Pravastatin attenuates carboplatin-induced cardiotoxicity via inhibition of oxidative stress associated apoptosis.

The objective of this study was to evaluate the cardiac toxicity induced by carboplatin, a second generation platinum-containing anti-cancer drug, and to test whether pravastatin can reduce this cardio-toxicity. In the present study, infusion of carboplatin (100 mg/kg) to mice resulted in decreased survival rates and abnormal cardiac histology, concomitant with increased cardiac apoptosis. In addition, treatment of cultured rat cardiomyocytes with carboplatin (100 muM for 48 h) caused marked apoptosis and increased caspase-3, -9, and cytochrome C, but decreased BCL-XL protein expression, and this was inhibited by reactive oxygen species (ROS) scavenger n-acetylcysteine. Furthermore, pretreatment of cardiomyocytes with pravastatin (20 microM) before carboplatin exposure significantly attenuated apoptosis and decreased caspase-3, -9, cytochrome C activity. Lastly, mice pre-treated with pravastatin before carboplatin treatment showed improved survival rate and cardiac function, with reduced cardiomyocyte apoptosis via activating Akt and restoring normal mitochondrial HAX-1 in heart tissue. In summary, our results show that carboplatin can induce cardiotoxicity in vivo and in cultured cells via a mitochondrial pathway related to ROS production, whereas pravastatin administration can reduce such oxidative stress thus prevented cardiac apoptosis. Therefore, pravastatin can be used as a cytoprotective agent prior to carboplatin chemotherapy.

Chronic hepatitis ameliorates anaemia in haemodialysis patients.

BACKGROUND: Study for influence of chronic hepatitis (CH) on anaemia in haemodialysis (HD) patients remains inconclusive. We aim to characterize the red cell status between CH and hepatitis-free groups among the HD population. METHODS: We retrospectively analysed 80 chronic HD patients from Taipei Medical University Hospital with monthly sampled biochemical study between December 2004 and December 2005. Data classified according to the hepatitis-free, chronic hepatitis B and C groups were expressed as mean +/- standard deviation. Student's t-test and anova were used to determine the mean difference for continuous variables. RESULTS: Age, Kt/V, systolic or diastolic blood pressure, body mass index, total cholesterol and triglyceride were not different between CH and hepatitis-free groups. HD duration (P = 0.0002), aspartate (P < 0.0001), alanine aminotransferase (P < 0.0001), alkaline phosphatase (P = 0.04), haemoglobin (P = 0.0066) and haematocrit (P = 0.002) were significantly more elevated in the CH group demanding less erythropoietin dose than in the hepatitis-free group. CONCLUSION: Our study demonstrated that lessened anaemia was observed in CH, which demanded less erythropoietin dose.

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case-Control Study.

BACKGROUND: Metformin use reduces the incidence and severity of stroke in patients with type 2 diabetes mellitus (DM). The benefits of metformin for stroke have not been examined in hemodialysis patients with DM. METHODS AND RESULTS: Using the National Health Insurance Research Database, we identified 17 760 patients with DM and new-onset hemodialysis between 2001 and 2013. Of these, 1898 patients hospitalized for either ischemic or hemorrhagic stroke were matched to 7592 control patients according to sex, age, and year of initial hemodialysis therapy by using incidence sampling. The association between metformin use and stroke risk was estimated using conditional logistic regression after adjustment for hemodialysis frequency, comorbidity, and prescribed medications. Metformin use was recorded before the date of stroke admission and the date of pseudostroke of the case and control patients, respectively. Results showed that hemodialysis patients with ischemic stroke were more likely to use metformin than the controls 1 year before the date of stroke admission (adjusted odds ratio: 1.64; 95% confidence interval, 1.32-2.04). The association was evident within 90 days before the index date (adjusted odds ratio: 1.81; 95% confidence interval, 1.27-2.60). The results were consistent with those of hemodialysis patients with hemorrhagic stroke. Metformin use remained a risk factor for stroke in patients treated with antihypertensive, sulfonylurea, and antiplatelet drugs. CONCLUSIONS: This nested case-control study is the first to show that metformin use is associated with stroke risk in hemodialysis patients with DM. We suggest that metformin should not be used by hemodialysis patients with DM.

Association of Processed Meat Intake with Hypertension Risk in Hemodialysis Patients: A Cross-Sectional Study.

In this cross-sectional study, we hypothesized that hemodialysis patients consuming greater processed meat is associated with hypertension risk, which can be partly explained by the high sodium content in processed meat. From September 2013 to May 2014, one hundred and four patients requiring chronic hemodialysis treatment were recruited from hemodialysis centers. Data on systolic blood pressure and diastolic blood pressure before receiving dialysis, and 3-day dietary records of the recruited patients were collected. HD patients with systolic and diastolic blood pressures greater than140 mmHg and higher than 90 mmHg, respectively, were considered hypertension risk. Protein foods were divided into 4 categories: red meat, white meat, soybeans, and processed meat (e.g., sausage and ham). In a model adjusted for energy intake and hypertension history, additional servings of processed meats was positively associated to systolic blood pressure >140 mmHg (odds ratio [95% confidence interval]: 2.1 [1.0-4.3]), and diastolic blood pressure > 90 mmHg (odds ratio: 2.5 [1.2-5.5]). After adjustment for dietary sodium contents or body mass index (BMI), most associations were substantially attenuated and were no longer significant. In systolic blood pressure greater than140 mmHg, one serving per day of red meats (ß = -1.22, P < .05) and white meats (ß = -0. 75, P = .05) was associated with a reduced risk compared with one serving per day of processed meats. Similarly, compared with one serving per day of processed meat, a reduced risk of diastolic blood pressure higher than 90 mmHg was associated with one serving per day of red meat (ß = -1. 59, P < .05), white meat (ß = -0. 62, P < .05). Thus, in these hemodialysis patients, intake of processed meat is significantly positively associated with higher blood pressure risk, and both sodium contents in processed meat and BMI significantly contributes to this association.