Pyrrolidine dithiocarbamate and saxagliptin ameliorate ulcerative colitis in rats

Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine (500 mg/kg), pyrrolidine dithiocarbamate (100 mg/kg), and saxagliptin (10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase (MAPK), phosphorylated extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), interleukin-12 (IL-12), caspase-3, β-defensin, inducible nitric oxide synthase (iNOS) and glucagon like peptide-1 (GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, iNOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and iNOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.

Interferon lambda 4 gene [IFNL4] linked to hepatitis c virus clearance, treatment

Background: A designated IFNL4 gene, encoding the interferon-X4 protein [IFNL4], which is moderately similar to IFNL3, is more strongly associated with HCV clearance in individuals of African ancestry, whereas it provides comparable information in Europeans and Asians

Aim of the work: The study was attempted for the identification of interferon Lambda 4 [IFNL4] gene expression in the liver biopsy and the recombinant IFNL4 protein in the serum of CHCV patients

Patients and methods: Eighty five patients with chronic hepatitis C virus infection [CHCV], whose age ranged between 19 and 57 years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before chronic HCV therapy, during the preparation of patients, and ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigations, CBCs. Liver biopsy was done to all patients and controls. Patients revealed mild fibrosis [Metavir fibrosis from Fl to F3]. Using freshly frozen liver biopsies to identify gene [IFNL4] by real time-PCR and the detection of its serum protein levels by EL1SA

Results: Patients with CHCV have higher hepatic expression of IFNL4 before treatment and also recombinant IFNL4 protein expression was detectable in serum with high levels

Conclusion: An inducible human protein-coding gene IFNL4, which is related to, known IFNs have been identified in genotype 4 CHCV patients

Recommendations: The therapeutic inhibition of IFNL4 might represent a novel biological target for the treatment of HCV and HBV infection and possibly other diseases

Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. METHODS: Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. RESULTS: This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). CONCLUSIONS: TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR.

role of vitamin D during therapy in chronic hepatitis C virus infection and its relation to CYP 27 B1-1260 promoter polymorphism

Objective: vitamin D is a potent immunomodulator. A number of genetic polymorphisms in the vitamin D pathway have been shown to affect vitamin D signaling, and stratification according to such polymorphisms has already being implemented in randomized controlled clinical intervention studies

Aim of the work: the study was attempted to examine whether vitamin D improved viral response and predicted treatment outcome in patients with chronic hepatitis C virus [CHCV] infection

Patients and methods: ninety two patients with CHCV, whose age ranged between 20 and 56 years, were selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, before and after the treatment with pegylated interferon [PEG-IFN], ribavirin [RBV] and vitamin D supplementation drops; 2000 IU/day, 10 drops/day, six patients whom received identical therapy without vitamin D were included to serve as controls. All the patients had body mass index [BMI]

Results: the treatment group with vitamin D had BMI

Conclusion: our study suggests a role of vitamin D in the response to treatment of chronic HCV patients. However, serum concentration is not a suitable predictor of treatment outcome. VDR had a predictive positive treatment outcome. CYP27B1-1260 was found to be an independent predictor of sustained virologic response [SVR]

Recommendations: The level of recommended supplementation of vitamin D depends on the patient's individual deficiency, although 2000 IU daily is a common dose. Patients taking vitamin D supplements should have serum measurements made after starting therapy to determine whether they are reaching target levels

fundamental role played by cell cycle proteins in controlling cell proliferation in chronic hepatitis C virus infection

Background: examining the alteration of cell cycle genes in early hepatitis C virus [HCV] found that altered expression of mitotic checkpoint genes, MAD2L1, KNTC1, CDC16 and CDC34, KNTC1 known as "rough deal protein" [ROD] is part of a complex involved in elaborating an inhibitory signal due to improper chromosomal aligment during cell division

Aim of the work: attempt for the identification of proteins [genes], which act as predictive factors to identify patients with high risk of cell transformation and HCC development

Patients and Methods: fifty three patients with chronic HCV infection, age ranged between 18 and 58 years, time of assessment was before starting therapy of hepatitis C at the National Hepatology and Tropical Medicine Research Institute. Ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography, and collection of blood samples for routine laboratory investigation; CBCs. Liver biopsy was done to all patients and controls, patients revealed mild fibrosis [Metavir fibrosis scores from F1 to F3]. Also, we used freshly frozen liver biopsies mRNA levels with perspective protein levels of four genes: P27, P15, KNTC1, MAD2L1

