Ayman Z. Elsamanoudy

Seminal clusterin gene expression associated with seminal variables in fertile and infertile men.

PURPOSE CLU is a disulfide linked, heterodimeric protein associated with the clearance of cellular debris and apoptosis. We assessed the association of seminal CLU gene expression with seminal variables in fertile and infertile men. MATERIALS AND METHODS A total of 124 men were divided into healthy, fertile men with normozoospermia, and men with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia. History was obtained, and clinical examination and semen analysis were done. In semen we assessed sperm acrosin activity, sperm DNA fragmentation and seminal CLU gene expression. RESULTS CLU RNA and CLU protein gene expression were significantly increased in semen samples of infertile men with oligoasthenoteratozoospermia > asthenoteratozoospermia > asthenozoospermia compared with healthy, fertile controls. CLU gene expression significantly correlated negatively with sperm count, motility, acrosin activity index, linearity index and linear velocity, and significantly correlated positively with the percent of sperm abnormal forms and DNA fragmentation. CONCLUSION CLU gene expression was significantly increased in the semen samples of infertile men. It correlated negatively with sperm count, motility, acrosin activity, linearity index and linear velocity, and positively with the percent of sperm abnormal forms and DNA fragmentation.

Matrix metalloproteinase-9 expression in lung cancer patients and its relation to serum mmp-9 activity, pathologic type, and prognosis.

Background:Matrix metalloproteinase-9 is closely associated with the invasive and metastatic potential of most types of solid cancers. Our objective was to investigate the MMP-9 expression in lung cancer and to evaluate their relations to histopathologic types and prognosis. Methods:Bronchoscopic samples were obtained from tumor and normal bronchial mucosa in 25 patients with lung cancer. Total RNA was isolated from the tissues, and the relative expression as well as the activity of MMP-9 was evaluated. Results:Non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) showed significantly higher MMP-9 expression (P<0.0001) compared with normal tissues. MMP-9 activity in tissue and serum samples from both cancer groups were significantly higher than normal tissue and serum controls (P<0.0001). Also, MMP-9 expression and tissue and serum activity were significantly higher in NSCLC than in SCLC (P=0.0167, 0.0454, and 0.004, respectively). As regards the pathologic types of NSCLC, similar results were found for the adenocarcinoma subgroup versus squamous cell lung cancer (P=0.0015, 0.0052, and 0.0011, respectively). MMP-9 expression and tissue activity were higher in stage III-IV NSCLC cases compared with early tumor stages (P=0.0120 and 0.0271, respectively). Conclusions:The expression and activity of MMP-9 are upregulated in NSCLC and are related to the pathologic type and clinical stage of NSCLC. Significantly higher expression and activity of MMP-9 in tumor tissue than in the surrounding tissue supports the important role of this metalloproteinase in the growth of lung cancer, and it could be used as a suggested therapeutic target.

Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma.

OBJECTIVE To assess the efficacy of a combination of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa) as natural leukotriene inhibitor, antiinflammatory and antioxidant products respectively in controlling bronchial asthma. SUBJECTS AND METHODS The study comprised 63 patients with bronchial asthma that are further subdivided into two groups .Group 1 receiving oral capsule (combined herb) in a soft-gelatin capsule 3 times daily for 4weeks and group 2 receiving placebo. Plasma leukotriene C(4) (LTC(4))(,) nitric oxide (NO) and malondialdehyde (MDA) levels were measured and pulmonary function was also assessed in all patients enrolled in the study. RESULTS There was a statistically significant decrease in the plasma levels of LTC(4), (MDA), and NO in target therapy group when compared with placebo group. CONCLUSION The used extract contained Boswellia serrata, Curcuma longa and Glycyrrhiza has a pronounced effect in the management of bronchial asthma.

Modulation of metabolic and cardiac dysfunctions by insulin sensitizers and angiotensin receptor blocker in rat model of type 2 diabetes mellitus.

The objective of this study was to investigate the modulation of metabolic dysfunctions, adiponectin levels, and cardiac dysfunctions of type 2 diabetes mellitus (T2DM) by a combination of the insulin sensitizer rosiglitazone and angiotensin receptor blocker telmisartan in an experimental rat model. Fifty male adult Sprague-Dawley rats were divided equally into 5 groups. Group I: fed normal chow; served as normal control group. Groups II-V: fed a high-fat diet (HFD) for 2 weeks, followed by injection of streptozotocin (STZ; 35 mg/kg) to create a model of T2DM. Group II: treated with vehicle. Group III: treated with rosiglitazone (4 mg/kg). Group IV: treated with telmisartan (5 mg/kg). Group V: treated with both agents. Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001). Rosiglitazone exerted more improvement in all parameters than telmisartan did, and a combination of both did not augment the improvement further, except for TGs and adiponectin. For the isolated atrial study, a combination of rosiglitazone and telmisartan corrected the responses of the atria of HFD-STZ rats to the negative inotropic effect induced by adenosine better than either one did alone, whereas this combination, surprisingly, significantly attenuated the positive inotropic response to β-adrenoreceptor and α-adrenoreceptor agonists. In conclusion, rosiglitazone significantly improved the metabolic and cardiac dysfunctions in T2DM. Moreover, a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin, and restored the atrial inotropic response to adenosine. Surprisingly, this combination significantly attenuates the positive inotropic response to α1-adrenoreceptor and β-adrenoreceptor agonists.

Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity.

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and -dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post- but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, -dP/dtmax, and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dtmax. Therefore, we conclude that concurrent or post- but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.

Fibrogenic gene expression in the skin and lungs of animal model of systemic sclerosis: a histological, immunohistochemical and molecular study

Background Systemic sclerosis (SSc) is an autoimmune disorder of unknown origin, characterized by excess accumulation of the extracellular matrix in the skin and other internal organs. Aim of the work The current study was designed to establish an animal model of SSc in order to analyze the histological and immunohistochemical changes in the skin and lungs as well as to try to find a possible pathophysiologic mechanism for this disease by studying the gene expression of some fibrogenic genes. Materials and methods Twenty adult male albino rats were included in this study. They were divided into two groups: the control group (10) and the bleomycin-treated group (10). Histological examination including H&E staining and Masson’s trichrome staining for skin and lung tissue samples and immunohistochemical examination for measuring &agr;-SMA were performed. RNA was extracted from these tissue samples and semiquantitative Rt-PCR for &agr;-SMA, transforming growth factor &bgr; (TGF-&bgr;), and TNF-&agr; was performed. Results Histological changes were observed in SSc, including collagen deposition and increased expression of &agr;-SMA in both skin and lung tissues, with increased dermal thickness in the skin. Moreover, overexpression of &agr;-SMA, TGF-&bgr;, and TNF-&agr; in skin and lung tissues of the SSc group was observed. Conclusion Male rat model is a good model for SSc. &agr;-SMA, TGF-&bgr;, and TNF-&agr; could play a role in the pathophysiologic mechanism of SSc, as they showed overexpression in both skin and lung tissues that correlate with the histological and immunohistochemical findings of the disease.

The Association of XRCC1 Gene Polymorphisms and Chronic Hepatitis C Induced Insulin Resistance in Egyptian Patients

Chronic hepatitis C is implicated in insulin resistance (IR) susceptibility. An X-ray repair cross-complementing group 1 gene (XRCC1) is proposed to be a candidate gene for a study of IR susceptibility. So, this study aims to investigate the possible association of the XRCC1 gene polymorphisms with the risk of IR related to chronic hepatitis C virus (HCV) infection in Egyptian patients. In a case-control study, a total of 210 subjects, including 140 chronic HCV patients (87 patients with IR and 53 without IR) and 70 healthy controls, were included. Two genetic polymorphisms (c.1254C > T and c.1517G > C) of the XRCC1 gene were genotyped via the PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The result of the current study revealed that these two single nucleotide polymorphisms (SNPs) have statistically significant influences on susceptibility to IR in chronic HCV infected Egyptian patients. It could be concluded that c.1254C > T, the TT genotype, CT/CC carriers as well as c.1517G > C, the CC genotype and GC/GG carriers might be associated with increased IR susceptibility. Moreover, T-allele of c.1254C > T and the C-allele of c.1517G > C genetic variants might influence the susceptibility.

Association between E-selectin S128R (A561C) polymorphism and diabetic retinopathy ( a possible relationship)

Background E-selectin is a cell surface glycoprotein that mediates the adhesion of leukocytes to the vessel endothelium. Diabetic retinopathy, a leading cause of vision loss, is associated with altered endothelial function. Endothelial dysfunction, such as that in diabetes, is associated with altered production of leukocyte-adhesive molecules, for example, E-selectin. However, it is unknown whether genetic polymorphism in the E-selectin gene plays a role in diabetic retinopathy. This is a case–control study to determine the frequencies of E-selectin genotypes and allelic forms in diabetic patients having diabetic retinopathy and to evaluate the role of E-selectin gene polymorphism as a predisposing factor for diabetic retinopathy. E-selectin polymorphism was determined in 84 type 2 diabetic patients and in 40 age-matched and sex-matched controls. In the diabetic group, 46 patients had no retinopathy, whereas the other 38 were duration-matched diabetic patients with diabetic retinopathy. E-selectin genotyping was accomplished by PCR amplification, followed by restriction enzyme digestion (restriction fragment length polymorphism). The E-selectin level in plasma was estimated using the enzyme-linked immunosorbent assay (ELISA). In addition, the lipid profile was determined using the colorimetric method. Results In the present case–control study, a total of 85% of controls had the AA genotype, whereas 15% had the AC genotype; the CC genotype was not detected. Frequencies of the AA, CC, and AC genotypes were found to be 37, 32.6, and 30.4% in diabetic patients with no retinopathy and 31.6, 36.8, and 31.6% in diabetic patients with retinopathy respectively. The CC genotype was significantly associated with diabetic patients as a whole (odds ratio: 6.9, 95% confidence interval: 2.2–21.6; P =0.0001), but no genotype was associated significantly with diabetic retinopathy patients. All lipid profile parameters and plasma levels of E-selectin were significantly increased in diabetic patients; however, high-density lipoprotein cholesterol was significantly reduced in the diabetic patient group as a whole as well as in the diabetic retinopathy patient group. Conclusion The S128R (A561C) polymorphism of the E-selectin gene may be associated with diabetes mellitus but not with diabetic retinopathy, suggesting that the E-selectin gene polymorphism has no role as a predisposing factor for diabetic retinopathy. Such a hypothesis needs to be further confirmed by larger studies.