The association of prevalent medial meniscal pathology with cartilage loss in the medial tibiofemoral compartment over a 2-year period

Objective: To investigate the association of different types of magnetic resonance imaging (MRI)-detected medial meniscal pathology with subregional cartilage loss in the medial tibiofemoral compartment. Methods: A total of 152 women aged >= 40 years, with and without knee osteoarthritis (OA) were included in a longitudinal 24-month observational study. Spoiled gradient recalled acquisitions at steady state (SPGR) and T2-weighted fat-suppressed MRI sequences were acquired. Medial meniscal status of the anterior horn (AH), body, and posterior horn (PH) was graded at baseline: 0 (normal), 1 (intrasubstance meniscal signal changes), 2 (single tears), and 3 (complex tears/maceration). Cartilage segmentation was performed at baseline and 24-month follow-up in various tibiofemoral subregions using computation software. Multiple linear regression models were applied for the analysis with cartilage loss as the outcome. In a first model, the results were adjusted for age and body mass index (BMI). In a second model, the results were adjusted for age, BMI and medial meniscal extrusion. Results: After adjusting for age, BMI, and medial meniscal extrusion, cartilage loss in the total medial tibia (MT) (0.04 mm, P=0.04) and the external medial tibia (eMT) (0.068 mm, P=0.04) increased significantly for compartments with grade 3 lesions. Cartilage loss in the total central medial femoral condyle (cMF) (0.071 mm, P=0.03) also increased significantly for compartments with grade 2 lesions. Cartilage loss at the eMT was significantly related to tears of the PH (0.074 mm; P=0.03). Cartilage loss was not significantly increased for compartments with grade 1 lesions. Conclusion: The protective function of the meniscus appears to be preserved in the presence of intrasubstance meniscal signal changes. Prevalent single tears and meniscal maceration were found to be associated with increased cartilage loss in the same compartment, especially at the PH. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia

Individual differences in drug efficacy or toxicity can be influenced by genetic factors. We investigated whether polymorphisms of pharmacogenes that interfere with metabolism of drugs used in conditioning regimen and graft-versus-host disease (GvHD) prophylaxis could be associated with outcomes after HLA-identical hematopoietic stem cell transplantation (HSCT). Pharmacogenes and their polymorphisms were studied in 107 donors and patients with leukemia receiving HSCT. Candidate genes were: P450 cytochrome family (CYP2B6), glutathione-S-transferase family (GST), multidrug-resistance gene, methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor (VDR). The end points studied were oral mucositis (OM), hemorrhagic cystitis (HC), toxicity and venoocclusive disease of the liver (VOD), GvHD, transplantation-related mortality (TRM) and survival. Multivariate analyses, using death as a competing event, were performed adjusting for clinical factors. Among other clinical and genetic factors, polymorphisms of CYP2B6 genes that interfere with cyclophosphamide metabolism were associated with OM (recipient CYP2B6*4; P=0.0067), HC (recipient CYP2B6*2; P=0.03) and VOD (donor CYP2B6*6; P=0.03). Recipient MTHFR polymorphisms (C677T) were associated with acute GvHD (P=0.03), and recipient VDR TaqI with TRM and overall survival (P=0.006 and P=0.04, respectively). Genetic factors that interfere with drug metabolisms are associated with treatment-related toxicities, GvHD and survival after HLA-identical HSCT in patients with leukemia and should be investigated prospectively.

Validation of the National Institutes of Health Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: The Role of Cultural Adaptation and Structured Interviewing

Background: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. Methods: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. Results: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). Conclusion: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates. Copyright (C) 2008 S. Karger AG, Basel

Association of Dominant and Recessive Genes Confers Anthracnose Resistance in Stem and Leaves of Common Bean

Different genes might be involved in Colletotrichum lindemuthianum resistance in leaves and stem of common bean. This work aimed to study the genetic mechanisms of the resistance in the leaf and stem in segregating populations from backcrosses involving resistant cultivar AN 910408 and susceptible cultivar Ruda inoculated with spore suspensions of C. lindemuthianum race 83. Our results indicate that two genes which interact epistatically, one dominant and one recessive, are involved in the genetic control of leaf anthracnose resistance. As for stem anthracnose resistance, two genes also epistatic, one dominant and one recessive, explain the resistance to C. lindemuthianum race 83. The recessive gene is the same for leaf and stem resistance; however, the dominant genes are distinct and independent from each other. The three independent resistance genes of AN 910408 observed in this work could be derived from Guanajuato 31.