Results: significant association of P27, P15, KNTC1 and MAD2L-1 with the progression of liver fibrosis in chronic HCV liver biopsy was found

Conclusion: there is altered gene expression in HCV-associated liver disease

Recommendations: The emerging interest of hepatologists in the influence of genetic factors in HCV. Evaluation of the expression of key proteins related to the cell cycle and apoptosis in chronically infected patients with HCV would be of significance to understand disease pathogenesis, and will help in identifying novel prognostic indicators

IFN-stimulated genes upregulation pattern in Chronic Hepatitis C

Background: The development of effective tools for the large-scale analysis of gene expression has provided new insights into the involvement of gene networks and regular pathways in various disease processes. The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly on T cells that is activated by three ligands as follow: CXCL9 [Mig], CXCL10 [IP-10] and CXCL11 [I- TAC], and play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. Aim of the work: The study is a logical functional approach for the development of serum markers chemokines that bind to CXC chemokine receptor 3 to determine whether they play a role in the future of immune system to clear HCV, these chemokines: CXCL9, CXCL10 and CXCL11

Patients and methods: 131 male and female patients with chronic hepatitis C virus [CHCV] infection, their age ranges between 22 and 55 years,selected from the National Hepatology and Tropical Medicine Research Institute. The included patients were divided to two groups, the first group: 80 patients were investigated for the predictive values of CXCL9,10,11 and CXCR3 chemokines in peripheral blood mononuclear cells [PBMCs], the second group were fifty one patients analyzed for the expression of surface markers on CD8+T cells. Twenty healthy individuals were included to serve as controls for each group. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation and serological assay

Results: Chemokine CXCL9, CXCL10, CXCL11 and their receptor CXCR3 expression levels are induced in PBMCs during CHCV infection, associated with increased the expression levels of CD8+T cells in CHCV patients

Conclusion: The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection

Recommendations: The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver, the blocking of chemokines and chemokine receptor engagement is a therapeutic strategy that should be explored in the near future for non-responders to current anti-HCV therapy

Tumor necrosis factor-alpha [TNF - alpha] gene expression in chronic hepatitis B virus infection

Background: Tumor necrosis-alpha [TNF-alpha] is produced by macrophages, neutrophils, T-cells and NK-cells after stimulation. In turn, TNF-alpha can stimulate secretion, increase the expression of adhesion molecules as well as active neutrophils. Hence, it fulfills the role as a principal mediator of cellular immune response and inflammation, and may play an important role in non-cytopathic and cytolytic clearance of hepatitis B virus [HBV]. The clearance of HBV is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis [TNF-] gene promoter

Aim of the work: The study aimed to determine the TNF-alpha as a gene expressed in chronic hepatitis B virus infection and its role in outcome of the virus

Patients and methods: Ninety four patients with chronic HBV infection, their age between 19 and 59 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during treatment and twenty healthy individuals were included to serve as controls. All the patients and controls were subjected to the following; history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, and serological assay for HBsAg, HBsAb, HBeAg, HBeAb, HBV DNA [quantitative], and TNF-alpha promoter polymorphisms in two sites 238 and 308

Results: The prevalence of the variant at position -308 GA was similar in all investigated groups [patients and controls]. An association was found between the TNF-alpha promoter polymorphism at position -238 and the development of chronic HBV infection with sensitivity of 93% and specificity of 75%

Conclusion: TNF-alpha-308 GA was significantly associated with clearance, showing protective antibody and persistent HBV infection. The promoter variant of TNF-alpha at position 238 GA, GG appears to be linked to defective viral clearance, controls had higher TNF-alpha-238 GG,GA, AA as compared to cases with significant difference

Recommendations: The variation in the genes governing the levels of constitutive and inducible TNF-alpha might be an important factor, which might explain the variable outcome of HBV infection

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

<p><b>OBJECTIVE</b>To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis.</p><p><b>METHODS</b>Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected.</p><p><b>RESULTS</b>Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased.</p><p><b>CONCLUSIONS</b>The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).</p>

Can we use GP73 as a biomarker for the detection of hepatocellular carcinoma?

