Samar Marzouk

Correlations of Urinary Biomarkers, TNF-Like Weak Inducer of Apoptosis (TWEAK), Osteoprotegerin (OPG), Monocyte Chemoattractant Protein-1 (MCP-1), and IL-8 with Lupus Nephritis

ObjectiveThis case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.Patients and MethodsIn 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.ResultsSignificantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).ConclusionsUrinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.

Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients

Abstract Background. Left ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and has an important prognostic value in patients with end-stage renal disease (ESRD). Vitamin D receptor (VDR) has been intensively investigated, and one of these (BsmI) already has been associated with survival in the dialysis population. Objective. The aim of this study was to investigate the role of VDR polymorphism (BsmI) on the development of ventricular hypertrophy and atherosclerosis in hemodialysis patients. Subject and methods. The subjects were 80 patients with end-stage renal disease on maintenance hemodialysis, and 40 healthy controls. Clinical and laboratory parameters, including genetic variation in VDR gene (BsmI), were assessed. In addition, echocardiography and intima-media thickness were performed for all subjects. Results. There was no significant difference in the distribution of BsmI genotypes either in patients or in the control group. The frequency of the B allele of BsmI polymorphism (41.6%) in dialysis patients was similar to that of healthy control subjects (39.2%). Patients with BB genotype had significantly lower serum concentrations of 25-hydroxy vitamin D compared to both Bb and bb genotypes. The number of B alleles was positively correlated with left ventricular mass index (LVMI), but not with intima-media thickness. Conclusion. These results suggest that the B alleles of the BsmI polymorphism could be considered as novel markers of altered vitamin D signaling in ESRD patients, and this alteration in BB genotype produces an increase in left ventricle mass.

The Role of PDE5 Inhibitors in Heme Oxygenase–cGMP Relationship in Rat Cavernous Tissues

INTRODUCTION Heme oxygenase (HO) enzyme catalyzes oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO shares many properties with nitric oxide (NO) including the activation of soluble guanyl cyclase. AIM To assess cavernous tissue HO activity and cyclic guanosine monophosphate (cGMP) levels in response to oral phosphodiesterase type 5 (PDE5) inhibitors. METHODS Seven hundred twenty male Sprague-Dawley rats, divided into six groups, were investigated. Group 1, controls; group 2 received sildenafil citrate orally; group 3 received vardenafil hydrochloride; and group 4 received tadalafil. Group 5 was subdivided into three equal subgroups, received the same dose of each drug added to the HO inhibitor, Zn protoporphyrin. Group 6 was subdivided into three equal subgroups, received the same dose of each drug added to the NO inhibitor, L-nitroarginine methylester. Eight rats from each group/subgroup were sacrificed at 0.5, 1, 2, 3, 4, 6, 18, 24, and 36 hours, respectively. MAIN OUTCOME MEASURES HO enzyme activity assay and cGMP tissue levels in dissected rat cavernous tissues. RESULTS Both cavernous tissue HO enzyme activity and cGMP levels were increased significantly in sildenafil-, vardenafil-, and tadalafil-treated rats compared with the controls, with significant decreases after either HO or NO inhibition. Cavernous tissue HO enzyme activity and cGMP showed a positive significant correlation (r = 0.854, P < 0.001). CONCLUSION The effects of PDE5 inhibitors in cavernous tissue are partly mediated through HO enzyme activity.

Oral phosphodiesterase-5 inhibitors: effect of heme oxygenase inhibition on cGMP signalling in rat cavernous tissue.

This work postulated that heme oxygenase (HO) is partly responsible for controlling phosphodiesterase‐5 inhibitor actions by modulating cyclic guanosine monophosphate (cGMP) cavernous tissue levels. Five hundred and four male Sprague–Dawley rats, divided into five groups, were investigated. Group 1 (n = 72) included controls, group 2 (n = 72) received sildenafil citrate (ViagraR) orally, group 3 (n = 72) received vardenafil hydrochloride (LevitraR), group 4 (n = 72) received tadalafil (CialisR). Group 5 (n = 216), subdivided into three subgroups (A, B and C, 72 each), received the same dose of each drug with the HO inhibitor, Zn protoporphyrin. Eight rats from each group/subgroup were killed at 0.5, 1, 2, 3, 4, 6, 18, 24 and 36 h when cGMP levels in the cavernous tissues were estimated. Cavernous tissue cGMP levels increased significantly in sildenafil, vardenafil and tadalafil‐treated rats compared to the controls with significant decreases after HO inhibition. It is concluded that the effects of these PDE‐5 inhibitors in rat cavernous tissue are partly mediated through HO activity via the cGMP signalling pathway.