Genetic and environmental factors affecting ultrasound measures of longissimus muscle area and backfat thickness in Nelore cattle

The aim of the present study was to evaluate the genetic and environmental factors affecting records of longissimus muscle area (LMA) and back fat thickness (BF) obtained between the 12th and 13th ribs, and rump fat thickness (RF) between the hook and pin bones, measured by real-time ultrasound in Nelore cattle. Also, weight records of 22,778 animals born from 1998 to 2003, in ten farms across six Brazilian states were used. Carcass traits as measured by ultrasound of the live animal were recorded from 2002 to 2004 in 2590 males and females with ages varying from 450 to 599 days. Fixed models including farm, year and season of birth, sex and type of feed effects, and the covariates age of dam (AOD) and age of animal at measurement were used to study the effect of environmental factors on these traits. The genetic parameters for LMA, BF and RF were estimated with two and three-trait animal models with 120-day weights using a restricted maximum likelihood method. All environmental effects significantly affected carcass traits, with the exception of year of birth for BF and RF and AOD for LMA. The heritability estimates for LMA, BF and RF were 0.35, 0.51 and 0.39, respectively. Standard errors obtained in one-trait analyses were from 0.07 to 0.09. Genetic correlation estimates between LMA and the two traits of subcutaneous fat were low (close to zero) and 0.74 between BF and RF, indicating that the selection for LMA should not cause antagonism in the genetic improvement of subcutaneous fat measured by real-time ultrasound. (C) 2007 Elsevier B.V. All fights reserved.

Association of genetic variants in the adiponectin encoding gene (ADIPOQ) with type 2 diabetes in Japanese Brazilians

Aim: The objective of this study is to assess the contribution of ADIPOQ variants to type 2 diabetes in Japanese Brazilians. Methods: We genotyped 200 patients with diabetes mellitus (100 male and 100 female, aged 55.0 years [47.5-64.0 years]) and 200 control subjects with normal glucose tolerant (NGT) (72 male and 128 female, aged 52.0 years [43.5-64.5 years]). Results: Whereas each polymorphism studied (T45G, G276T, and A349G) was not significantly associated with type 2 diabetes mellitus, the haplotype GGA was overrepresented in our diabetic population (9.3% against 3.1% in NGT individuals, P=.0003). Also, this haplotype was associated with decreased levels of adiponectin. We also identified three mutations in exon 3: I164T, R221S, and H241P, but, owing to the low frequencies of them, associations with type 2 diabetes could not be evaluated. The subjects carrying the R221S mutation had plasma adiponectin levels lower than those without the mutation (2.10 mu g/ml [1.35-2.55 mu g/ml] vs. 6.68 mu g/ml [3.90-11.23 mu g/ml], P=.015). Similarly, the I164T mutation carriers had mean plasma adiponectin levels lower than those noncarriers (3.73 mu g/ml [3.10-4.35 mu g/ml] vs. 6.68 mu g/ml [3.90-11.23 mu g/ml]), but this difference was not significant (P=.17). Conclusions: We identified in the ADIPOQ gene a risk haplotype for type 2 diabetes in the Japanese Brazilian population. (C) 2010 Elsevier Inc. All rights reserved.

Transport of animals between rooms: A little-noted aspect of laboratory procedure that may interfere with memory

This study investigated the effects of transporting animals from the experimental room to the animal facility in between experimental sessions, a procedure routinely employed in experimental research, on long-term social recognition memory. By using the intruder-resident paradigm, independent groups of Wistar rats exposed to a 2-h encounter with an adult intruder were transported from the experimental room to the animal facility either 0.5 or 6h after the encounter. The following day, residents were exposed to a second encounter with either the same or a different (unfamiliar) intruder. Resident`s social and non-social behaviors were carefully scored and subjected to Principal Component Analysis, thus allowing to parcel out variance and relatedness among these behaviors. Resident rats transported 6h after the first encounter exhibited reduced amount of social investigation towards familiar intruders, but an increase of social investigation when exposed to a different intruder as compared to the first encounter. These effects revealed a consistent long-lasting (24h) social recognition memory in rats. In contrast, resident rats transported 0.5 h after the first encounter did not exhibit social recognition memory. These results indicate that this common, little-noted, laboratory procedure disturbs long-term social recognition memory. (C) 2011 Elsevier B.V. All rights reserved.