Hepatocellular carcinoma [HCC] is one of the top five leading causes of death in Egypt and its prevalence is increasing in the next 10-20 years. We aimed to detect the serum Golgi protein 73 [GP73] in patients with cirrhosis and with HCC, and to determine its sensitivity and specificity as a screening tool for the detection of HCC in this study. Serum GP73 was estimated in 93 participants [patients with HCC, patients with cirrhosis, and healthy controls]. GP73 was elevated in patients with HCC and liver cirrhosis; serum level was very high in HCC patients [P<0.01] when compared with the other studied groups. GP73 had sensitivity of 76%, specificity of 75%, at a cut-off value of 16.2 ng/ml with area under the receiver operator characteristic of 0.825 when compared with alpha-fetoprotein that showed a sensitivity of 63%, specificity of 43% at a cut-off value of 16.5 ng/ml and area under the receiver operator characteristic of 0.611. By combining alpha-fetoprotein and GP73 for the diagnosis of HCC, sensitivity and specificity were [93 and 25%], respectively. There is a significant positive correlation between diameter of the focal lesion and GP73 [P=0.01 and r=0.071]. Nonsignificant positive correlation was detected as regards serum GP73 and the number of HCC. GP73 can be used as a screening tool for the detection of HCC. Moreover, it shows a higher serum level with larger lesions

K469E polymorphism of the intercellular adhesion molecule-1 gene in Egyptians with coronary heart disease

The initial step in atherosclerosis is the adhesion of leukocytes to activated endothelial cells mediated by intercellular adhesion molecule-1 [ICAM-1]. This study aimed to investigate the association of K469E polymorphism of the ICAM-1 gene and soluble ICAM-1 [sICAM-1] serum level with coronary heart disease [HD] in Egyptian subjects. Using a case-control design, we studied 100 patients with CHD, including 73 patients with acute myocardial infarction [MI] and 27 with unstable angina [UA]. The control groups consisted of 50 healthy subjects with normal left ventricular function. All participants were genotyped for the ICAM-1 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Serum sICAM-1 was measured by enzyme-linked immunoassay [ELISA]. In CHD patients, the frequencies of K genotype [KK and EK] were significantly higher when compared to controls [P<.001] and were associated with an increased risk of disease development [OR=3.8, 95% CI: 1.7 to 8.5; P=.001]. K genotype frequencies in patients with MI showed no significant difference when compared to patients with UA [P=.121]. Serum sICAM-1 levels were comparable between CHD patients and controls [P=.37] and between MI and UA patients [P=.23]. There were no significant differences in sICAM-1 levels than women [P=.004]. ICAM-1 gene polymorphism in codon 469 is associated with a risk for CHD development in Egyptian subjects. Serum sICAM-1 is not influenced by this polymorphism and is not necessarily elevated in CHD

Correlation between level of soluble receptors of advanced glycated end products [sRAGE] and gene polymorphism of glycine 82 serine [G825] in patients with rheumatoid arthritis

Background: the receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA

Objective: to evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity

Methods: the study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine82serine [G82S] of the RAGE gene

Results: RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE

Conclusion: the levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine82serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions

Correlation between level of soluble receptors of advanced glycated end products [sRAGE] and gene polymorphism of glycine 82 serine [G82S] in patients with rheumatoid arthritis

The receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA. To evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity. The study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine 82 serine [G82S] of the RAGE gene. RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE. The levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine 82 serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions

effect of agents acting on NMDA and dopamine receptors on the responses of phrenic nerve-diaphram preparations from aged rats