Elevated serum TRAIL levels in scleroderma patients and its possible association with pulmonary involvement

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to be involved in the pathophysiology of some autoimmune diseases as systemic lupus erythematosus, ankylosing spondylitis, and multiple sclerosis. The aim of this study was to assess serum TRAIL concentration in systemic sclerosis (SSc) patients and to investigate its possible association with various disease parameters. Thirty SSc patients as well as 25 rheumatoid arthritis (RA) patients and 25 healthy volunteers were included in the present study. Organ system involvement in SSc patients was investigated. Pulmonary function tests as well as chest high-resolution computed tomography (HRCT) were done to detect pulmonary involvement in our patients. TRAIL concentrations were measured in the sera of SSc patients, RA patients and healthy controls by enzyme-linked immunosorbent assay. Mean serum TRAIL levels were significantly higher in SSc patients than in the control RA patients and in healthy controls (p < 0.001) while they were not significantly different between patients with diffuse cutaneous SSc and patients with limited cutaneous scleroderma. Serum TRAIL levels were significantly higher in SSc patients with pulmonary involvement and were significantly correlated with HRCT scores. Serum TRAIL levels are significantly elevated in SSc patients and are associated with SSc-associated pulmonary involvement denoting a possible role of TRAIL in the pathogenesis of SSc. Further studies may be needed to confirm these findings and the possible use of TRAIL in detection and possibly treatment of SSc-associated pulmonary disease.

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4.

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon‐based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa‐2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real‐time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide −155, −443 and −1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at −443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide −443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment. Copyright

Bronchial aspirates glucose level as indicator for methicillin-resistant Staphylococcus aureus (MRSA) in intubated mechanically ventilated patients.

This study evaluated if the level of glucose in bronchial aspirate serves as indicator for the risk of MRSA infection in intubated mechanically ventilated ICU patients. A total of 50 critically ill patients was enrolled and were under tight glycemic control to abolish the effect of hyperglycemia on bronchial secretion, if they were expected to require mechanical ventilation for more than 48 hours. Bronchial aspirates were detected for glucose and sent twice weekly for microbiological analysis and whenever an MRSA was expected. The results showed that all the patients had glucose tested in bronchial aspirates. Glucose was detected in bronchial aspirates of 28 of the 50 patients. Glucose in bronchial aspirates in these patients ranged between (2.9-5.1 mmol/l). MRSA was detected in 22 patients where 28 were MRSA free of the MRSA patients 19 had positive glucose where glucose was positive in 28 patients of them 19 (86.4%) where MRSA positive to 9 with no MRSA (32.1%).The risk of having MRSA present markedly increased significantly in the presence of glucose: (p value .001).

Pilot study on molecular quantitation and sequencing of endometrial cytokines gene expression and their effect on the outcome of in vitro fertilization (IVF) cycle

