ethambutol given once weekly, twice weekly, or daily and to a standard reserve regimen in a total of 330 Chinese failure patients who completed at least six months'' chemotherapy in a therapeutic comparison in Hong Kong.The adverse reactions which occurred on the regimens of intermittent rifampicin were termed cutaneous, abdominal, “flu”, and respiratory; in addition, purpura and abnormal liver function tests were encountered. There was an association of adverse reactions with the interval between doses and with the dose size of rifampicin, the highest incidence occurring with once-weekly rifampicin in high dosage. A procedure was developed for managing adverse reactions to intermittent rifampicin. Of 202 patients treated with intermittent rifampicin 60 developed adverse reactions, but in only 7 (3%) was it necessary to terminate the drug, though a further 10 (5%) were changed to daily rifampicin. On daily rifampicin, generalized hypersensitivity, cutaneous reactions, (one with purpura), and impaired liver function were encountered. Adverse reactions on the standard ethionamide, pyrazinamide, and cycloserine regimen were frequent and some were serious.     

Glutamate dehydrogenase: a reliable marker of liver cell necrosis in the alcoholic.

The usefulness of blood enzyme determinations as markers of liver necrosis was tested in 100 alcoholics who underwent biopsy during clinical investigation. Mean values of glutamate dehydrogenase (GDH), serum aspartate and alanine transferase (SGOT and SGPT), ornithine carbamoyltransferase (OCT), and gamma-glutamyltranspeptidase (gamma-GTP) tended to rise with increasing liver cell necrosis, though values of SGOT, SGPT, OCT, and gamma-GTP showed considerable overlap between the 32 patients with histologically proved hepatitis and the 68 without. By contrast, GDH values showed virtually no overlap between patients with and without hepatitis, and a value of two and a half times the normal value discriminated between the two groups. Because of its easy determination and its reliable reflection of liver cell necrosis the GDH concentration should be estimated routinely in alcoholic patients.     

Serum alpha-glutathione S-transferase as a sensitive marker of hepatocellular damage in patients with cystic fibrosis

The aim of the study was to evaluate serum a-glutathione S-transferase (s-GSTA) levels in patients with cystic fibrosis (CF) and to compare s-GSTA with other liver function tests and with a hepatic ultrasound scan (US). The cytosolic enzyme, alpha-glutathione S-transferase is predominantly found in the liver and is distributed uniformly in the liver tissue. In our study s-GSTA levels were measured in 37 CF patients aged 1 to 28 years (mean age 10.4 years, 24 males). The control group consisted of 27 patients aged 2 to 17 years (mean age 8.5 years, 18 males). The presence of hepatobiliary abnormalities was assessed by clinical examination, ultrasound scan, s-GSTA, and conventional liver enzymes: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and gama-glutamyl transferase (GMT). The calculated 5-95 % range of s-GSTA for the control group was 0.098-2.54 microg/l, for the CF group 0.43-9.76 microg/l. Mean s-GSTA level in the control group was 1.55 microg/l (S.D.=1.57), and 2.05 micro/l (S.D.=2.60) in the CF group. In the group of CF patients, the serum levels were significantly higher than in the control group (P<0.01). No significant correlation existed in the CF group between s-GSTA and conventional liver tests (ALT, AST, ALP and GMT). Four patients in the CF group had hepatobiliary abnormalities detectable by conventional liver tests, s-GSTA and US. Four patients had abnormal s-GSTA, while conventional liver tests and US were normal. One other patient had abnormal hepatic US, but normal standard liver tests and s-GSTA. The study has suggested that a raised s-GSTA level might be a marker of possible pathological changes of the hepatobiliar system in CF patients. Serum GSTA seems to be a more sensitive marker than transaminases for the monitoring of hepatocellular integrity and as an early predictor of hepatic damage.     

Laboratory Studies in Acute Alcoholics

Laboratory studies on 109 acutely intoxicated male and female alcoholics admitted to the general medical wards of a community general hospital were undertaken. Initially the program was designed to study the thyroid function of these patients, as a previous report had noted that large numbers of alcoholics were thyroid-deficient. During the study, however, other laboratory examinations, which might be confusing or misleading in alcoholics, were also measured. These additional estimations included the serum glutamic oxaloacetic transaminase (SGOT), the serum cholesterol and the serum amylase. No patients were found to be hypothyroid. The results of the tests indicate the need for caution in interpreting SGOT and serum amylase results in acute alcoholics.     

Ocimum sanctum aqueous leaf extract provides protection against mercury induced toxicity in Swiss albino mice

HgCl2 (5.0 mg/kg body weight) induced toxicity led to significant elevation of lipid peroxidation (LPO) level but decline in the glutathione content in liver of Swiss albino mice. In serum of HgCl2 treated mice there was significant elevation in serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities but significant decline in the alkaline phosphatase activity. Animals treated with O. sanctum extract (10 mg/kg body weight, po) before and after mercury intoxication showed a significant decrease in LPO level, SGOT and SGPT activities and increase in serum alkaline phosphatase activity and glutathione (GSH) content. Ocimum treatment alone did not alter SGOT, SGPT and alkaline phosphatase activities but significantly enhanced reduced glutathione. The results suggest that oral administration of Ocimum extract provides protection against HgCl2 induced toxicity in Swiss albino mice.     

