Serum mucosa-associated epithelial chemokine (MEC/CCL28) in atopic dermatitis: a specific marker for severity

Background: Mucosa-associated epithelial chemokine (MEC; CCL28) is considered pivotal in mediating migration of CCR3 and CCR10-expressing skin-homing memory CLA+ T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases such as atopic dermatitis (AD). Objective: This controlled longitudinal study was designed to evaluate the expression of CCL28 serum levels in childhood AD and bronchial asthma (BA), and its possible relations to disease severity and activity. Methods: Serum CCL28 levels were measured in 36 children with AD, 23 with BA, and 14 who had both conditions as well as in 21 healthy age and sex-matched subjects serving as controls. Sixteen patients in the AD group were followed up and re-sampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables. Results: Serum CCL28 levels in AD whether during flare (median = 1530; mean ± SD = 1590.4 ± 724.3 pg/ml) or quiescence (median = 1477, mean ± SD = 1575.2 ± 522.1 pg/ml) were significantly higher than the healthy children values (median = 301; mean ± SD = 189.6 ± 92.8 pg/ml). However, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median = 340; mean ± SD = 201.6 ± 109.5 pg/ml) were significantly lower than the AD group and comparable to the healthy control values. Serum CCL28 levels in severe AD were significantly higher as compared to mild and moderate cases and correlated positively to the calculated severity scores (LSS and SCORAD). CCL28 levels during exacerbation of AD could be positively correlated to the corresponding values during remission, the peripheral absolute eosinophil counts and serum lactate dehydrogenase levels. Serum CCL28 did not vary with the serum total IgE values in AD. Conclusion: Our data reinforce the concept that CCL28 might share in the pathogenesis of AD probably through selective migration and infiltration of effector/memory Th2 cells into the skin. It may also represent an objective prognostic marker for disease severity. Further studies may pave way for CCL28 antagonism among the adjuvant therapeutic strategies.Keywords: Mucosa-associated epithelial chemokine, CCL28, allergic diseases, atopic dermatitis, bronchial asthmaEgypt J Pediatr Allergy Immunol 2005; 3(2): 64-7

Plasma macrophage-derived chemokine (CCL22) and its receptor CCR4 on peripheral blood T lymphocytes of asthmatic children

Background: The macrophage-derived chemokine (MDC/CCL22) acts on CC chemokine receptor-4 (CCR4) to direct trafficking and recruitment of T helper-2 (TH2) cells into sites of allergic inflammation. It was previously found overexpressed in lesional samples from adult asthmatics. Objective: This study is aimed to investigate the participation of CCR4/MDC axis in the development of TH2-dominated allergen-induced childhood asthma in relation to disease activity, attack severity, and response to therapy, and to outline its value in differentiating atopic asthma from infection-associated airway reactivity. Methods: Proportion of CCR4-expressing peripheral blood T lymphocytes (CCR4+PBTL%) were purified and quantitated by negative selection from peripheral blood mononuclear cells by flow cytometry, and the concentration of MDC in plasma was measured by ELISA in 32 children with atopic asthma (during exacerbation and remission), as well as in 12 children with acute lower respiratory tract infections (ALRTI), and 20 healthy children serving as controls. Results: The mean plasma MDC level (925±471.5 pg/ml) and CCR4+PBTL% (55.3±23.6%) were significantly higher in asthmatic children during acute attacks in comparison to children with ALRTI (109±27.3 pg/ml and 27.6±7.5%) and healthy controls (99.6±25.6 pg/ml and 24.2±4.1%). Both values decreased significantly after subsidence of attacks (502±284.3 pg/ml and 32.5±10.5%) although remained higher than the other 2 groups which were actually comparable in terms of MDC and CCR4%. MDC and CCR4% values were higher among children with acute severe than mild or moderate asthma exacerbations, and in persistent than intermittent cases during stability. Positive correlations could be elicited between both markers during exacerbation or stability, and between the exacerbation level of each and its corresponding value during remission. Corticosteroid-treated patients had the highest expression of both markers when relation to therapy was studied. Conclusion: Our findings reinforce the concept that up regulation of CCR4/MDC axis is implicated in the pathogenesis of pediatric atopic asthma and may represent a useful biomarker of monitoring allergic inflammation and response to therapy. Neutralization and manipulation of CCR4-expressing T cells, as well as MDC antagonism, may represent an adjuvant in the treatment of severe allergic disorders.Keywords: MDC; CCR4; T-lymphocytes; flowcytometry; asthma; childrenEgypt J Pediatr Allergy Immunol 2005; 3(1): 20-3

