Parkinson's disease and CYP2D6 polymorphism in Asian populations: A meta-analysis

Polymorphism of CYP2D6 and its relationship with the development of Parkinson's disease (PD) has been controversial. The distribution of the B-mutation of CYP2D6, a mutation that results in the absence of a functional protein, differs by ethnicity and accounts for less than 1% of the 'poor metabolizer' phenotype in Asians. Thus, a meta-analysis was conducted to determine if polymorphism, other than the B-mutation, within the CYP2D6 gene confers a greater susceptibility to PD outcome among Asian populations. Eleven studies were identified, two of which were excluded due to unavailability in the English language or availability of the same original data in more detail in another publication. None of the studies showed a statistically significant association between CYP2D6 polymorphism and PD (p<0.05). The overall odds ratio was 0.84 (95% confidence interval 0.66-1.08). We conclude that among Asian populations, there is no convincing evidence of an association between CYP2D6 polymorphism and the risk of developing PD.     

Polymicrogyria and absence of pineal gland due to PAX6 mutation

Identification of genes involved in human cerebral development is important for our understanding of disorders with potential neurodevelopmental causes such as epilepsy and learning disability. Murine models suggest that PAX6 plays a key role in human brain development. With magnetic resonance imaging in 24 humans heterozygous for defined PAX6 mutations, we demonstrated widespread structural abnormalities including absence of the pineal gland and unilateral polymicrogyria.     

Lifetime antecedents of cognitive reserve

We used path analysis on data from the British 1946 birth cohort to model lifetime antecedents of cognitive reserve, represented by the NART at 53 years, and compared this model for verbal memory and psychomotor function at this age, cognitive outcomes that are sensitive to age-associated decline. We showed independent paths from childhood cognition, educational attainment and adult occupation to cognitive reserve, with that from childhood cognition the strongest, and that from adult occupation the weakest. A similar pattern was found for the verbal memory and psychomotor outcomes, although the pathways were weaker than those to the NART. The pattern was also mirrored by the paths from paternal occupation to childhood cognition, educational attainment and adult occupation, with that to childhood cognition the strongest, and that to adult occupation the weakest. The direct influence of paternal occupation on cognitive reserve was negligible, and almost entirely mediated by childhood cognitive ability and educational attainment.     

Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes

OBJECTIVE: Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial. RESEARCH DESIGN AND METHODS: A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18-45 years and not treated with permanent insulin for < or =6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1 alpha (HNF-1 alpha) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1 alpha gene. RESULTS: A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a beta-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1 alpha mutations, the novel missense mutation A501T, and the previously reported R583Q. CONCLUSIONS: This unselected series shows that there is considerable heterogeneity in apparent YT2D. beta-Cell autoantibodies should be performed in all those presenting at ages 18-45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.     

Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study

BACKGROUND: It has been hypothesized that n-3 polyunsaturated fatty acids (PUFAs) are involved in mood regulation, but epidemiologic evidence for such a link in the general population is lacking. OBJECTIVE: This study examined whether community-dwelling elderly persons with depression have a fatty acid composition that is different from that of nondepressed persons. DESIGN: We screened 3884 adults aged > or = 60 y for depressive symptoms as part of the Rotterdam Study. Subjects who screened positive had a psychiatric interview to diagnose depressive disorders. All eligible subjects had their blood drawn for measurement of plasma phospholipid concentrations. We compared percentages of n-3 and n-6 PUFAs and their ratios between 264 subjects with depressive symptoms, including 106 subjects with depressive disorders, and 461 randomly selected reference subjects. We also investigated whether atherosclerosis or the inflammatory response as measured by C-reactive protein underlies the relation between fatty acid composition and depression. RESULTS: Subjects with depressive disorders had a higher ratio of n-6 to n-3 PUFAs, but differences in individual PUFAs were mostly small. However, depressed subjects with normal CRP concentrations (< 1.5 mg/L) had a substantially altered fatty acid composition; percentages of n-3 PUFAs and ratios of n-6 to n-3 PUFAs were significantly lower and higher, respectively, in subjects with depressive disorders than in control subjects [5.2% compared with 5.9% (P = 0.02) and 7.2 compared with 6.6 (P = 0.01), respectively]. This relation was not due to atherosclerosis. CONCLUSIONS: In community-dwelling persons, fatty acid composition is related to depression. Because this relation was not secondary to inflammation, atherosclerosis, or possible confounders, it suggests a direct effect of fatty acid composition on mood.     