Alzheimer's Dementia [AD] and Parkinsonism are common in geriatric patients. The skeletal muscles are important in the proper function of aging animals and humans. This study focuses on the influence of memantine [used for moderate to severe AD] and levodopalcarbidopa [LDICD] [a corner stone in the treatment of Parkinsonism] on responses of isolated phrenic nerve-diaphragms [IPNDs] of aged male rats. From 100 aged male albino rats twenty were untreated to study in vitro effects of memantine and LD/CD on 1PNDs. Eighty rats were divided into: Group-I [Control], Group II [oral meman tine, 1 .5mg/KgId], Group-Ill, [twice daily intraperitoneal LD/CD, 25/2.5mg/kg], Group-lV [both drugs]. After three weeks of treatment, animals were sacrificed; ten rats from each group were used to harvest IPNDs to study the effect of alIamine; 10 rats were used to measure nAchR [nicotinic acetyicholine receptor] alpha subunit mRNA by PCR. Heights of indirectly elicited contractions: 63.1 +/- 4, 6. 41.5 +/- 4.5, 70.6 +/- 4.7, 53.9 +/- 3.3mm for Groups I through IV respectively, all differences were statistically significant K0.05]. Memantine treatment caused a leftward shift of sallamine log-concentration-response curve, LD/CD caused ri.htward shift. Reversal of neuromuscular block required ier neostigmine concentrations in the memantine group it smaller concentrations in the LD/CD group. In Vitro m.antine inhibited diaphragmatic responses to indirect stam1ation. Values of nAchR alpha subunit mRNA [micro g/dl]: 1 +/- f116 [control], 0.13 +/- 0.11 [memnatine], 2.3 +/- 0.94 [LD/CD], 1.18 +/- 0.71 [both drugs] [p<0.05]. Memnatine inhibits neuromuscular transmission in vitro and with in vivo treatment. LD/CD treatment rtaaces neuiomuscular transmission. Clinical implications a1 further investigation

Effect of low calorie diet and exercise on thyroid hormones and leptin levels

To investigate the effect of low calorie diet alone and the effect of low calorie diet and exercise on the levels of thyroid hormones, leptin, and BMI. Also we tried to investigate if there is a relation between thyroid hormones and leptin levels. Two groups of normal male subjects, each group consists of 25 person matched for age and BMI. Group I had low calorie diet program for one month [1200-1500 Kcal]. Group II had the same low calorie diet in addition to program of therapeutic exercise on treadmill with moderate intensity every other day for one month. Evaluation of free T3, freeT4, TSH, leptin levels, and BMI were done before and after the study. Correlation between thyroid hormones and leptin levels were done. This study showed significant increase in Free T3, T4, and significant decrease in TSH, leptin and BMI after one month of low calorie diet program [group I] compared to their levels before the study. After one month of low calorie diet and the exercise program [group II], a highly significant increase in free T3, T4 and highly significant decrease in TSH, leptin and BMI compared to their levels before the study. Comparing the studied parameters of both groups after the study showed that there is a more significant increase in T3 and T4 and a more significant decrease in TSH and BMI in group II compared to group I. Leptin level showed no statistically significant difference. A positive correlation between BMI and leptin was found in both groups. We found no relation between thyroid hormones and leptin levels. Low calorie diet caused increase in the level of circulating thyroid hormones, and a decrease in TSH, leptin levels and BMI. Low calorie diet and moderate intensity therapeutic exercise caused more significant increase in the level of circulating thyroid hormones, more significant decrease in TSH level and BMI. No statistically significant difference in leptin level of both groups after the study. We found no relation between leptin level and thyroid hormone levels

Urinary monocyte chemoattractant protein-1 [MCP-1] correlates with prameters of renal injury in type II diabetes mellitus

Diabetic nephropathy [DN] is the leading cause of end stage renal disease in western world. Increased number of interstitial macrophages has been observed in biopsies from patients with DN. Monocyte chemoattractant protein-1 [MCP-1] is the strongest known chemotactic factor for monocytes and is upregulated in DN. We examined urinary level of MCP-1 in type 2 DM patients to assess the possible correlation between its level and the parameters of renal injury. Urinary MCP-1 level was assessed in 75 patients with type 2 DM [25 with and 25 without microabluminuria and 25 with macroalbuminuria and renal impairment] and compared with matched healthy control subjects. HBA1c and estimated glomerular filtration rate [eGFR] derived from the abbreviated Modification of Diet in Renal Disease [MDRD] equation were examined in the study groups in relation to the urinary MCP-1. urinary MCP-1 level was significantly higher in patients with micro and macroalbuminuria [167.4 +/- 50.23 and 630.87 +/- 318.10 ng/g creatinine respectively] as compared with normoalbuminuric patients and healthy controls [63.85 +/- 21.15 and 61.50 +/- 24.81 ng/g creatinine, p<0.0001]. MCP-1 correlated positively with urine albumin/creatinine ratio [ACR] [r=0.75, p<0.001], HBA1c [r=0.55, p<0.001] and inversely with eGFR [r=-0.60, p<0.001]. The study findings suggest that hyperglycemia is associated with increased urinary levels of MCP-1 that is closely linked to renal damage as reflected by proteinuria and eGFR levels. Collectively, these findings suggest that MCP-1 is involved in the pathogensis of diabetic nephropathy throughout its variable stages

modification of diet in renal disease [MDRD] equation underestimates glomerular filtration rate [GFR] in egyptian kidney donors