Cholestasis in patients with Cockayne syndrome and suggested modified criteria for clinical diagnosis

<p>Abstract</p> <p>Background</p> <p>Cockayne syndrome is a rare autosomal recessive neurodegenerative disease characterized by low-to-normal birth weight; growth failure; brain dysmyelination with calcium deposits, cutaneous photosensitivity; pigmentary retinopathy, cataract, and sensorineural hearing loss. To the best of our knowledge, cholestatic liver disease was not previously reported in these patients.</p> <p>Aim</p> <p>To highlight the presence of cholestasis and liver dysfunction in this group of patients and to suggest modified criteria for clinical diagnosis.</p> <p>Methods</p> <p>The study included nine patients with Cockayne from four different families (five males and four females) in which Cockayne was suspected clinically. In all patients chromosomal breakage studies revealed mild (45%) to moderate (60%) increase in frequency of chromatid and chromosome gaps and breaks versus 25% in normal controls. Diagnosis was confirmed by DNA repair assay.</p> <p>Results</p> <p>During routine follow up of these patients, seven of them had evident liver affection ranging from mild elevation in liver enzymes to cholestatic liver disease and liver cell failure. The attacks were recurrent in two patients and were sometimes preceded by infection. The attack may lead to deterioration of neurological and/or liver condition. It may end in liver cell failure that either recovers completely or may lead to death.</p> <p>Conclusions</p> <p>liver disease could be considered common in Egyptian patients with Cockayne with the cholestatic form being the most evident. The syndrome should be included in the list of causes of cholestatic liver disease. Chromosomal breakage study and positive family history should be included as major criteria for clinical diagnosis of Cockayne especially in a population like ours where consanguineous marriage is very high and molecular testing and UV sensitivity tests are considered unaffordable.</p

Serum OX40 ligand: a potential marker of atopic dermatitis disease severity in children

Background: OX40 ligand (OX40L) and OX40 are members of the tumor necrosis factor (TNF) and TNF receptor (TNFR) super families respectively. Recent studies have indicated the critical involvement of OX40/OX40L interaction in the pathogenesis of atopic dermatitis. To our knowledge, no data could be cited in literature concerning OX40L levels in serum or in other biological fluids of atopic dermatitis children. Objective: This study was done to explore the expression of OX40L in the serum of atopic dermatitis children with respect to disease activity and severity. Methods: This follow-up, case-control longitudinal study was conducted on 64 children as a stratified non-random sample; 34 with atopic dermatitis and 30 healthy children. Serum concentrations of OX40L were measured by sandwich enzyme immunoassay. The severity of atopic dermatitis was assessed according to the Leicester Sign Score (LSS), Simple Scoring System (SSS), Scoring Atopic Dermatitis (SCORAD) index, and Objective SCORAD. Results: Serum OX40L levels (pg/ml) in atopic dermatitis patients were significantly elevated as compared to controls (176.6 ± 45.9) whether during flare (1007 ± 241.5) or quiescence (699 ± 198.5). There were significant positive correlations between serum OX40L levels and each of the LSS, SSS and SCORAD indices of atopic dermatitis disease severity, while it was insignificant regarding the objective SCORAD. However, when atopic dermatitis children were classified according to the objective SCORAD index of severity into mild, moderate and severe, it was found that the mean serum level in the severe group was significantly higher than the corresponding values of the mild or the moderate group. OX40L levels did not correlate with serum total IgE or absolute eosinophils count. Serum total LDH levels correlated positively with each of the serum OX40L levels and the LSS and SCORAD indices of severity. Conclusions: Serum OX40L level is an objective reliable marker of atopic dermatitis severity in children. It may be useful for follow up and may help to improve research and management of this disease. Blockade of interactions between OX40 on Th2 cells and OX40L on activated dendritic cells using an OX40L-specific monoclonal antibody could represent a novel strategy for the treatment of atopic dermatitis.Keywords: Atopic dermatitis, LSS, OX40, OX40L, SCORAD, SSS, TNFEgypt J Pediatr Allergy Immunol 2009;7(1):15-2