Symptoms of Posttraumatic Stress Disorder in a New Orleans Workforce Following Hurricane Katrina

On August 29, 2005, Hurricane Katrina made landfall resulting in catastrophic damage and flooding to New Orleans, LA, and the Gulf Coast, which may have had significant mental health effects on the population. To determine rates and predictors of symptoms consistent with a diagnosis of posttraumatic stress disorder (PTSD) in New Orleans residents following Hurricane Katrina, we conducted a web-based survey 6 months after Hurricane Katrina made landfall. Participants included 1,542 employees from the largest employer in New Orleans. The prevalence of PTSD symptoms was 19.2%. Predictors of PTSD symptoms in a multivariate-adjusted regression model included female sex, non-black race, knowing someone who died in the storm, not having property insurance, having had a longer evacuation, a much longer work commute compared to before Hurricane Katrina, and currently living in a newly purchased or rented house or in a temporary trailer. Despite universal health coverage and the benefits of an employee assistance program for all employees, only 28.5% of those with PTSD symptoms had talked to a health professional about the events of Hurricane Katrina or issues encountered since the storm. A significant burden of PTSD symptoms was present 6 months following Hurricane Katrina among a large group of adults who had returned to work in New Orleans. Given their key role in the economic redevelopment of the region, there is a tremendous need to identify those in the workforce with symptoms consistent with PTSD and to enhance treatment options. The strong relationship between displacement from ones’ pre-Katrina residence and symptoms of PTSD suggests a need to focus resource utilization and interventions on individuals living in temporary housing. DeSalvo, Tynes, and Muntner are with the Section of General Internal Medicine and Geriatrics, Tulane University School of Medicine, New Orleans, LA, USA; DeSalvo, Hyre, Menke, and Muntner are with the Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Ompad is with the Center of Urban Epidemiologic Studies, New York Academy of Medicine, New York, NY, USA; Tynes is with the Department of Psychiatry, Tulane University School of Medicine, New Orleans, LA, USA; Tynes is with the Jefferson Parish Human Services Authority, Metairie, LA, USA.     

A comparative study of the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 in Plasmodium falciparum and P. vivax.

We investigated the genetic diversity of the 42kDa fragment of the merozoite surface protein 1 (MSP-1) antigen in Plasmodium falciparum and P. vivax, as well as in non-human primate malarial parasites. This fragment undergoes a proteolytic cleavage generating two fragments of 19kDa (MSP-1(19)) and 33kDa (MSP-1(33)) that are critical in erythrocyte invasion. We found that overall the MSP-1(33) fragment exhibits greater genetic diversity than the MSP-1(19) regardless of the species. We have found evidence for positive natural selection only in the human malaria parasites by comparing the rate of non-synonymous versus synonymous substitutions. In addition, we found clear differences between the two major human malaria parasites. In the case of P. falciparum, positive natural selection is acting on the MSP-1(19) region while the MSP-1(33) is neutral or under purifying selection. The opposite pattern was observed in P. vivax. Our results suggest different roles of this antigen in the host-parasite immune interaction in each of the major human malarial parasites.     

Anti-idiotype CEA antibody vaccine breaks immune tolerance

Cytokine-targeted therapies, the first developed being infliximab, may lower the overall cost of Crohn’s disease by improving outcomes and reducing the need for medical interventions. Dr Russell Cohen from the University of Chicago, US, made this statement at a symposium at the 33rd annual meeting of the American Society of Health-System Pharmacists [ Las Vegas, US; December 1998 ]. During the symposium, Dr Cohen and other experts discussed the pathology and management of Crohn’s disease.     

大麻酚类受体拮抗剂SR141716A减少乙醇蒸气室中大鼠的自发反应性乙醇自身给药行为(英文)

AIM: To study the potential role of dependence statuson CB_1-mediated blockade of ethanol self-administra-tion. METHODS: We examined the effects of thecannabinoid antagonist SR141716A (0, 0.03, 0.3,and 3 mg/kg) on pperant ethanol (10 ％ v/v) self-administration in male Wistar rats that were madeethanol-dependent by chronic (14 d ) exposure toethanol vapor-chambers or exposed to air in identicalvapor chambers.RESULTS: Dependent animalsresponded more for ethanol than did air controlnondependent tats. The acute administration of a 3mg/kg dose of SR141716A almost suppressed ethanolself-administration ouly in ethanol dependent animals.