Inulin clearance and radioisotopic studies are the most accurate methods of GFR measurement, but are expensive. The K/DOQ1 guidelines recommended estimating GFR by using the Modification of Diet in Renal Disease [MDRD] or Cockcroft-Gault [CG] equations. So far, the MDRD equation has not been validated for GFR estimation in healthy donors. We examined the accuracy of the MDRD equation and creatinine clearance based on 24 hour urine collection in the prediction of GFR in a group of healthy donors in comparison with radionuclide measured GFR. We retrospectively examined the medical records of 100 of kidney donors who underwent [99M]Tc-diethylenetri amine-pentaacetic acid [DTPA] renal clearance and creatinine clearance at the transplant outpatient clinic, Cairo University Hospital between June 2002 and July 2006. GFR was predicted with the abbreviated MDRD formula without the variable for black. We examined the significant differences, potential correlations and agreements between the predicted and measured GFR. The mean eGFR [MDRD] was 8.16% lower than [99M]Tc-DTPA GFR [116.11 +/- 25.44 ml/ min/ 1.73 m[2] Vs. 126.32 +/- 24.21 ml/min/1.73 m[2], the difference range -84 to +61 ml/ min/ 1.73 m[2], p=0.002]. CrCl was 13.14% higher than [99M]Tc-DTPA GFR [142.90 +/- 27.51 ml/min 1.73 m[2], the difference range +65 to -60 ml/min/1.73 m[2], p<0.001]. A significant positive correlation was observed when CrCl and [99M]Tc-DTPA measured GFR were compared [r=0.451, r[2]=0.203, p=0.000]. No significant correlation was noted between eGFR MDRD and [99M] Tc-DTPA measured GFR [r=0.126, r[2]=0.016, p=0.211]. Linear regression analysis showed that at eGFR[MDRD] <99.37 ml/min/1.73 m[2], eGFR [MDRD] underestimated the DTPA GFR values. Bland Altman analysis showed poor agreement between GFR[MDRD] and CrCL on the one hand and measured GFR on the other hand [+54.2/-74.6 and +70/-36.8 respectively]. Our results indicate that neither MDRD equation nor CrCl are accurate in predicting GFR in healthy donors. Using MDRD in healthy individual might carry the risk of underestimating GFR in individuals with normal kidney function

Assessment of heme oxygenase-1 (HO-1) activity in the cavernous tissues of sildenafil citrate-treated rats / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To assess heme oxygenase-1 (HO-1) activity in the cavernous tissue of sildenafil citrate-treated rats.</p><p><b>METHODS</b>One hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor (zinc protoporphyrin, ZnPP); and group 4 received sildenafil and nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME). Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated.</p><p><b>RESULTS</b>In cavernous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO-1 cavernous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels (r = 0.646, r = 0.612 respectively; P < 0.001).</p><p><b>CONCLUSION</b>The actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.</p>

Effect of interferon: a on experimental schistosoma mansoni infection in mice

To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha on schistosomiasis, this cytokine was weekly injected into mice experimentally infected with S. mansoni, beginning from day 0 [group II], week 3 [group III], week 6 [group IV] and week 10 [group V] post-infection. TGF beta 1 serum levels were estimated on a weekly basis and beginning one week after initiation of IFN-alpha therapy, while all animals were sacrified on week 14 to be used for egg counts in liver and small intestine, oogram study for determination of the maturity of deposited eggs, and histopathological examination of stained liver sections. IFN-alpha treated groups were characterized by a more intense oviposition in the intestine [liver/intestine ratio less than 1], with higher egg numbers the earlier IFN-alpha was administered. Oograms of the intestine indicated the level of immature eggs to be statistically significantly higher in group II, III and IV than in the control group I [p < 0.05]. In IFN-alpha medicated mice, the mean numbers and diameters of hepatic granulomas were less than in GI, in addition to a lower representation of fibrocellular and fibrous granulomas among them [all parameters p < 0.05], especially in Gs IV and V. The inflammatory cell population in the form of eosinophils, histiocytes and giant cells was more pronounced in Gs III, IV and V. TGF-beta 1 serum levels showed a progressive rise, however more pronounced in the untreated control. A statistically positive significant was established between TGF-beta 1 levels and number, size and percentage of fibrotic hepatic granulomas in all groups