Hemostatic Dysfunction Is Increased in Patients with Hepatosplenic Schistosomiasis Mansoni and Advanced Periportal Fibrosis

Background

Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis.

Methodology/Principal Findings

Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29), including raised serum transaminases (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n = 38) had lower levels of protein C compared to those with only central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.

Conclusion/Significance

This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.     

Molecular and genetic analyses of arylamine N-acetyltransferase polymorphism of rabbit liver

A cDNA clone encoding the full coding region of polymorphic arylamine N-acetyltransferase was isolated from rabbit liver and expressed in Chinese hamster ovary cells. The expressed enzyme acetylated 2-aminofluorene, procainamide, sulfamethazine, and p-aminobenzoic acid at equivalent rates. N-Acetyltransferase activity was measured in 17 rabbits from an inbred colony which were classified into rapid, intermediate, and slow acetylators. The livers of the rapid and intermediate acetylators efficiently acetylated all four substrates, while the liver from the slow acetylator showed a low but significant activity with p-aminobenzoic acid. Immunoblot and Northern blot analyses of rabbit livers indicated that the differences in N-acetyltransferase activity were due to differences in N-acetyltransferase protein and mRNA content. Genomic clones of N-acetyltransferase were isolated from the rapid and slow acetylator rabbits. The nucleotide sequence of the gene from rapid acetylator rabbit was identical to that of the cDNA, while the sequence of the gene from slow acetylator rabbit was homologous, but not identical, to the cDNA sequence. Genomic Southern blot and polymerase chain reaction analyses of the genomic DNAs and cDNAs from the three types of acetylator indicated that the gene for polymorphic arylamine N-acetyltransferase is totally deleted in the slow acetylator rabbit, while the gene from slow acetylator rabbit is expressed in all rabbits and might encode another N-acetyltransferase. Thus the genetic mechanism of N-acetyltransferase polymorphism in rabbit liver is essentially different from that of human liver as demonstrated in this laboratory (Ohsako, S., and Deguchi, T. (1990) J. Biol. Chem. 265, 4630-4634; Deguchi, T., Mashimo, M., and Suzuki, T. (1990) J. Biol. Chem. 265, 12757-12760).     

Prognostic significance of acute systolic hypertension after myocardial infarction.

The clinical behaviour and mean peak serum aspartate aminotransferase (SGOT) values of 106 patients admitted to a coronary care unit with acute myocardial infarction who displayed acute systolic hypertension were studied. Another 106 normotensive patients with acute myocardial infarction acted as controls. Neither group had established hypertension. The mortality rate, incidence of cardiac failure, major arrhythmias, and mean peak SGOT were significantly greater in the hypertensive group, within which the duration of hypertension was correlated with mean peak SGOT levels--through there was no definite relation between the height of systolic or diastolic pressure and SGOT. Transient systolic hypertension after acute myocardial infarction was therefore associated with a relatively poor prognosis, but our observations suggest that patients with a systolic blood pressure of at least 170 mm Hg might benefit from early hypotensive treatment.     

Characterization of the protective effects of melatonin and related indoles against alpha-naphthylisothiocyanate-induced liver injury in rats

The protective effect of melatonin, 6-hydroxymelatonin and N-acetylserotonin against alpha-naphthylisothiocyanate (ANIT)-induced liver injury was investigated and compared in rats injected once with the hepatotoxicant (75 mg/kg body weight). In rats injected with ANIT alone, liver injury with cholestasis developed within 24 h, as indicated by both serum levels of alanine aminotransferase (SGPT) and aspartic acid aminotransferase (SGOT) activities and serum total bilirubin concentration. The administration of melatonin or 6-hydroxymelatonin (10 mg/kg body weight) to ANIT-injected rats reduced significantly the serum levels of both SGPT and SGOT and the serum total bilirubin concentration. For all hepatic biochemical markers, melatonin was more effective that 6-hydroxymelatonin. By comparison, the administration of N-acetylserotonin (10 mg/kg body weight) to ANIT-injected rats did not reduce the serum levels of either hepatic enzymes or the serum total bilirubin concentration. In ANIT-injected rats, hepatic lipid peroxidation (LPO) was significantly higher than in control animals and this increase was significantly reduced by either melatonin, 6-hydroxymelatonin or N-acetylserotonin. Furthermore, ANIT treatment caused a significant reduction in liver microsomal membrane fluidity and this reduction was completely reversed by the three indoles. The liver from ANIT-injected rats showed several histopathological alterations; above all there was an acute infiltration of polymorphonuclear neutrophils and an increase in the number of apparent apoptotic hepatocytes. The concurrent administration of melatonin reduced the severity of all morphological alterations, specially the neutrophil infiltration and the number of presumed apoptotic cells. On the contrary, the administration of 6-hydroxymelatonin or N-acetylserotonin did not provide any protective effect in terms of the histopathological alterations. These results indicate that melatonin protects against ANIT-induced liver injury with cholestasis in rats, and suggests that this protective effect is likely due to its antioxidant properties and above all to its capacity to inhibit liver neutrophil infiltration, a critical factor in the pathogenesis of ANIT-induced liver injury. 6-hydroxymelatonin, although able to provide partial protection against the ANIT-induced hepatic injury, probably through its antioxidant properties by mechanisms that are unclear, was unable to reduce neutrophil infiltration. Finally, N-acetylserotonin in the experimental conditions of this study, only exhibited some antioxidant protection but had no protective effect against ANIT-induced hepatic damage.     

