Natural killer cells, glutathione, cytokines, and innate immunity against Mycobacterium tuberculosis.

It is becoming increasingly apparent that natural killer (NK) cells play a crucial role in innate defense mechanisms against Mycobacterium tuberculosis infection. Furthermore, NK cell functions are dependent on adequate levels of glutathione. In this study, we examined whether the NK cell-mediated growth control of intracellular M. tuberculosis is dependent on adequate levels of glutathione. We investigated the effects of glutathione both alone and in combination with interleukin-2 (IL-2) or IL-12 or both in modulating NK cell functions, such as cytolytic activity, activating receptor expression, induction of apoptosis, and cytokine synthesis. Our results strongly indicate that glutathione in combination with IL-2+IL-12 augments NK cell functions, leading to control M. tuberculosis infection.     

Circulating tumor and cancer stem cells in hepatitis C virus-associated liver disease

AIM: To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C virus (HCV)-associated liver disease.METHODS: Blood and/or tissue samples were obtained from HCV (genotype 4)-associated hepatocellular carcinoma patients (HCC; n = 120), chronic hepatitis C patients (CH; n = 30) and 33 normal control subjects (n = 33). Serum levels of alpha-fetoprotein (AFP), alkaline phosphatase, and alanine and aspartate aminotransferases were measured. Cytokeratin 19 (CK19) monoclonal antibody was used to enumerate CTCs, and CD133 and CD90 were used to enumerate CSCs by flow cytometry. The expression levels of the CSCs markers (CD133 and CD90) as well as telomerase, melanoma antigen encoding gene 1 (MAGE1) and MAGE3 were assessed by RT-PCR and quantitative real-time polymerase chain reactions. The number of CTCs and/or the expression levels of CK19, CD133, telomerase, MAGE1 and MAGE3 were correlated to the standard clinicopathologic prognostic factors and disease progression.RESULTS: Levels of AFP, alkaline phosphatase and aspartate aminotransferase were significantly different among the HCC, CH and control groups (P < 0.001), whereas alanine aminotransferase differed significantly between patient (HCC and CH) and control groups (P < 0.001). At the specified cutoff values determine by flow cytometry, CK19 (49.8), CD90 (400) and CD133 (73) were significantly higher in the blood of HCC patients compared to those in the CH and control groups (P < 0.001). On the other hand, CD133 at a 69.5 cutoff was significantly higher in the CH compared to the control group (P ≤ 0.001). Telomerase, MAGE1 and MAGE3 RNA were expressed in 55.71%, 60.00% and 62.86% of the HCC patients, respectively, but were not detected in patients in the CH or control groups, which were statistically significant (Ps < 0.001). The expression levels of telomerase, CD90, MAGE3, CD133 and CK19 were all significantly associated with high tumor grade and advanced stage in HCC patients (all Ps < 0.05).CONCLUSION: CTC counts and AFP, CK19, telomerase, and MAGE1/MAGE3 expression predict disease progression in patients with HCV, whereas telomerase, MAGE3, CD90, CD133 and CK19 are prognostic markers in HCC.     

Liver fatty acid binding protein: A potential urinary and tissue biomarker for lupus nephritis

Aim of the work

To assess urinary liver fatty acid binding protein (uL-FABP) levels and tissue expression (tL-FABP) in renal biopsies of active and inactive lupus nephritis (LN) patients and examine their relationship with disease characteristics.

Evaluation of IL-34 in psoriasis and psoriatic arthritis patients: Correlation with disease activity and severity

Introduction

Interleukin-34 (IL-34) is a newly discovered cytokine essential for skin homoeostasis. It is involved in macrophage differentiation, osteoclastogenesis and inflammation. This could suggest a potential role in the pathogenesis of psoriasis and psoriatic arthritis (PsA).

Unilateral Versus Bilateral Laparoscopic Ovarian Drilling Using Thermal Dose Adjusted According to Ovarian Volume in CC-Resistant PCOS,A Randomized Study

Objective

This study aimed to evaluate the efficacy of unilateral laparoscopic ovarian drilling versus bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume in clomiphene citrate (CC)-resistant PCOS patients in terms of endocrine changes, menstrual cycle resumption, ovulation and pregnancy rates.

Patients and Methods

This study was conducted in the Department of Obstetrics and Gynecology, Zagazig university hospitals. One hundred CC-resistant PCOS patients were divided into two groups. Group (I) (50 patients) underwent unilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume (60 J/cm³ of ovarian tissue), and group (II) (50 patients) underwent bilateral laparoscopic ovarian drilling using the same previously mentioned thermal dose. Endocrinal changes and menstrual cycle resumption were assessed within 8 weeks postoperatively, but the ovulation and pregnancy rates were estimated after 6-month follow-up period.