Assessment of nitric oxide and prostaglandins levels in different pathological types of glomerular disease

The objective of this study was to evaluate plasma nitrite and nitrate as well as urinary nitrite levels in forty cases with different glomerular disorders. In addition, serum thromboxane A2 [TXA2] and prostacyclin 12 [PGI2] levels were evaluated in these cases in comparison to 20 healthy control subjects. The effect of steroid therapy on the above mentioned parameters was also evaluated. The results revealed that urinary nitrite level was significantly elevated among patients compared to control. The elevation was observed in diabetic nephropathy as well as proliferative forms of glomerular disease such as lupus nephritis and mesangioproliferative GN. However, plasma nitrite, nitrate and serum cGMP levels were similar in patients compared to the control levels. TXA2 level exhibited significant elevation in patients, whereas serum PGI2 showed significant decrease in its level among cases as compared to control subjects. Steroid therapy was demonstrated to have no effect on all of the studied parameters. The study concluded that the data indicated that NO might play a role in the pathogenesis of proliferative glomerular disease and diabetic nephropathy. The demonstration of normal level of urinary nitrite in non proliferative GN suggests that enhanced NO production is not the sole cause of proteinuria in these cases. Further studies are, therefore, needed to examine the exact role of NO in pathogenesis of glomerular injury. The significant elevation of TXA2 level together with the significant decrease in serum PGI2 should be thoroughly investigated regarding the renal hemodynamics, the extent of proteinuria and the thromboembolic tendency reported in these cases

Serum levels of soluble CD40 ligand in patients with chronic and acute coronary syndromes and its relation to angiographic extent of coronary arterial narrowing

The aim of this study was to determine serum levels of soluble CD4O ligand [sCD4OL] in patients with chronic and acute coronary syndromes [ACS] and to assess the relation between sCD4OL levels and extent of coronary arterial narrowing in patients with ACS. Acute coronary events commonly result from thrombosis triggered by disruption of an atherosclerotic plaque. Recent studies have localized the receptor CD4O and its ligand in human atheroma. The CD4OL on activated T cells and platelets, by inducing the expression of matrix- degrading proteinases and of tissue factor procoagulant, may contribute to the triggering of acute coronary events. To study the role of CD4OL-CD4O interaction in coronary artery disease, we analyzed serum levels of sCD4OL in the peripheral blood from 10 patients with stable angina [SA]. 26 patients with unstable angina [UA], 22 patients with acute ST-segment elevation myocardial infarction [Ml] and 20 healthy controls by enzyme-linked immunosorbent assay [ELISA]. Coronary angiograms of all the VA patients and 18 Ml patients were reviewed to determine the culprit vessel [CV], CV complexity score [CVCS] [a score of I is given to a simple stenosis, 2: complex stenosis, 3: intracoronary thrombus, 4: total occlusion], type of CV lesion [A, B or C according to the lesion morphology] and vessel score [number of vessels with >/= 50% diameter stenosis]. Both patients with UA and Ml showed significantly higher levels of serum sCD4OL compared to patients with SA and controls; particularly high levels occurred in patients with UA [F ratio 34.9, p <0.001]. No statistically significant difference in sCD4OL levels was noted between VA and Ml patients or between SA patients and controls. Levels of sCD4OL did not show any significant correlation to peak CK. CK-MB in Ml patients or troponin T serum levels in UA patients. Levels of sCD4OL did not also show any significant correlation to CVCS, type of CV lesion or vesset score in VA or Ml patients. This study shows enhanced levels of sCD4OL levels in patients with UA and MI patients suggesting that CD4OL-CD4O interaction plays a pathogenic role in the triggering of ACS. Serum levels of sCD4OL could not however, predict the angiographic extent of coronary arterial narrowing