In vitro evaluation of the cytotoxic and genotoxic effects of artemether,an antimalarial drug,in a gastric cancer cell line (PG100)

Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3‐(4,5‐methylthiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose‐dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml^?1 (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml^?1, for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml^?1, for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100. Copyright © 2011 John Wiley & Sons, Ltd.     

HIV AND HCV COINFECTION: PREVALENCE,ASSOCIATED FACTORS AND GENOTYPE CHARACTERIZATION IN THE MIDWEST REGION OF BRAZIL

A cross-sectional study on prevalence, associated factors and genotypedistribution of HCV infection was conducted among 848 HIV-infected patientsrecruited at reference centers in the Midwest Region of Brazil. The prevalencerate of HIV-HCV coinfection was 6.9% (95% CI: 5.2 to 8.6).In multivariable analysis, increasing age, use of illicit drugs (injectionand non-injection), a history of blood transfusion before 1994, and theabsence of a steady partnership were significant independent associated factorsfor HIV-HCV coinfection. The phylogenetic analysis based on the NS5B regionrevealed the presence of two major circulating genotypes of HCV: genotypes 1(58.3%) and 3 (41.7%). The prevalence of HIV-HCVcoinfection was lower than those reported in studies conducted with HIV-infectedpatients in different regions of Brazil, due to the fact that illicit drug useis not a frequent mode of HIV transmission in this region of Brazil. Serologicscreening of HIV-patients for HCV before initiating antiretroviral treatment, acomprehensive identification of associated factors, and the implementation ofeffective harm reduction programs are highly recommended to provide usefulinformation for treatment and to prevent HCV coinfection in these patients.     

Effect of oral contraceptives on vascular endothelial growth factor, Cox-2 and aromatase expression in the endometrium of uteri affected by myomas and associated pathologies

Background

The study was conducted to evaluate vascular endothelial growth factor (VEGF), Cox-2 and aromatase expression in the endometrium of uteri with myomas and other associated pathologies.

Study Design

Hysteroscopy was performed in 118 women of reproductive age with myomas and menorrhagia, 40 of whom were using a pill containing 75 mcg gestodene+30 mcg ethinylestradiol. Aromatase p450, VEGF and Cox-2 expression was detected using immunohistochemistry. Fisher's Exact Test and the Mann–Whitney test were used in the statistical analysis, with significance established at p<.05.

Results

In patients with myomas and menorrhagia, associated pathologies such as adenomyosis, endometrial polyps and endometriosis were found in 32%, 12% and 17% of cases, respectively. Aromatase, Cox-2 and VEGF expression was greater during the proliferative phase compared to the luteal phase of the cycle or following oral contraceptive use.

Conclusion

Endogenous progesterone or combined oral contraceptives are potent inhibitors of VEGF, aromatase and Cox-2 expression in the endometrium of patients with myomas and menorrhagia.     

Peripheral insulin resistance during treatment of chronic hepatitis C with peguilated interferon plus ribavirin

Patients with hepatitis C virus (HCV) infection present higher risk of developing type-2 diabetes mellitus (DM). However, the mechanism of this association and the role of antiviral treatment are still unclear. The objective of this study was to investigate the relationship between the use of peguilated interferon and the development of insulin resistance (IR) in these patients. METHODS: HOMA index was evaluated in 30 HCV-infected patients just before and during the first 6 months of treatment with peguilated interferon plus ribavirin. Anthropometrical parameters and glucose/cholesterol profile were also monitored. RESULTS: No changes in HOMA after 6 months of treatment were observed. Glucose levels decreased but not significantly (P = 0.059). Patients with higher HOMA index after 6 months of treatment also presented higher aminotransferase levels (P = 0.03), higher fat index on computed tomography (P = 0.011), longer time of exposure to the virus (P = 0.021), and a positive smoking history when compared to non-insulin resistant patients (P = 0.045). There was no influence of fibrosis stage on liver biopsy in the insulin-resistance development. CONCLUSIONS: No changes in the IR were observed after 6 months of treatment. Insulin resistance is related to the abdominal fat and anthropometrical parameters rather than to the antiviral treatment.     