Results

There was no statistically significant difference between the two groups as regards demographic data (p > 0.05). As regards menstruation cycle resumption (62.5 vs. 81%) (p = 0.047), total ovulation rate (54.2 vs. 78.7%) (p = 0.011) and cumulative pregnancy rate (33.3 vs. 55.3%) (p = 0.031), there was statistically significant difference between both groups. After drilling, there were highly statistically significant decrease in the mean serum levels of luteinizing hormone (LH) and significant decrease in the mean serum levels of testosterone in both groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in both groups after drilling.

Conclusion

Bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume is more effective than the right-sided unilateral technique with thermal dose adjusted according to ovarian volume in terms of menstrual cycle resumption, ovulation and cumulative pregnancy rates in CC-resistant PCOS patients.

     

Prevalence of antinuclear antibodies in healthy Lebanese subjects, 2008–2015: a cross-sectional study involving 10,814 subjects

Antinuclear antibodies (ANA) are found at varying frequencies in healthy populations, depending on geographical location and ethnic background of participants. The main objective of this study was to determine the prevalence of ANA in healthy Lebanese population in the period 2008–2015. Study subjects comprised 10,851 individuals (3311 males and 7503 females). ANA positivity was determined using immunofluorescence on HEp-2 cells. The prevalence of positive ANA test at a titer of ≥1:100 was 26.4 %, with 696 individuals (6.4 %) having titers exceeding 1:100. Most ANA-positive cases were recorded between 2013 and 2015, which reflected increased assay sensitivity. ANA positivity was associated with increased age and with female gender. Significant increases in ANA positivity were seen with advanced age, with steady increases from the 30- to 40-year age group through the >70-year age group, with significantly higher prevalence noted in female participants. There was a steady and significant reduction in the number of ANA-positive cases with higher ANA titers, which ranged from 20.0 % (1/100) to 3.7 % (1/320), 1.7 % (1/640), and 1.1 % (1/1000). While 45 % of low ANA titer was seen in 31–60-year age category, compared with 19.8 % for 61+ year category, the distribution of high ANA titer was more uniform between 31+ year age categories, which ranged from 11.4 % (31–40 years) to 12.4 % (>70 years). This was consistently and significantly higher in female participants. The prevalence and distribution of ANA among Lebanese individuals were comparable to the rates established for Western countries and confirm the contribution of female gender and advanced age to ANA positivity.     

Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P 0.01,P 0.001 and P 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.     

Perceived Risk of Cervical Cancer and Barriers to Screening among Secondary School Female Teachers in Al Hassa,Saudi Arabia

Background: No previous studies had addressed the perceived risk of cervical cancer (CC) and its influence on screening practices and perceived barriers in Saudi Arabia. Methods: This cross-sectional study was conducted on 506 randomly selected Saudi female secondary school teachers in Al Hassa, Saudi Arabia to assess their level of knowledge about risk factors and signs of CC in relation to perceived risk and to characterize CC screening compliance using a self-administered questionnaire. Results: Of the included female Saudi teachers, 65.4% and 63.4% were considered less-knowledgeable about CC risk factors and early signs and symptoms respectively. Only 17.2% reported being previously examined for CC. The majority of participants perceived themselves to be at an average or below average risk of CC. Residing in urban areas was the strongest predictor of CC screening (Odds ratio ‘OR’= 3.39; 95% confidence intervals ‘CI= 1.76-6.46; P=0.001). Awareness of risk factors was significantly associated with higher awareness of signs of CC (OR 2.5; 95% CI=, P=0.001). Exploratory factor analysis showed that personal fears (of screening being embarrassing) was the major factor that hindered CC screening with a high loading eigenvalue of 4.392, explaining 30.8% of the barriers toward utilization, followed by health care related factors. Conclusion: Secondary school teachers in Al Hassa, Saudi Arabia showed low perceived risk, poor awareness about risk factors, signs and symptoms of CC and limited uptake of screening practices. This underlines the need for education programs on CC targeting this group.     

Identification of insulin gene variants in neonatal diabetes

Objectives: Permanent neonatal diabetes (PNDM) is caused by mutations in the genes responsible for the synthesis of different proteins that are important for the normal behavior of beta cells in the pancreas. Mutations in the insulin gene (INS) are considered as one of the causes of diabetes in neonates. This study aimed to investigate the genetic variations in the INS gene in a group of Egyptian infants diagnosed with PNDM.

Methods: We screened exons 2 and 3 with intronic boundaries of the INS gene by direct gene sequencing in 30 PNDM patients and 20 healthy controls. A detailed clinical phenotyping of the patients was carried out to specify the diabetes features in those found to carry an INS variant.

Results: We identified five variants (four SNPs and one synonymous variant), c(0).187?+?11T?>?C, c.-17-6T?>?A, c.*22A?>?C, c.*9C?>?T, and c.36G?>?A (p.A12A), with allelic frequencies of 96.7%, 80%, 75%, 5%, and 1.7%, respectively. All showed no statistically significance difference compared with the controls, with the exception of c.*22A?>?C.

Conclusion: Genetic screening for the INS gene did not reveal an evident role in the diagnosis of PNDM.