RESUMEN

Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.

Asunto(s)

RESUMEN

Mean platelet volume (MPV), a determinant of platelet function, is a newly emerging risk factor for atherothrombosis. The present study was designed to evaluate MPV in patients with obesity compared with non-obese control subjects. We selected 100 non-obese subjects and 100 subjects with obesity [body mass index (BMI) > or =30 kg/m(2)] matched for age and gender. The MPV was significantly higher in obese group than in non-obese control group (10.3 +/- 1.2 vs. 9.0 +/- 0.8 fl, p < 0.01). MPV was positively correlated with BMI in obese group (p < 0.05). Increased MPV may be a possible cause for increased cardiovascular risk in patients with obesity.

Asunto(s)

RESUMEN

BACKGROUND: Cardiovascular risk associated with impaired fasting glucose has been examined in various studies with conflicting results. During the last 10 years, several risk markers for atherosclerosis such as fibrinogen and D-dimer have been identified. The present study was designed to evaluate plasma fibrinogen and D-dimer levels in patients with impaired fasting glucose compared with normal subjects and those with type 2 diabetes mellitus. METHODS: Age-, sex-, and body mass index-matched 30 normal subjects, 30 patients with impaired fasting glucose (fasting glucose 110 to 125 mg/dl), and 30 patients with type 2 diabetes mellitus (fasting glucose >/= 126 mg/dl) were included in the study. RESULTS: The levels of plasma fibrinogen in patients with type 2 diabetes mellitus, impaired fasting glucose, and normal subjects were 449 (306 - 605) mg/dl, 348 (264 - 468) mg/dl, and 216 (179 - 260) mg/dl, respectively. Patients with impaired fasting glucose had significantly lower plasma fibrinogen levels than patients with type 2 diabetes mellitus (p < 0.05). There were significantly higher plasma fibrinogen levels in patients with impaired fasting glucose than in normal subjects (p < 0.05). The levels of plasma D-dimer in patients with type 2 diabetes mellitus, impaired fasting glucose, and normal subjects were 615 (505 - 768) mg/l, 518 (412 - 664) mg/l, and 424 (356 - 557) mg/l, respectively. Patients with impaired fasting glucose had significantly lower plasma D-dimer levels than patients with type 2 diabetes mellitus (p < 0.05). There were significantly higher plasma D-dimer levels in patients with impaired fasting glucose than in normal subjects (p < 0.05). The levels of plasma fibrinogen and D-dimer were related to fasting glucose in type 2 diabetes mellitus and impaired fasting glucose groups (p < 0.05). We also detected positive correlation between plasma fibrinogen levels and age in study groups (p < 0.05). CONCLUSION: Our data suggest that patients with impaired fasting glucose pose a hypofibrinolytic status and cardiovascular risk, although this was lower than in patients with type 2 diabetes mellitus.

Asunto(s)

RESUMEN

Tacrolimus (FK506) is a potent macrolide immunosuppressant used for prevention of organ transplant rejection following transplantation. Monitoring of blood tacrolimus concentrations is essential to assess organ rejection and toxicity, because of the agent's narrow therapeutic range, wide inter- and intraindividual pharmacokinetic variability as well as drug interactions mediated by alteration in cytochrome P450. Several methods have been developed to monitor tacrolimus; immunoassays, bioassays, and HPLC/MS. The purpose of this study was to compare two analytical methods: the well-established MEIA II tacrolimus immunoassay using the IMx analyzer and the new EMIT 2000 tacrolimus immunoassay on the Cobas Integra 400 system. Tacrolimus results obtained using the two methods have been compared on 180 whole blood samples from kidney and liver transplant patients. The analytical sensitivities of both methods were defined as 1.2 ng/mL for EMIT and 1.5 ng/mL for MEIA II. The within-run CVs (n = 15) obtained with four-level controls were 9.08%, 9.41%, 5.23% and 4.4% for EMIT 2000. The comparison showed the following relationship between two methods: MEIA = 1.08.EMIT + 0.20 (r =.893). In conclusion, the EMIT 2000 tacrolimus immunoassay is a reliable alternative for the MEIA II method to monitor tacrolimus in organ transplant recipients. It provides a valid quantitative measurement of tacrolimus with comparable % CVs in quality-control as well as patient blood samples. Additionally, the EMIT 2000 method provides a rapid analysis of a large number of samples in one run with a low turnaround time and possibilities to reanalyze critical samples.

Asunto(s)

Asunto(s)