Gender differences in fasting serum leptin level among Malaysian population

Serum leptin increases with progressive obesity in both genders. However, for any given measure of obesity, leptin levels are higher in women than men. This research is to study the gender differences of the fasting plasma leptin concentration in Malaysian people from east coast Malaysia with a back ground knowledge of ethnic variation. To be as a baseline for future research, and to consolidate our knowledge regarding leptin and it’s correlation with endocrine disorders. Objective: To study the gender differences of the plasma leptin and its relationship to the ethnic group, so that can establish a base line for future studies regarding leptin hormone and it’s association with different endocrine and fertility issues Method: This was a cross sectional study included 100 consented Malaysian people(50 male and female) were recruited from Kulliyyah of dentistry, International Islamic University Malaysia and medical department, Hospital Tengku Ampuan Afzan, Kuantan, those with endocrine, diabetic illness, abnormal BMI, chronic illness and any patient on hormonal treatment were excluded from the study. Individual venous blood was taken between 0800–0900 am after an overnight fasting. Determination of serum leptin was done by enzyme linked immune-sorbent assay (ELISA)and measured in ng/ml. Data were analyzed using SPSS 18 Result:. Mean age were, 34.5±6.4 and 31.2± 4.3 for male and female respectively, there was no significant difference between the age of both groups. Mean body mass index for male was 23 ± 1.91 Kg / m2 which were not significantly different from the female BMI which was 22 ± 0.87 Kg / m2. data were analysed by Mann-Whitney U-test, found that serum leptin levels in females are significantly higher (Z= 6.0, p<0.001) than those in males, 7.29 ng/ml vs 3.94 ng/ml respectively. Correlation coefficient of serum leptin level with female body mass index (kg/m2) is 0.693 in a value of <.0001 conclusion: Serum leptin is significantly affected by gender, with women have significantly higher serum leptin level than man, further study is required to measure the fat mass in addition to serum leptin in both genders as a possible reason for this difference,. Keywords LEPTIN , GENDER, Ethnic variatio

The FGFR4-G388R Polymorphism Promotes Mitochondrial STAT3 Serine Phosphorylation to Facilitate Pituitary Growth Hormone Cell Tumorigenesis

Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders

Factor V G1691A (Leiden) is a major etiological factor in Egyptian Budd-Chiari syndrome patients

Objective: Budd-Chiari syndrome is a multifactorial disease in which several prothrombotic disorders may predispose patients to the development of thrombosis at this uncommon location (hepatic veins). The aim of this study was to determine the prevalence and characteristics of inherited thrombophilia in Egyptian Budd-Chiari syndrome patients.Materials and Methods: The study included 47 Budd-Chiari syndrome patients (20 children and 27 adults). Genotyping of Factor V G1691A (Leiden), prothrombin G20210A (PT), and methylenetetrahydrofolate reductase C677T were performed using real-time PCR and fluorescence melting curve detection analysis.Results: Factor V Leiden was observed in 29 patients (61.7%). It is the only factor that caused Budd-Chiari syndrome in 18 of the patients and in 5 of the patients with inferior vena cava involvement. Myeloproliferative disease was noted in 12 (25.5%) patients, antiphospholipid syndrome in 5 (10.6%), and Behcet’s disease in 3 (6.4%). Interestingly, 3 of the children with Budd-Chiari syndrome had lipid storage disease.Conclusion: Factor V Leiden was a major etiological factor in Egyptian Budd-Chiari syndrome patients, which may have been related to the high frequency of this mutation in the study region. Factor V Leiden was also a strong thrombophilic factor and the leading cause of inferior vena cava thrombosis in these patients. Lipid storage disease should be included as a risk factor for Budd-Chiari syndrome

