A Systematic Review and Meta-Analysis of Ginkgo biloba in Neuropsychiatric Disorders: From Ancient Tradition to Modern-Day Medicine.

Ginkgo biloba (Gb) has demonstrated antioxidant and vasoactive properties as well as clinical benefits in several conditions such as ischemia, epilepsy, and peripheral nerve damage. Additionally, Gb is supposed to act as potential cognitive enhancer in dementia. So far, several trials have been conducted to investigate the potential effectiveness of Gb in neuropsychiatric conditions. However, the results of these studies remain controversial. We conducted a systematic review and a meta-analysis of three randomised controlled trials in patients with schizophrenia and eight randomised controlled trials in patients with dementia. Gb treatment reduced positive symptoms in patients with schizophrenia and improved cognitive function and activities of daily living in patients with dementia. No effect of Gb on negative symptoms in schizophrenic patients was found. The general lack of evidence prevents drawing conclusions regarding Gb effectiveness in other neuropsychiatric conditions (i.e., autism, depression, anxiety, attention-deficit hyperactivity disorder, and addiction). Our data support the use of Gb in patients with dementia and as an adjunctive therapy in schizophrenic patients.

Hemoglobin trends in isolated coronary artery bypass grafting performed off-pump and with standard and mini circuits.

The comparison of hemodilution at the end of surgery is of limited use as it represents only a snapshot of a dynamic phenomenon. This study was undertaken to compare the perioperative hemoglobin curves of isolated coronary artery bypass grafting performed with minimized extracorporeal circulation, traditional cardiopulmonary bypass, and off-pump technique. The propensity score method was used to select three groups of patients, homogenous regarding preoperative and operative data, who underwent isolated coronary artery bypass grafting. A generalized linear mixed model was used for estimating differences in perioperative hemoglobin trends among groups. The three groups were each composed of 50 patients with no differences in demographic data, preoperative risk profile, preoperative hemoglobin, or type of surgery. There was no significant difference in major postoperative complications. The pattern of the hemodilution curves was similar in patients operated with mini-circuit and off-pump technique (P > 005). Mini-circuit led to a 3.1 ± 11.9% hemoglobin reduction, which was similar to the off-pump group (1.6 ± 8.9%, P = 0.99 at ANOVA) and significantly different from the standard extracorporeal circuit group (16.0 ± 10.3%, P < 0.001 at ANOVA). The generalized linear mixed model determined that the standard circuit was the only independent predictor for increased hemodilution. Its effect on hemodilution was time-dependent and the slope of the hemoglobin curve was more pronounced between systemic heparinization and the end of surgery. Perioperative hemoglobin trends of patients who underwent myocardial revascularization with mini-circuit were similar to those of off-pump surgery and significantly less pronounced than those of standard extracorporeal circulation.

Bronchial malondialdehyde DNA adducts, tobacco smoking, and lung cancer.

Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)-DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA-DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA-DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01-2.26). MDA-DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16-2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA-DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04-2.20) and 1.45 (1.02-2.07)). Lung cancer cases with levels of MDA-DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65-9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency.

Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations.

The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.

Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure.

Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.