Comparison of lipopolysaccharides from Bacteroides, Porphyromonas, Prevotella, Campylobacter and Wolinella spp. by Tricine-SDS-PAGE

Abstract Lipopolysaccharides (LPSs) of 11 bacterial strains from the type species of the genera Bacteroides (B, fragilis), Prevotella (Pr. melaninogenica), Porphyromonas (Po. gingivalis), Canmpylobacter (C. fetus subsp. fetus), and Wolinella (W. succinogens), and from the type strains of B. distasonis, B. forythus, B. ureolyticus, Po. levii, Po. macacae, and C. gracilis, were extracted with hot water-phenol (Westphal method). S-form LPSs, obtained from all organisms, were well resolved with tricine-sodium-dodecyl-sulphate polyacrylamide gel electrophoresis and visualized by silver staining. Lipid A was not stained. Also profiles from LPS of Escherichia coli, serotypes 0111:B4 and 055:B5, could be distinguished. While W. succinogenes showed a relatively short S-form LPS on electrophoregrams, the other bacteria, including B. fragilis, exhibited long-ladder LPSs. Po. gingivalis displayed the largest number of bands and the longest O-chain. The long O-chain of this bacterium may be important for its virulence.     

Genome-wide association of mood-incongruent psychotic bipolar disorder

Mood-incongruent psychotic features (MICP) are familial symptoms of bipolar disorder (BP) that also occur in schizophrenia (SZ), and may represent manifestations of shared etiology between the major psychoses. In this study we have analyzed three large samples of BP with imputed genome-wide association data and have performed a meta-analysis of 2196 cases with MICP and 8148 controls. We found several regions with suggestive evidence of association (P<10^–6), although no marker met genome-wide significance criteria. The top associations were on chromosomes: 6q14.2 within the PRSS35/SNAP91 gene complex (rs1171113, P=9.67 × 10^–8); 3p22.2 downstream of TRANK/LBA1 (rs9834970, P=9.71 × 10^–8); and 14q24.2 in an intron of NUMB (rs2333194, P=7.03 × 10^–7). These associations were present in all three samples, and both rs1171113 and rs2333194 were found to be overrepresented in an analysis of MICP cases compared with all other BP cases. To test the relationship of MICP with SZ, we performed polygenic analysis using the Psychiatric GWAS Consortium SZ results and found evidence of association between SZ polygenes and the presence of MICP in BP cases (meta-analysis P=0.003). In summary, our analysis of the MICP phenotype in BP has provided suggestive evidence for association of common variants in several genes expressed in the nervous system. The results of our polygenic analysis provides support for a modest degree of genetic overlap between BP with MICP and SZ, highlighting that phenotypic correlations across syndromes may be due to the influence of polygenic risk factors.     

The Persian Wednesday Eve Festival "Charshanbe-Soori" fireworks eye injuries: a case series

PURPOSE: To describe the clinical spectrum and severity of eye injuries sustained during the Persian Wednesday Eve Festival "Charshanbe-Soori" and to identify the fireworks devices involved. METHODS: Prospectively, consecutive patients treated for fireworks-related eye injuries in the emergency room at Farabi Eye Hospital, Tehran, over 3 days around the occasion in 2000, 2001, and 2002 were studied. RESULTS: Four hundred thirty-seven cases of eye injuries with an age range of 2-74 (median 17; SD 11.1) years were studied: 84.6% were male; 18.6% of the injuries were bilateral; 79.9% of the injured were bystanders or passersby. Eleven types of devices were involved, of which seven were explosives and eight were homemade. "Narenjaks," homemade grenades, were involved in 62.2%, firecrackers in 14.8%, and sparklers in 6.2% of the events. Injuries were categorized as severe in 49% of cases, and 45 (10.4%) people were hospitalized. Five eyes with no light perception and/or enucleation, 33 cases of monocular blindness, 54 (12.3%) cases of open globe (including intraocular foreign bodies) were observed. Grenades, bystander and passerby roles, outdoor context, a relatively older age, lower socioeconomic status, and male gender in the subset of passive roles were the determinants of more severe injuries (all p values < 0.05). Lid injuries (67.7%), corneal abrasions (51.6%), hyphema (48.1%), superficial foreign bodies (32.5%), and corneal contusions (13.8%) were the five leading injuries. CONCLUSIONS: In Iran, fireworks cause frequent and diverse injuries during the Wednesday Eve Festival and are a leading cause of severe eye injuries and monocular blindness.     

APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study

Asymptomatic Alzheimer''s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.     

Emg detection of loss of consciousness during a standardized IV induction

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Hepatoprotective effect of the hydroalcoholic extract of Cichorium intybus in a rat model of obstructive cholestasis

Background and study aimsObstructive cholestasis increases the levels of oxidants and inflammatory mediators, leading to liver damage. Previous studies have found that Cichorium intybus possesses anti-inflammatory effects. In the present study, the effects of the hydroalcoholic extract of C. intybus leaves were assessed in a rat model of obstructive cholestasis.Material and methodsMale Wistar rats were randomly divided into five groups (n = 6 rats per group): sham-operated, control [bile duct ligation (BDL) + vehicle)] and BDL + extract treatment (100, 200 and 400 mg/kg/day, i.p.) groups. Rats received treatments for 7 consecutive days. On the eighth day, prothrombin time (PT); serum albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and total and direct bilirubin levels and total antioxidant and paraoxonase activities were measured using colorimetric methods. In addition, tumour necrosis factor-α and nitric oxide (NO) levels were measured using enzyme-linked immunosorbent assay.ResultsThe hydroalcoholic extract of C. intybus significantly decreased PT and the serum levels of AST, ALT, TNF-α and NO compared with the control group (p < 0.05). On the other hand, the serum albumin levels were increased in the extract-treated groups compared with the control group (p < 0.05).ConclusionThe hydroalcoholic extract of C. intybus protects the liver against injury induced by obstructive cholestasis.     

Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33

OBJECTIVE: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. METHOD: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. RESULTS: Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. CONCLUSIONS: Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.     

Developing new treatments for Alzheimer's disease: the who, what, when, and how of biomarker-guided therapies

ABSTRACTThis synthetic review presents an approach to the use of biomarkers for the development of new treatments for Alzheimer's disease (AD). After reviewing the process of translation as applied to AD, the paper provides a general update on what is known about the biology of the disease, and highlights currently available treatments. This is followed by a discussion of future drug development for AD emphasizing the roles that biomarkers are likely to play in this process: (1) define patients who are going to progress rapidly for the purpose of trial enrichment; (2) differentiate disease and therapeutically relevant AD subtypes; (3) assess the potential activity of specific therapies in vivo or ex vivo; and (4) measure the underlying disease state, so as to (a) detect disease and assess drug response in asymptomatic patients, (b) serve as a secondary outcome measure in clinical trials of symptomatic patients, and (c) decide if further development of a treatment should be stopped if not likely to be effective. Several examples are used to illustrate each biomarker utility in the AD context.     

Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical covariates

Despite compelling evidence that genetic factors contribute to bipolar disorder (BP), attempts to identify susceptibility genes have met with limited success. This may be due to the genetic heterogeneity of the disorder. We sought to identify susceptibility loci for BP in a genome-wide linkage scan with and without clinical covariates that might reflect the underlying heterogeneity of the disorder. We genotyped 428 subjects in 98 BP families at the Center for Inherited Disease Research with 402 microsatellite markers. We first carried out a non-parametric linkage analysis with MERLIN, and then reanalyzed the data with LODPAL to incorporate clinical covariates for age at onset (AAO), psychosis and comorbid anxiety. We sought to further examine the top findings in the covariate analysis in an independent sample of 64 previously collected BP families. In the non-parametric linkage analysis, three loci were nominally significant under a narrow diagnostic model and seven other loci were nominally significant under a broader model. The top findings were on chromosomes 2q24 and 3q28. The covariate analyses yielded additional evidence for linkage on 3q28 with AAO in the primary and independent samples. Although none of the linked loci were genome-wide significant, their congruence with prior results and, for the covariate analyses, their identification in two separate samples increases the likelihood that they are true positives and deserve further investigation. These findings further demonstrate the value of considering clinical features that may reflect the underlying heterogeneity of disease in order to facilitate gene mapping.