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An electrochemical sensor has been developed for the determination of the herbicide bentazone, based on a GC electrode modified by a combination of multiwalled carbon nanotubes (MWCNT) with β-cyclodextrin (β-CD) incorporated in a polyaniline film. The results indicate that the β-CD/MWCNT modified GC electrode exhibits efficient electrocatalytic oxidation of bentazone with high sensitivity and stability. A cyclic voltammetric method to determine bentazone in phosphate buffer solution at pH 6.0, was developed, without any previous extraction, clean-up, or derivatization steps, in the range of 10-80 µmol L−1, with a detection limit of 1.6 µmol L−1 in water. The results were compared with those obtained by an established HPLC technique. No statistically significant differences being found between both methods. [ABSTRACT FROM AUTHOR]

Summary A case of a type I rectal atresia (also known as membranous rectal atresia) in a newborn donkey is reported. Clinical examination, survey radiographs and barium enema radiographs suggested rectal atresia. An exploratory laparotomy was performed; however, surgical correction of the defect was not possible due to the narrow pelvic cavity. Euthanasia was performed. At necropsy, it was possible to observe a fibrous cord connecting the small colon to a residual rectal ampulla, which opened to a normal anus. The radiographic and anatomical characteristics enabled the classification of the defect as type I rectal atresia, which is a rare congenital anomaly that is difficult to correct through surgery. This report contributes to the study of rectal atresia in newborn equids, alerts for the occurrence in donkeys and is, to our knowledge, the first to be reported in this species in Brazil. [ABSTRACT FROM AUTHOR]

Background Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation. Aim To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury. Methods Retrospective description of 31 patients (14 Crohn’s, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy. Results Mean AZA dose was 2.2 ± 0.4 mg·kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1–5.2). The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7–5.2), the therapy was switched to MP at a mean dose of 1.3 ± 0.2 mg·kg/day. Median of follow-up of MP therapy was 32 months (8–54). In 87.1% of patients (95%CI: 70–96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3–29%), liver injury reappeared (two cholestasis, two mixed), 1–3 months after the onset of MP exposure. Conclusion The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor alpha (TNF-α) and adiponectin are strongly related to insulin sensitivity; insulin resistance of pregnancy is a major determinant of infant's birthweight. We aimed to study the contributions of maternal serum concentrations of soluble TNF-α receptors (sTNFR1 and sTNFR2) and adiponectin to infant's birthweight.Cross-sectional, hospital-based study of insulin sensitivity during gestation.Fifty-one healthy women with uncomplicated pregnancy and delivery (except for elective Caesarian section) and their healthy newborn infants.Maternal blood levels of glucose, insulin, glycosylated haemaglobin (HbA1c), sTNFR1, sTNFR2 and adiponectin at delivery; cord-blood levels of sTNFR1, sTNFR2 and adiponectin.At delivery, maternal sTNFR2 correlated with systolic blood pressure (SBP;r = 0·38,P = 0·005). In multiple regression analyses, SBP and HbA1c were independent predictors of sTNFR2, explaining 18 and 7% of its variance, respectively; insulin resistance index (HOMA-IR), body mass index at delivery and SBP were independent predictors of adiponectin, explaining 15, 8 and 7% of its variance, respectively. Both maternal sTNFR2 and SBP were negatively correlated with infant's birthweight (r = −0·28,P = 0·04 andr = −0·36,P = 0·01 respectively, adjusted for sex and gestational age). In multivariate regression analyses, infant's sex and either maternal sTNFR2 or adiponectin were independent predictors of infant's birthweight, each explaining between 6 and 9% of birthweight variance. Further addition of maternal SBP to these models revealed that this variable was the main predictor of infant's birthweight, explaining 13% of its variance.Maternal sTNFR2 and adiponectin are independently related to both maternal blood pressure and infant's birthweight in uncomplicated pregnancy. The contributions of the TNF-α system and adiponectin to hypertensive disorders of pregnancy and fetal growth merit further studies. [ABSTRACT FROM AUTHOR]

The present work analyzes by light microscopy circulating blood cells and lymphoid organs of the caecilian, Ichthyophis kohtaoensis. Peripheral blood contains erythrocytes, thrombocytes, lymphocytes, monocytes, heterophils, easinophils and basophils. Thymus, liver and spleen are the major lymphomyeloid organs in this caecilian and there is not a haemopoietic functioning bone marrow. The results are discussed on the basis of the possible phylogenetic positions of the Apoda emphasizing their relationships to the Urodela. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning unusual acquired dermal melanocytosis on the trunk.

