Th-1 cytokines gene polymorphism in human brucellosis

Brucellosis is a worldwide zoonosis. Infection with Brucella species results in the activation of cell-mediated immune response. The interaction between Th1and Th2 cytokines determines the outcome of disease. Production of each cytokine is in turn affected by genetic factors. In this study, we investigated the possible association between Th1 cytokines gene polymorphism and brucellosis. Different genotypes of TNF-alpha, IFN-gamma and IL-2 were determined by polymerase chain reaction-sequence-specific primer in 47 patients with brucellosis and in 166 healthy controls. Allele frequencies of these genotypes were compared using the chi2 test. The results showed a significant difference in the TNF-alpha genotype GG/GG in patients in comparison with controls (76.7% vs. 21%) (P = 0.001, OR = 12.42, 95%CI 5.7-27.7). There was no significant difference in the frequency distribution of the IFN-gamma genotypes between two groups. IL-2 GG genotype at position -330 was about two times more common in cases than in controls, but the difference was not significant (10.6 vs. 4.6 P value = 0.09). This study shows that genetically low producers of TNF-alpha are possibly susceptible to brucellosis and raise doubt about the role of gene polymorphism of INF-gamma in brucellosis which was demonstrated in previous studies. It seems that patients with brucellosis did not have a defect in producing IL-2 with even a trend towards producing higher amounts of this cytokine.     

In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties

Background and purpose:

The histamine H₄ receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H₄ receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine).

Experimental approach:

We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H₄ receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis.

Key results:

A-940894 potently binds to both human and rat histamine H₄ receptors and exhibits considerably lower affinity for the human histamine H₁, H₂ or H₃ receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D₂ levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice.

Conclusions and Implications:

These data suggest that A-940894 is a potent and selective histamine H₄ receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H₄ receptor pharmacology.     

Plasma total homocysteine （THCY） level and other biochemical risk factors in hypertensives with and without cardiovascular events

Objective： The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive. Methods： Thirty-six hypertensive patients were recruited with 36 age and sex-matched controls. The age, sex and anthropometric measurements including height, weight and body mass index （BMI） were taken. Plasma total cholesterol, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, triglycerides and tHcy were analyzed. The results of the two groups were compared. Results： The mean total cholesterol and LDL- C were significantly higher in the subjects than in the controls （P = 0.01 and 0.03 respectively）. On the other hand, means of HDL-C and triglycerides were not significantly different between the two groups （P =0.06 and 0.68 respectively）. Mean total plasma tHcy was （ 12.95 ±4.9） μmol/L in hypertensive patients when compared with （ 11.29 ±3.6） μmol/L in the controls （P = 0.09） , however the mean tHcy was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications （one way Anova F = 3.63, P = 0.04）. Significant positive correlation was seen between tHcy and systolic blood pressure, diastolic blood pressure, BMI and LDL-C. Conclusion ： The study suggests that elevated plasma tHcy may predict occurrence of cardiovascular complications in hypertensive individuals.     

IL-2, IFN-γ, and IL-12 Gene Polymorphisms and Susceptibility to Multiple Sclerosis

Background  

Multiple sclerosis (MS) is a multifactorial disease. Positive genetic background could predispose individuals to this chronic disabling disease. In order to investigate the role of some proinflammatory cytokines (interleukin (IL)-2, IL-12, and interferon-gamma (IFN-γ)) as a risk factor for MS, this study was performed.     

PLUNC protein expression in major salivary glands of HIV‐infected patients

Oral Diseases (2011) 17 , 258–264 Objective: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. Methods: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non‐specific sialadenitis, and 30 HIV‐negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV‐negative group was performed. Results: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV‐negative cases. Conclusions: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non‐HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.     

Reconstruction of bladder and urethra using ileocecal segment and appendix in patients with exstrophy-epispadias complex: the first report of a new surgical approach

Objective We aimed to describe our experience in administering an innovative surgical technique to treat pediatric cases of exstrophy-epispadias complex. Material and methods Between 1995 and 2004, seven consecutive patients (six males) with exstrophy-epispadias complex were treated using ileocecal segment for bladder augmentation and appendix for urethral reconstruction. In a single-stage operation, the exstrophied bladder was dissected- and a segment of cecum, ascending colon, terminal ileum, and the corresponding appendix were isolated. Using the opened colon to augment the bladder, the ileal segment was fashioned to skin as temporary stoma, and the appendix was laid in the urethral lumen as the neourethra following urethral demucosation. This technique was used as a secondary surgery in one case and as a primary surgery in six neonates. Evaluation of the urinary tract status was performed by cystograms and ultrasonograms. Results Renal function was saved in all cases and continence was achieved by clean intermittent catheterization every two hours either via the neourethra (n = 6) or through the temporary stoma (n = 1). The patients did not experience any metabolic complications in their follow-ups. Moreover, no one had vesicourethral reflux, dehiscence, or fistula. Conclusions The technique was deemed safe with acceptable outcomes even when secondary repair of previously failed operation was intended. Experiencing the technique in larger cohorts as well as longer follow-ups might be necessary to assess probable long-term complications.     

Follow-up of newborns treated with extracorporeal membrane oxygenation: a nationwide evaluation at 5 years of age

Introduction  

Extracorporeal membrane oxygenation (ECMO) is a supportive cardiopulmonary bypass technique for babies with acute reversible cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of five years, when they start primary school and major decisions for their school careers must be made.     

Longitudinal correlates of the persistence of irregular eating from age 5 to 14 years

Aim:  To report the stability of parent-perceived child irregular eating from 6 months to 14 years of age and to investigate a predictive model inclusive of child and parent factors.
Methods:  Of the 7223 singleton children in a birth cohort, 5122 children were re-interviewed at 5 years and 4554 for the 14-year analysis. Information was obtained from structured interviews including questions answered by parents of the child at birth, 6 months, 5 years and 14 years; and by teenagers at age 14 years and from physical measures of the child. The mother's perception that the child was an irregular eater at age 14 years was the major outcome variable of interest.
Results:  Approximately 40% of irregular eaters at age 5 will still be irregular eaters at age 14 years. This was not related to maternal education or socio-economic class. Significant at multivariate analysis were infant feeding problems and the children's ability to regulate their sleep and mood. Significant maternal factors were greater age, not feeling positive about the baby and persistent maternal anxiety during the child's early years.
Conclusion:  Irregular eating behaviour displays considerable continuity from childhood to mid-adolescence. Independent contributions to this behavioural phenotype include child biological and psychological factors and maternal anxiety during the child's early years.