Preliminary study of the level of visfatin and the relationship with insulin resistance in Chinese patients with chronic hepatitis C.

BACKGROUND: Many studies have suggested that visfatin expression is closely related to the occurrence of insulin resistance (IR), while the precise role of visfatin in the regulation of IR in chronic hepatitis C (CHC) is not clear. METHODS: We investigated fasting glucose, fasting insulin (FINS), C peptide, visfatin, visfatin mRNA, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and other parameters of 315 patients with CHC and 150 control cases in China. Meanwhile we collected clinical and other laboratory data for further analysis. RESULTS: Compared with the control group, the CHC group had a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), the AST to platelet ratio index (APRI), ratio of AST to ALT (AAR), gammaglutamyl trans-peptidase, IL-6, TNF-α, visfatin, visfatin mRNA, FINS, fasting C peptide, and IR index. The visfatin, visfatin mRNA, insulin, IR index, Homaß cell function index (HBCI), and fasting ß-cell function index (FBCI) of the subjects with high body mass index (BMI) from the CHC sub-group were significantly higher than the normal BMI sub-group of CHC patients. We found a positive correlation between visfatin, visfatin mRNA and BMI, IL-6, TNF-α, and IR index. CONCLUSION: Our data suggest that visfatin may be related to IR in Chinese CHC patients.

Alanine aminotransferase: a clinical and regulatory tool for detecting liver injury-past, present, and future.

Assay of the serum activity of the enzyme alanine aminotransferase (ALT) has become the primary screening tool for detecting acute liver injury. But what does an elevated value mean? Not what it is too often mistakenly believed to indicate. It is not a test of liver function. It does not necessarily predict worse effects to come (in a given person). It is not a valid measure of severity of liver injury or dysfunction. It is too unspecific to be reliable in screening for relatively rare effects on the liver. Although these are substantial limitations, ALT is a very useful biomarker if understood and used properly. It is important to consider how and why these erroneous concepts came to have such wide acceptance, and how elevations of ALT activity for evaluating patients and subjects under study might be interpreted better.

Hepatocurative and antioxidant profile of HP-1, a polyherbal phytomedicine.

HP-1 a herbal formulation comprising of Phyllanthus niruri and extracts of Terminalia belerica, Terminalia chebula, Phyllanthus emblica and Tinospora cordifolia has been evaluated for hepatoprotective activity against carbon tetrachloride (CCl4) induced toxicity. Results show that HP-1 reversed the leakage of lactate dehydrogenase (LDH) and glutamate pyruvate transaminase (GPT) and prevented the depletion of glutathione (GSH) levels in a primary monolayer culture of rat hepatocytes (in vitro). HP-1 attenuated the serum toxicity as manifested in elevated levels of transaminases (glutamate oxaloacetate transaminase (GOT), and GPT) The antioxidative enzymes in liver (catalase and superoxide dismutase (SOD)) were restored to normal values after the oral administration of HP-1. HP-1 suppressed the formation of the superoxide anion radical and reduced CCl4 mediated lipid peroxidation (LPO). Silymarin and antioxidants (ascorbic acid, beta-carotene and alpha-tocopherol) were used for comparison. The present study showed that HP-1 is a potential hepatoprotective formulation with an additional attribute of being anti-peroxidative.

Plasma fibrinogen level is an important determinant of prolonged euglobulin clot lysis time in hemodialysis patients.

The euglobulin clot lysis time (ECLT), a traditional measure of plasminogen activation, directly depends on plasma fibrinogen (FBG) level. This fact was neglected in studies concluding that prolonged ECLT in chronic hemodialysis (HD) patients pointed exclusively to impaired fibrinolysis. We studied the relations between ECLT and plasma FBG levels in HD patients in relation to certain hepatic and inflammatory markers. Median ECLT of 320 minutes (range, 150 to 620 minutes) and plasma FBG of 306 mg/dL (range, 171 to 553 mg/dL) were higher in 75 HD patients than in 60 healthy controls (Mann-Whitney p < 0.0001). There were positive associations between these parameters both in the patients (Spearman p = 0.273, p = 0.018) and the controls (p = 0.672, p < 0.0001). The FBG-corrected ECLT (plasma FBG/ECLT) (in mg/[min x dL]) in the patients (0.92 [range, 0.47 to 2.43]) was not different (p = 0.065) from that in the controls (1.08 [0.58 to 1.67]). In the patients, serum alanine aminotransferase inversely correlated with ECLT (p = -0.306, p = 0.008) and FBG (p = -0.310, p = 0.007), whereas serum C-reactive protein was associated positively with these variables (p = 0.383, p = 0.0007; p = 0.477, p < 0.0001, respectively). The FBG-corrected ECLT was not related to either marker. In conclusion, increased plasma FBG level, a continuum between liver dysfunction and stimulation by chronic inflammation, is an important determinant of prolonged ECLT in HD patients. The FBG-corrected ECLT value suggests that baseline activation of fibrinolysis is normal in these patients, and that this simple index could be useful in its laboratory assessment.

