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De novo renal allograft tumors were reported sporadically. Most of them were small, low-grade, and papillary renal cell carcinoma (RCC) type. A 46-year-old male presented with hematuria three decades after the first transplant. The patient had a history of three renal transplants. A tumor (12 cm × 13 cm) was diagnosed in the nonfunctioning first transplanted kidney. Radical nephrectomy of the graft harboring the tumor with preservation of the adjacent functioning graft was done and identified to be chromophobe RCC. After two-year follow-up, the patients had a perfect graft function with no evidence of oncological failure. We suggest that allograft tumor be considered in patient evaluation for hematuria. Regular follow-up imaging of transplanted kidney is mandatory even after graft failure for early detection of graft tumors.

Purpose: To identify the role of a set of microRNAs and their target genes and protein expression levels in the pathogenesis of bladder cancer with a muscular invasion (T2–T4) and non-muscular invasion (T1). Methods: In 157 patients, bladder specimen was examined for the expression of a set of miRNAs including let-7a-5p, miRNA-449a-5p, miRNA-145-3P, miRNA-124-3P, miRNA-138-5p, and miRNA-23a-5p and their targeted genes; β-catenin, WNT7A, IRS2, FZD4, SOS1, HDAC1, HDAC2, HIF1α, and PTEN using the qRT-PCR technique. The prognostic effect of miRNAs and their targeted genes on cancer-specific survival (CSS) was evaluated in pT2–pT4 stages. Results: pT1 was found in 40 patients while pT2–4 was found in 117 patients. The expression of let-7a-5P, miR-124-3P, miR-449a-5P, and miR-138-5P significantly decreased in pT2–4 compared with pT1 (p < 0.001), in contrast, miR-23a-5P increased significantly in pT2–pT4 compared with pT1 (p < 0.001). Moreover, the expression of miR-145 did not show a significant change (p = 0.31). Higher expression levels of WNT7A, β-catenin, IRS2, FZD4, and SOS1 genes were observed in pT2–pT4 compared with pT1, whereas HDAC1, HDAC2, HIF1α, and PTEN genes were downregulated in pT2–pT4 compared with pT1. Lower CSS was significantly associated with lower expression of let-7a-5P, miR-124-3P, miR-449a-5P, and miR-138-5P. Higher expression of β-catenin, FZD4, IRS2, WNT7a, and SOS1 was significantly associated with worse CSS. In contrast, lower levels of HDAC1, HDAC2, HIF1α, and PTEN were associated with lower CSS. Conclusion: Our results support let-7a-5P, miR-124-3P, miR-138-5P, and their target genes can be developed as accurate biomarkers for prognosis in bladder cancer with a muscular invasion.

Cisplatin is one of the most potent anti-cancer drugs used for the treatment of various solid tumors, yet it has several side effects that may limit its clinical use. Hepatotoxicity is one of the most serious side effects as it may lead to liver failure. Several mechanisms including oxidative stress, inflammation, and apoptosis have been examined in cisplatin-induced hepatotoxicity. Protocatechuic acid (Proto) which is naturally occurring phenolic acid has shown different biological activity as antioxidant, anti-inflammatory, and anti-apoptotic. In this study, we investigate the protective effect of Proto at two doses 100 and 150 mg/kg on hepatotoxicity induced by a single injection of 10 mg/kg cisplatin in female albino mice. The present study demonstrates for the first time that Proto administration (100 and 150 mg/Kg) significantly attenuates cisplatin-induced changes in liver function [increase serum albumin and decrease liver injury markers ALT, AST, GGT, and bilirubin]. This was associated with marked hepatic antioxidant effects [decrease MDA and NO levels, increase GSH and SOD activity]. Moreover, Proto reduced cisplatin-induced apoptosis in the liver through decreasing caspase-3, annexin-V, and BAX. Both doses suppressed cisplatin-induced expression of iNOS and NF-ᴋB p65 subunit and pro-inflammatory cytokines (IL-6 and TNF-α). Also, Proto improved histopathological examination of the liver. The present findings reveal that the antioxidant, anti-inflammatory, and anti-apoptotic effects of Proto are the main mechanisms by which Proto can ameliorate cisplatin-induced liver injury.