利福平导致严重血小板减少1例

利福平主要用于结核病的治疗,能引起血小板减少等不良反应。本病例使用利福平后出现严重血小板减少,血小板下降至4×10⁹/L,立即停用利福平并输注血小板后血小板恢复正常。因此,在利福平使用过程中应密切观察病情,监测血常规、肝肾功能等,及时发现不良反应,必要时立即停药,并对血小板明显下降者(<30×10⁹/L)给予补充血小板等治疗。对明确由利福平引起血小板减少者,治疗时应不再使用该药,以避免药物不良事件的发生。     

Evaluation of acetylator phenotype,renal function and serum sulfadiazine levels in patients with paracoccidioidomycosis treated with cotrimazine (a combination of sulfadiazine and trimethoprim)

The authors evaluated the relationships among renal function, acetylator phenotype and serum sulfadiazine levels in 22 patients with paracoccidioidomycosis treated with 1 tablet of cotrimazine (a combination of 820 mg sulfadiazine and 180 mg trimethoprim) administered orally every 12 hours.Fifteen patients (68.18%) presented free sulfadiazine levels above 50 g/ml, 6(27.28%) presented serum levels above 40 g/ml, and 1(4.54%), levels lower than 40 g/ml, this being the patient in which treatment failed. The highest free sulfadiazine levels were obtained in slow acetylator patients with reduced renal function. One patient with neuroparacoccidioidomycosis presented free sulfadiazine levels in cerebrospinal fluid corresponding to 55% of the serum levels.Finally, the authors consider cotrimazine to be an important therapeutic alternative for neuroparacoccidioidomycosis and conclude that administration every 12 hours can provide therapeutic sulfadiazine levels. They also suggest that when the sulfadiazine-trimethoprim combination is used, the therapeutic levels of sulfadiazine should be above 40 g/ml.     

Bleeding time in patients with hepatic cirrhosis.

OBJECTIVE--To determine the frequency of an abnormal bleeding time in patients with cirrhosis and to relate this to known factors that affect primary haemostasis and to the severity of liver disease. DESIGN--Prospective clinical and laboratory study in patients admitted for complications or investigations of liver disease. SETTING--Royal Free Hospital hepatobiliary and liver transplantation unit. SUBJECTS--100 Consecutive inpatients aged 17-74 with various forms of cirrhosis, including alcoholic, biliary, autoimmune, viral, and cryptogenic. At least 10 days had elapsed since any episodes of bleeding, resolution of sepsis, or alcohol intake. No patient was taking any drug known to affect primary haemostasis. MAIN OUTCOME MEASURES--Bleeding time as measured with the Simplate double blade template device. A bleeding time longer than 10 minutes was considered abnormal. Other measures were platelet count, prothrombin time, partial thromboplastin time, packed cell volume, and blood urea, serum bilirubin, and serum albumin concentrations, all measured on each subject at the same time by standard laboratory methods. RESULTS--A weak but significant correlation existed between the bleeding time and the platelet count (rs = 0.483; p less than 0.001). There were significantly lower platelet counts, longer prothrombin times, and higher blood urea and serum bilirubin concentrations in the 42 patients with bleeding times of 10 minutes or more compared with the 58 patients with bleeding times less than 10 minutes. Multiple linear regression analysis showed that the bilirubin concentration as well as the platelet count was independently correlated with the bleeding time. The combination of a platelet count greater than 80 x 10(9)/l and a prothrombin time less than 17 seconds (usually taken as safe limits for performing routine liver biopsy) did not predict a normal bleeding time. Ten of 39 patients fulfilling these criteria had a prolonged bleeding time. CONCLUSIONS--Prolonged bleeding time is common in patients with cirrhosis, even in those with prothrombin times and platelet counts within "safe limits" for invasive procedures. The severity of liver disease as assessed by the bilirubin concentration plays an important part in determining the bleeding time in cirrhosis. The bleeding time should be measured when assessing patients for invasive procedures who have a raised bilirubin concentration or poor hepatic function, even if the platelet count and prothrombin time are considered adequate.