Studies the tolerance of celecoxib, a high affinity COX-2 inhibitor in 20 patients suffering urticaria and/or angioedema (U/AE) associated with nonsteroidal antiinflammatory drugs (NSAIDs). Basis of the diagnosis used for the patients; Use of exclusion criteria; Constituents of the oral provocation testing being used; Type of tests that were conducted on different days; Basis on which the test was accepted to be positive.

Presents a study which determined the tolerance of rofecoxib in patients suffering urticaria and angioedema associated with nonsteroidal anti-inflammatory drugs (NSAID). Criteria used in selecting the patients for the study; Information on the challenge protocol performed during the study; Clinical findings in NSAID-intolerant patients who tolerated rofecoxib.

Background: Diabetes mellitus (DM) has been associated with salivary disorders such as xerostomia and hyposalivation. The aim of this study was to determine the prevalence of these disorders and their risk factors in DM patients., Methods: DM patients from two health centers were included. Epidemiological and DM control-related variables were collected. Xerostomia Inventory was filled out by the patients and unstimulated whole salivary flow was collected. Logistic regression tests were performed., Results: A total of 168 patients were included (46.4% men, 53.6% women, mean age 72.54 [SD 11.03 years]). Thirteen patients had Type 1 DM and 155 had Type 2 DM. 52.4% experienced xerostomia and 41.1% had unstimulated whole salivary flow hyposalivation. Women were more likely to suffer hyposalivation than men (OR 2.5, 95% CI 1.32-4.73; p = 0.005). Patients with T2DM were less likely to suffer UWS hyposalivation than T1DM patients (OR 0.28, 95% CI 0.08-0.95; p = 0.04). Glycemic control was not significantly worse in patients with xerostomia and hyposalivation. The drugs for the treatment of DM were not associated with salivary disorders. However, some drugs to treat other comorbidities such hypertension and neurological diseases were associated with xerostomia and hyposalivation., Conclusions: The prevalence of xerostomia and unstimulated whole salivary flow hyposalivation in patients with DM is high. Female sex, T1DM, and the use of certain non-antidiabetic drugs increased the risk of suffering these disorders. The possible association between DM, xerostomia, and/or hyposalivation is complex and may be influenced by multiple factors. Therefore, further studies are needed to evaluate whether DM influences these salivary disorders., (© 2024 The Author(s). Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Background: Brain microvascular endothelial cells form a highly selective blood brain barrier regulated by the endothelial tight junctions. Cerebral ischemia selectively targets tight junction protein complexes, which leads to significant damage to cerebral microvasculature. Short noncoding molecules called microRNAs are implicated in the regulation of various pathological states, including endothelial barrier dysfunction. In the present study, we investigated the influence of microRNA-155 (miR-155) on the barrier characteristics of human primary brain microvascular endothelial cells (HBMECs)., Methods and Results: Oxygen-glucose deprivation was used as an in vitro model of ischemic stroke. HBMECs were subjected to 3 hours of oxygen-glucose deprivation, followed by transfections with miR-155 inhibitor, mimic, or appropriate control oligonucleotides. Intact normoxia control HBMECs and 4 oxygen-glucose deprivation-treated groups of cells transfected with appropriate nucleotide were subjected to endothelial monolayer electrical resistance and permeability assays, cell viability assay, assessment of NO and human cytokine/chemokine release, immunofluorescence microscopy, Western blot, and polymerase chain reaction analyses. Assessment of endothelial resistance and permeability demonstrated that miR-155 inhibition improved HBMECs monolayer integrity. In addition, miR-155 inhibition significantly increased the levels of major tight junction proteins claudin-1 and zonula occludens protein-1, while its overexpression reduced these levels. Immunoprecipitation and colocalization analyses detected that miR-155 inhibition supported the association between zonula occludens protein-1 and claudin-1 and their stabilization at the HBMEC membrane. Luciferase reporter assay verified that claudin-1 is directly targeted by miR-155., Conclusions: Based on these results, we conclude that miR-155 inhibition-induced strengthening of endothelial tight junctions after oxygen-glucose deprivation is mediated via its direct target protein claudin-1., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Rubinstein-Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8-10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype-phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Costimulatory receptor CD226 plays an important role in T cell activation, differentiation, and cytotoxicity. This study was undertaken to investigate the genetic association of CD226 with susceptibility to systemic lupus erythematosus (SLE) and to assess the functional implications of this association., Methods: Twelve tag single-nucleotide polymorphisms (SNPs) in CD226 were typed in 1,163 SLE patients and 1,482 healthy control subjects from Europe or of European ancestry. Analyses of association were performed by single-marker Cochran-Mantel-Haenszel meta-analysis, followed by haplotype analysis. Gene expression was analyzed by quantitative real-time polymerase chain reaction analyses of RNA from peripheral blood mononuclear cells, and by fluorescence-activated cell sorter analysis. To study the functional impact of the associated variants, luciferase reporter constructs containing different portions of the 3'-untranslated region (3'-UTR) of the gene were prepared and used in transfection experiments., Results: A 3-variant haplotype, rs763361;rs34794968;rs727088 (ATC), in the last exon of CD226 was associated with SLE (P = 1.3 × 10(-4) , odds ratio 1.24, 95% confidence interval 1.11-1.38). This risk haplotype correlated with low CD226 transcript expression and low CD226 protein levels on the surface of CD4+ and CD8+ T cells and natural killer T (NKT) cells. NK cells expressed high levels of CD226, but this expression was independent of the haplotype. Reporter assays with deletion constructs indicated that only the presence of rs727088 could account for the differences in the levels of luciferase transcripts., Conclusion: This study identified an association of CD226 with SLE in individuals of European ancestry. These data support the importance of the 3'-UTR SNP rs727088 in the regulation of CD226 transcription both in T cells and in NKT cells., (Copyright © 2010 by the American College of Rheumatology.)