Hepatic damage is one of the most common complications related to cisplatin (Cis) use. Recently, liver protection lines are being discovered to avoid hepatic cell death as a result of oxidative, inflammatory, and apoptotic disturbance. Limited data reported the hepatoprotective effect of vinpocetine (Vin) in acute liver injury models. This study was designed to determine the potential protective effect of Vin (10-30 mg/kg, orally) against Cis-induced liver injury (10 mg/kg, IP) in mice. Vin administration for 1 week before Cis injection until the end of the experiment. On the 6th day after Cis injection, mice were anesthetized, blood and tissue samples were collected. Hepatic function, histological changes, oxidative stress, inflammation, and apoptotic markers were investigated. Vin administration ameliorated liver injury as indicated by decreased liver injury parameters; serum aminotransferases, ALK-P, GGT, and bilirubin, restored the anti-oxidant status by decrease MDA and NOx , and increased GSH and SOD, inhibited inflammation (IL-6, TNF-α, NFκB-p65, and iNOS) and apoptosis (Annexin-V, Bax, and Caspase-3) parameters. Vin confers dose-dependent protection against Cis-induced liver injury. The hepatoprotective effect of Vin involved anti-oxidative, anti-inflammatory, and anti-apoptotic activities.

To examine the prognostic effect of microsatellite instability (MSI) and loss of heterozygosity (LOH) on cancer-specific survival (CSS) in patients with muscle-invasive bladder cancer (MIBC).The liquid nitrogen-preserved specimens of 220 patients between March 2009 and December 2012 were analyzed for the presence of MSI and LOH in 12 loci (ACTBP2, D16S310, D16S476, D18S51, D4S243, D9S162, D9S171, D9S747, FGA, INF-α, MBP, MJD) using polymerase chain reaction. MSI was defined as MSI-stable, MSI-Low, or MSI-High if instability was detected in 0, 1, or 2 or more of the examined markers, respectively. The association between MSI-High and LOH and CSS was analyzed using uni- and multivariate analyses and the degree of agreement between tumor and urine samples were determined.MSI were found in 1030 (39%) and 1148 (43.5%) in tumor and urine specimens, respectively (Kappa = 0.77). On the other hand, LOH was found in 163 (6.2%) of tumor tissues and 44 (1.7%) in urine specimens (Kappa = 0.34). Microsatellite alterations were significantly associated with worse CSS at 1- and 5-year in tumor tissue (95% and 83.7% vs. 65.8% and 3.5%, respectively; P0.001) and in urine sample (90% and 64% vs. 46.5% and 9.3%, respectively; P0.001). MSI and/or LOH was an independent predictor of CSS (HR: 9.8; 95%CI: 5.1-18.9; P0.001).Microsatellite alterations were potentially an independent predictor of CSS in patients with MIBC. The agreement was good between tumor and urine MSI but weak for LOH.

Dancing compositions represented a large proportion of the works of many composers during the different musical eras in general and during the second half of the nineteenth century and the early twentieth century in particular, and took different names and were used to express feelings on many joyful and sad, emotional occasions And the avenue, patriotism and nationalism, and we find that the composer of dances is considered one of the musical compositions that are beloved by many pianists, especially college students, as many students prefer it to be within the content of his piano curriculum, and there are many studies that dealt with dances, where she indicated The study (Jehan Ezzat El Shafei, 2010) to Belgian dances and how to perform them, as well as the study (Amal Muhammad Talaat Ismail, 2010) that dealt with German dances according to Clara Schuman, but there is no single study that deals with the compositions of dancing and how they performed according to Harbert Holz. He composed a large number of dances that were distinguished by her distinguished musical style.