Prosopis juliflora leave extracts induce cell death of MCF-7, HepG2, and LS-174T cancer cell lines

Prosopis juliflora (P. juliflora) is a widespread phreatophytic tree, which belongs to the Fabaceae family. The goal of the present study is to investigate the potential anti-cancer effect of P. juliflora leave extracts and to identify its chemical composition. For this purpose, MCF-7 (breast), HepG2 (liver), and LS-174T (colorectal) cancer cell lines were cultivated and incubated with various concentrations of P. juliflora leave extracts, and its impact on cell viability, proliferation, and cell cycle stages was investigated. P. juliflora leave extracts induced concentration-dependent cytotoxicity against all tested cancer cell lines. The calculated IC50 was 18.17, 33.1 and 41.9 μg/ml for MCF-7, HePG2 and LS-174T, respectively. Detailed analysis revealed that the cytotoxic action of P. juliflora extracts was mainly via necrosis but not apoptosis. Moreover, DNA content flow cytometry analysis showed cell-specific anti-proliferative action and cell cycle stages arrest. In order to identify the anti-cancer constituents of P. juliflora, the ethyl extracts were analyzed by liquid chromatography-mass spectrometry. The major constituents identified in the ethyl extracts of P. juliflora leaves were hydroxymethyl-pyridine, nicotinamide, adenine, and poly-(methyl methacrylate) (PMMA). In conclusion, P. juliflora ethyl acetate extracts have a potential anti-cancer effect against breast adenocarcinoma, hepatocellular carcinoma, and colorectal adenocarcinoma, and is enriched with anti-cancer constituents

Neuroprotective and anti-inflammatory effects of Rhus coriaria extract in a mouse model of ischemic optic neuropathy

Modulating oxidative stresses and inflammation can potentially prevent or alleviate the pathological conditions of diseases associated with the nervous system, including ischemic optic neuropathy. In this study we evaluated the anti-neuroinflammatory and neuroprotective activities of Rhus coriaria (R. coriaria) extract in vivo. The half maximal inhibitory concentration (IC50) for DPPH, ABTS and \u3b2-carotene were 6.79 \ub1 0.009 \u3bcg/mL, 10.94 \ub1 0.09 \u3bcg/mL, and 6.25 \ub1 0.06 \u3bcg/mL, respectively. Retinal ischemia was induced by optic nerve crush injury in albino Balb/c mice. The anti-inflammatory activity of ethanolic extract of R. coriaria (ERC) and linoleic acid (LA) on ocular ischemia was monitored using Fluorescence Molecular Tomography (FMT). Following optic nerve crush injury, the mice treated with 400 mg/kg of ERC and LA exhibited an 84.87% and 86.71% reduction of fluorescent signal (cathepsin activity) respectively. The results of this study provide strong scientific evidence for the neuroprotective activity of the ERC, identifying LA as one of the main components responsible for the effect. ERC may be useful and worthy of further development for its adjunctive utilization in the treatment of optic neuropathy

On the stability in phase-lag heat conduction with two temperatures

We investigate the well-posedness and the stability of the solutions for several Taylor approximations of the phase-lag two-temperature equations.We give conditions on the parameters which guarantee the existence and uniqueness of solutions as well as the stability and the instability of the solutions for each approximationPeer ReviewedPostprint (author's final draft