Human trophoblast invasion and differentiation are essential for successful pregnancy outcome. The molecular mechanisms, however, are poorly understood. Interleukin (IL)-11, a cytokine, regulates endometrial epithelial cell adhesion. Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. The present study aimed to assess the levels of LIF, IL-11, and IL-11 α receptor gene expression in the endometrium of women undergoing IVF and correlate their levels with the IVF pregnancy outcome. Also, the study aimed to detect any mutation in these three genes among IVF pregnant and non-pregnant women versus control menstrual blood of fertile women. Endometrial tissue biopsies were taken from 15 women undergoing IVF on the day of oocyte retrieval. The quantitative expression of IL-11, IL-11Rα, and LIF genes was assessed by real-time PCR and PCR products were sequenced. Menstrual blood from 10 fertile women was used as control to compare the DNA sequence versus DNA sequence of the studied genes in endometrial biopsies. LH, FSH, and E2 were assessed for enrolled patients by ELISA. Endometrial thickness was also assessed by pelvic ultrasonography. No significant difference was detected between quantitative expression of the three studied genes and pregnancy IVF outcome. Although DNA sequence changes were found in IL-11 and LIF genes of women with negative pregnancy IVF outcome compared to women with positive pregnancy IVF outcome, no DNA sequence changes were detected for IL-11Rα. Other studied parameters (e.g., age, LH, FSH, E2, and endometrial thickness) showed no significant differences or correlation of quantitative expression of the three studied involved genes. Data suggested that there were no significant differences between quantitative expression of IL-11, IL-11Rα, and LIF genes and the IVF pregnancy outcome. The present study may reveal that changes in IL-11 and LIF genes sequence may contribute in pregnancy IVF outcome.

Comparative diagnostic study of biomarkers using FibroMax™ and pathology for prediction of liver steatosis in patients with chronic hepatitis C virus infection: an Egyptian study

Background: Steatosis is common in patients with hepatitis C virus (HCV) infection and may be a major determinant of progression of liver injury. This study evaluated FibroMax™ for noninvasive diagnosis of steatosis in patients with chronic HCV. Methods: This cross-sectional study included 44 patients naïve to treatment who were referred to our hepatology clinic for assessment of fitness for antiviral therapy. Chronic HCV infection was diagnosed by viral markers. Investigations included assessment of abdominal ultrasonography, liver biopsy, calculation of body mass index, and biomarker parameters in serum using FibroMax. Results: Histopathology of liver biopsies showed steatosis in 30 of 44 (68%) patients. FibroMax results were positively correlated with viral load by quantitative polymerase chain reaction and histopathological findings. Body mass index was significantly higher in steatotic patients (P = 0.003) and was significantly associated with the results on FibroMax (P = 0.005). Conclusion: FibroMax was correlated with histopathology and body mass index in patients with HCV. Abdominal ultrasonography could not be used as a single tool to diagnose steatosis with HCV. Steatosis is correlated with viral load, which suggests a direct viral effect. We recommend FibroMax assessment in a larger number of patients to assess its applicability in patients with HCV and steatosis.

Neupogen and mesenchymal stem cells are the novel therapeutic agents in regeneration of induced endometrial fibrosis in experimental rats

Endometrial fibrosis is the presence of intrauterine adhesions (IUAs) after any uterine surgery or curettage and it results in infertility and recurrent pregnancy loss. We evaluated the role of human mesenchymal stem cells (hMSCs) as a therapeutic agent of endometrial fibrosis. We also compared the effect of MSCs with the effect of estrogen and neupogen either each alone or as a combined therapy with MSCs. This experimental study was performed on 84 albino rats which were divided into seven groups (n=12 rats/group) as follows, group1: normal control rats, group 2: induced fibrosis, group 3: induced fibrosis that received oral estrogen, group 4: induced fibrosis that received hMSCs, group 5: induced fibrosis that received hMSCs and estrogen, group 6: induced fibrosis that received neupogen, and group 7: induced fibrosis that received hMSCs and neupogen. The extent of fibrosis, vascularization, and inflammation were evaluated by; qRT-PCR for interleukin 1 (IL-1), interleukin 6 (IL-6), TNF, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and RUNX; ELISA for connective tissue growth factor (CTGF); Western blotting for collagen-I; immunohistochemistry examination for VEGF and RUNX-2; and histopathological assessment. In therapeutic groups either by hMSCs alone or combined with estrogen or neupogen; fibrosis and inflammation (IL-1, IL-6, TNF, TGF-β, RUNX, CTGF, and collagen-I) were significantly decreased but vascularization (VEGF) was significantly increased (P<0.05) compared with induced fibrosis group. The most significant result was obtained in fibrosis that received combined therapy of hMSCs and neupogen (P=0.000). Stem cells and neupogen are a highly effective alternative regenerative agents in endometrial fibrosis.