Dopaminergic dysfunction in the prefrontal cortex (PFC) is involved in the pathophysiology of schizophrenia. In the PFC, dopamine signalling largely depends on the D1 receptors, which are coded by the DRD1 gene, and on the regulation of dopamine levels by the enzyme catechol-O-methyltransferase (COMT). Here, we investigate the role of DRD1 and its interaction with the COMT gene in schizophrenic patients. In two gender-limited independent patient and control samples, we genotype five Tag single nucleotide polymorphisms (tagSNPs) of DRD1. The DRD1 SNP and haplotype associations, as well as interaction effects with the Val158Met COMT SNP were analyzed. In the male sample, we found the rs11746641 and rs11749676 DRD1 SNPs were associated with schizophrenia. Haplotype analyses identified the T-A-T-C-T variant related to a protective effect (P = 0.008) and the G-G-T-C-C variant that showed a tendency to be a risk factor for the disorder (P = 0.012). A logistic regression analysis revealed a significant pattern of interaction between DRD1 and COMT for both the rs11746641 (P = 0.002) and rs11749676 (P = 4.5 x 10(-5)) SNPs. DRD1-associated haplotypes were exclusively related to schizophrenia in the Val homozygous subgroup of patients (T-A-T-C-T: P = 0.003; G-G-T-C-C: P = 0.006). In females, none of the DRD1 SNPs were linked to the disorder. Our genetic data suggest that DRD1 and COMT are epistatically associated with protection against and the risk of developing schizophrenia in a gender-dependent fashion, and support the role of dopamine dysfunction at the PFC in the pathophysiology of this disorder.

The functional Val158Met polymorphism (rs4680) located at the gene that codes for the catechol-O-methyltransferase (COMT) has been extensively investigated in schizophrenia although current data are still controversial. Since COMT activity is sexually dimorphic, we carried out two independent studies in homogeneous samples of male and female Spanish schizophrenic patients. In males, we found an association between the homozygous Val genotype and the disorder, which resembled a recessive model (P = 0.022; odds ratio [OR] = 1.67). This Val homozygotes overrepresentation is produced at the expense of the heterozygous individuals decrease, whilst the Met homozygotes showed no differences when compared controls and patients. As a consequence, the heterozygous genotype in this sample had a protective effect (P = 0.03; OR = 0.65) and a strong deviation from Hardy-Weinberg equilibrium in male cases was observed (P = 0.006). In addition, a 2-SNP haplotype analysis (rs4818-Val158Met) confirmed there is an overrepresentation of the different homozygous Val genotypes in the male schizophrenic sample. Regarding females, we did not find any statistically significant association between COMT SNP and schizophrenia. In the light of this we suggest that the Val158Met SNP is involved in risk and protective genotypes for the vulnerability to schizophrenia in Spanish male population., ((c) 2009 Wiley-Liss, Inc.)

Although we are far from a universally accepted pattern of impaired function at altitude, there is evidence indicating motor, perceptual, memory and behavioural deficits in adults. Even relatively low altitudes (2500 m) may delay reaction time, and impair motor function. Extreme altitude exposure (>5000 m) may result in more pronounced impairment that can persist after returning to the lowlands. Research into the effects of altitude exposure earlier in development is lacking by comparison. Un-acclimatized children can suffer from acute mountain sickness, and, in native populations born at altitude, subtle cognitive and behavioural deficits suggest incomplete adaptation to hypoxia. The study of neurobehavioural functioning at altitude may provide important information about the effects of clinical hypoxia on the human brain and behavioural development.

Objective: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors., Methods: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method., Results: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome., Conclusion: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.