A Substrate Trapping Mutant Form of Striatal-Enriched Protein Tyrosine Phosphatase Prevents Amphetamine-Induced Stereotypies and Long-Term Potentiation in the Striatum

Background: Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods: A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and I hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results: Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. Conclusions: A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

Association of NAD(P)H Oxidase with Glucose-Induced Insulin Secretion by Pancreatic beta-Cells

We previously described the presence of nicotinamide adenine dinucleotide phosphate reduced form [NAD(P)H] oxidase components in pancreatic beta-cells and its activation by glucose, palmitic acid, and proinflammatory cytokines. In the present study, the importance of the NAD(P)H oxidase complex for pancreatic beta-cell function was examined. Rat pancreatic islets were incubated in the presence of glucose plus diphenyleneiodonium, a NAD(P)H oxidase inhibitor, for 1 h or with the antisense oligonucleotide for p47(PHOX) during 24 h. Reactive oxygen species (ROS) production was determined by a fluorescence assay using 2,7-dichlorodihydrofluorescein diacetate. Insulin secretion, intracellular calcium responses, [U-(14)C] glucose oxidation, and expression of glucose transporter-2, glucokinase and insulin genes were examined. Antisense oligonucleotide reduced p47(PHOX) expression [an important NAD(P)H oxidase cytosolic subunit] and similarly to diphenyleneiodonium also blunted the enzyme activity as indicated by reduction of ROS production. Suppression of NAD(P)H oxidase activity had an inhibitory effect on intracellular calcium responses to glucose and glucose-stimulated insulin secretion by isolated islets. NAD(P)H oxidase inhibition also reduced glucose oxidation and gene expression of glucose transporter-2 and glucokinase. These findings indicate that NAD(P)H oxidase activation plays an important role for ROS production by pancreatic beta-cells during glucose-stimulated insulin secretion. The importance of this enzyme complex for the beta-cell metabolism and the machinery involved in insulin secretion were also shown. (Endocrinology 150: 2197-2201, 2009)

Chronic action of association of zidovudine, lamivudine and ritonavir on pregnant rats. A biologic assay

Purpose: To evaluate at term the effects of a highly active antiretroviral (HAAR) drug association administered during the entire period of rat pregnancy. Methods: Three groups (n = 10 each) of adult pregnant rats were treated with an oral solution of HAAR (Exp 1 = 10/5/20 mg/kg b.w.; Exp 2 = 30/15/60 mg/kg b.w.; Exp 3 = 90/45/180 mg/kg b.w.) from day ""0"" up to the 20th day of pregnancy. A fourth group served as a control. At term (20th day) the rats were killed under deep anesthesia and the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. Results: The highest HAAR doses caused lower maternal weight gain, lower litter weights, and lower placental weights compared to the control group. Conclusions: HAAR during the entire period of rat pregnancy can reduce maternal body weight gain and lower term placental weight.

Association of complement factor H Y402H polymorphism and age-related macular degeneration in Brazilian patients

Purpose: The aim of this study was investigate the association between complement Factor H polymorphism (Y402H) and age-related macular degeneration (AMD) in Brazilian patients. Methods: Patients with AMD aged 50 or more and age-matched healthy controls were enrolled in the study. Genomic DNA was isolated from leucocytes of patients and controls; the Y402H polymorphism of complement Factor H gene (CFH) was determined by polymerase chain reaction directed sequencing. Results: The frequency of 1277C allele of Factor H was 56.30% in patients with AMD compared with 36.51% in controls (p-value = 0.001). The genotypic distribution differed significantly between the two groups (1277CC 36.98%, 1277CT 38.65% and 1277TT 24.37% for AMD group; 1277CC 13.16%, 1277CT 46.71% and 1277TT 40.13% for controls, p-value = 0.001). The odds ratio for patients with AMD carrying only one 1277C allele was 1.36 and for those carrying two 1277C alleles was 4.63, when compared to the control group. Conclusions: These results suggest the Y402H polymorphism of CFH is a risk factor to the development of AMD in Brazilian patients. This is in accordance with findings from the majority of previous study population in Europe and North American.

Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Background. Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. Methods. In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1 -seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1 -seronegative individuals (control group). Results. Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor a and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1 beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. Conclusions. HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.