Logistic regression analysis of potential prognostic factors for pulmonary thromboembolism

OBJECTIVE: To identify potential prognostic factors for pulmonary thromboembolism (PTE), establishing a mathematical model to predict the risk for fatal PTE and nonfatal PTE. METHOD: The reports on 4,813 consecutive autopsies performed from 1979 to 1998 in a Brazilian tertiary referral medical school were reviewed for a retrospective study. From the medical records and autopsy reports of the 512 patients found with macroscopically and/or microscopically documented PTE, data on demographics, underlying diseases, and probable PTE site of origin were gathered and studied by multiple logistic regression. Thereafter, the "jackknife" method, a statistical cross-validation technique that uses the original study patients to validate a clinical prediction rule, was performed. RESULTS: The autopsy rate was 50.2%, and PTE prevalence was 10.6%. In 212 cases, PTE was the main cause of death (fatal PTE). The independent variables selected by the regression significance criteria that were more likely to be associated with fatal PTE were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00 to 1.03), trauma (OR, 8.5; 95% CI, 2.20 to 32.81), right-sided cardiac thrombi (OR, 1.96; 95% CI, 1.02 to 3.77), pelvic vein thrombi (OR, 3.46; 95% CI, 1.19 to 10.05); those most likely to be associated with nonfatal PTE were systemic arterial hypertension (OR, 0.51; 95% CI, 0.33 to 0.80), pneumonia (OR, 0.46; 95% CI, 0.30 to 0.71), and sepsis (OR, 0.16; 95% CI, 0.06 to 0.40). The results obtained from the application of the equation in the 512 cases studied using logistic regression analysis suggest the range in which logit p > 0.336 favors the occurrence of fatal PTE, logit p < - 1.142 favors nonfatal PTE, and logit P with intermediate values is not conclusive. The cross-validation prediction misclassification rate was 25.6%, meaning that the prediction equation correctly classified the majority of the cases (74.4%). CONCLUSIONS: Although the usefulness of this method in everyday medical practice needs to be confirmed by a prospective study, for the time being our results suggest that concerning prevention, diagnosis, and treatment of PTE, strict attention should be given to those patients presenting the variables that are significant in the logistic regression model.     

Effects of partial isothermic immersion on the spirometry parameters of tetraplegic patients

STUDY OBJECTIVES: Our objective was to compare under controlled conditions the effect of immersion on spirometry parameters of patients with tetraplegia vs those of normal individuals.Design and patients: Twenty-three otherwise well tetraplegic subjects were compared to a control group of 11 similar healthy subjects before and during 5 to 15 min of isothermal immersion in water to shoulder level. RESULTS: Measured at baseline, tetraplegic subjects exhibited significant pulmonary restriction, characterized by a mean FVC of 54.9 +/- 14.6% of the predicted value (range, 23.2 to 80.4%), whereas all controls subjects had > 80% of predicted values. Immersion increased the FVC of tetraplegic patients an average of 18.4 +/- 18.7% above basal measurements, while that of the control group worsened (DeltaFVC, - 8.8 +/- 4.4%). Among the tetraplegic patients, the lower the preimmersion vital capacity, the greater the percentage of improvement following immersion (r = 0.79; 95% confidence interval, - 0.91 to - 0.56; p < 0.0001). No relationship was found between the time elapsed since cervical cord injury or its level and the degree of improvement. CONCLUSIONS: Water activities play an important role in the rehabilitation of patients with spinal cord injury. Immersion in isothermal water at shoulder level, under strictly controlled experimental conditions, reduces the vital capacity of normal individuals, while it improves in a group of patients with tetraplegia. The observed phenomenon seems to be mediated by an improvement in breathing mechanics, impaired by cervical cord injury.     

Theoretical and experimental investigations prove Nd: YAG laser treatment to be safe

The safety of the application of the Nd:YAG laser for hemostasis in emergency gastro-endoscopy when its irradiation is properly dosed is demonstrated on the basis of laboratory investigations as well as theoretical calculations on a mathematical model of internal scattering. The increased effectiveness of this laser compared with argon and CO₂ lasers in producing in-depth volume heating is shown to derive from the fortuitous combination of its low absorptivity with the scattering phenomenon.