Population distribution profiles of the activities of blood alanine and aspartate aminotransferase in the normal F344 inbred rat by age and sex.

Data on the blood enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were collected from control male and female F344 rats participating in toxicity studies at 17, 30, 56, 80 and 106 weeks of age. The data were skewed to the right with significant deviation from normality. Applying the Box-Cox transformation, it was concluded that approximately normal distributions could be obtained by using the reciprocal transformation. In general, the males showed a greater degree of heterogeneity for both enzymes. Enzyme activities at 17 weeks were lowest for both ALT and AST. There was a high correlation between the activities of blood ALT and AST, with some animals showing dramatic transient increases. Significant differences among studies with respect to the enzyme activities in rats of the same age were demonstrated.

[Studies on enzyme activities relating to amino acid mobilization in biopsied muscles].

We evaluated glutamine synthetase (GS) and alanine aminotransferase (GPT) activities in biopsied muscle from 40 cases of various neuromuscular diseases. GS and GPT catalyze the synthesis of glutamine and alanine, respectively, from amino acids derived in part from the breakdown of muscle proteins. The subjects were 7 cases of muscular dystrophy; 1 Duchenne type (DMD), 3 limb-girdle type, 2 facioscapulohumeral type (FSH), 1 Fukuyama type (FCMD); and 1 myotonic dystrophy (MyD); 5 mitochondrial myopathies; 11 inflammatory myopathies including 6 polymyositis and 3 myopathy associated with collagen disease; 5 endocrinological myopathies including 2 periodic paralysis; and, 11 cases of neurogenic amyotrophies [4 amyotrophic lateral sclerosis (ALS), 4 spinal progressive muscular atrophy (SPMA) and 3 other types]. Control subjects were 8 patients with thigh operations. Biopsied muscle was homogenized and assayed for GS activity by the method of Smith et al.; GPT was assayed by commercial kit. Protein was assayed by the method of Lowry et al. Enzyme activities between mean -2SD and mean +2SD of controls were considered to be the normal range. GS activity in control subjects was 28.22 +/- 7.13 (mean +/- SD) nmol glutamine formed/mg protein/hr. Fifteen of 40 cases showed increased enzyme activity, including DMD and FCMD, the acute phase of polymyositis, and periodic paralysis. GPT activity in controls was 16.56 +/- 4.05 IU/mg protein. Sixteen of 40 patients showed increased enzyme activity: FCMD, FSH, MyD, inflammatory and endocrinological myopathy, and ALS. On the other hand, mitochondrial myopathy showed significantly decreased activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Atypical segregation in the GPT group system. Determination of types and activity of enzyme in families.

Examination of GPT system in 5418 paternity cases confirmed the elimination of maternity in 21 cases. The study of 12 probant families displayed the occurrence of opposite homozygous types in parents and children. The result obtained showed the presence of GPT0 gene in the families examined. Similar results were obtained by examining five families of alleged fathers whose paternity was eliminated on the same basis. In 12 families the activity of GPT was determined. In majority of subjects with GPT0 gene, markedly lowered activity was observed. This also concerned several homozygous subjects who were identical with their parents. The lowered activity of the enzyme is not present in all subjects with a "silent gene", and therefore, its examination cannot be used for detection of the gene.

Suppression of lymphocyte activation by a protein released from isolated perfused rat liver.

Isolated rat liver perfusates contain a substance which inhibits 3H-thymidine uptake by phytohemagglutinin-stimulated human peripheral blood lymphocytes in a dose-dependent, noncytotoxic fashion. Suppression is not due to interference of lymphocyte-phytohemagglutinin interaction or dilution of the thymidine pool. Complete inhibition of thymidine uptake is achieved with less than 1.0 microgram of material per ml (which is a potentially achievable concentration in vivo). The release of this material is directly and quantitatively associated with hepatocellular injury as measured by release of glutamic pyruvate transaminase. The material is a highly basic protein with a molecular weight of approximately 65,000 to 80,000 daltons. It is a product of the hepatocyte rather than of nonparenchymal liver cells. Liver-derived materials, such as the presently described molecule, may play a role in in situ regulation of lymphocyte function during immunologically mediated liver disease.