The present study aimed to determine the possible beneficial effects of dimethyl fumarate (DMF) against oxidative stress and inflammation in hypercholesterolemic rabbits. Twenty four New Zealand male rabbits were randomly allocated into 4 groups as the following: Group I (control): rabbits received standard rabbit chow; Group II high cholesterol diet (HCD): rabbits received 1% cholesterol-enriched chow for 4 weeks; Group III (HCD-DMF): rabbits received 1% cholesterol-enriched chow and administered DMF (12.5 mg/kg/day, orally) for 4 weeks; Group IV (DMF): rabbits received standard chow plus DMF (12.5 mg/kg/day, orally) for 4 weeks. At the end of experiment (day 30), blood samples were collected for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP). In addition, the aorta was removed for measurement of malondialdehyde (MDA), superoxide dismutase (SOD), mRNA expression of cholesteryl ester transfer protein (CETP) and histological assessment of intima/media (I/M) ratio. HCD-fed rabbits showed significant increases in TGs, TC, low-density lipoprotein cholesterol (LDL-C), aortic MDA and aortic I/M ratio levels while they significantly exhibited a reduced SOD level relative to control animals. Moreover, HCD rabbits demonstrated upregulated mRNA expression of CETP. DMF administration significantly decreased HCD-induced elevations in serum TC and LDL-C. Additionally, DMF decreased aortic level of MDA while increased SOD level. Moreover, DMF significantly downregulated mRNA expression of CETP and reduced the elevation in I/M ratio. In conclusion, this study suggests that DMF has the ability to improve HCD-induced vascular irregularities, possibly via its anti-inflammatory and antioxidant effect.

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Objectives To investigate the frequency and risk factors affecting the incidence of post-transplantation glomerulonephritis (GN) and the impact of GN on the survival of the graft and the patient. Patients and methods Patients were classified based on histological findings into three groups. Graft survival was ascertained using the Kaplan–Meier method and significance calculated using log-rank tests. For multivariate analysis the Cox model was used. Results Transplant glomerulopathy was the most prevalent glomerular disease in our series followed by recurrent GN and lastly de novo GN. In all, 50% of the de novo GN group had diabetes. The worst graft outcomes were in the recurrent GN group (P = 0.044). Multivariate analysis revealed ageing of the graft and mammalian target of rapamycin (mTOR) immunosuppression as risk factors for development of GN. While, the age of the recipient and donor, anti-lymphocyte globulin induction therapy, and acute rejection were risk factors for poor graft outcomes. Conclusions GN is an important issue after transplantation. Tracking the incidence and progression of histological findings in the graft may help to guide proper management and improve graft outcome.

The effects of cinnamaldehyde (CIN), a commonly consumed food flavor, against high-cholesterol diet (HCD)-induced vascular damage in rabbits were evaluated. Male New Zealand rabbits (n = 24) were allocated to four groups at random: control, fed with standard rabbit chow; CIN, fed with standard diet and administered CIN; HCD, fed with 1% cholesterol-enriched diet; and HCD-CIN, fed with HCD and treated with CIN. CIN was orally given at a dose of (10 mg/kg/day) concomitantly with each diet type from day 1 until the termination of the experimental protocol (4 weeks). HCD elicited significant elevations in serum levels of total cholesterol (TC), triglycerides (TGs), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively) compared with control rabbits. Moreover, aortic levels of nitric oxide metabolites (NOx) and antioxidant enzyme activities were significantly lower, while aortic levels of malondialdehyde (MDA) and myeloperoxidase (MPO) activity were significantly higher, in HCD-fed rabbits relative to control animals. CIN administration mitigated or completely reversed HCD-induced metabolic alterations, vascular oxidative stress, and inflammation. Moreover, CIN ameliorated HCD-induced vascular functional and structural irregularities. Aortic rings from HCD-CIN group showed improved relaxation to acetylcholine compared to aortas from HCD group. Moreover, CIN decreased atherosclerotic lipid deposition and intima/media (I/M) ratio of HCD aortas. CIN-mediated effects might be related to its ability to attenuate the elevated aortic mRNA expression of cholesteryl ester transfer protein (CETP) and MPO in HCD group. Interestingly, the vasculoprotective effects of CIN treatment in the current study do not seem to be mediated via Nrf2-dependent mechanisms. In conclusion, CIN may mitigate the development of atherosclerosis in hypercholestrolemic rabbits via cholesterol-lowering, antiinflammatory and antioxidant activities.

Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immunohistochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome.

This study investigates the possible protective effects of montelukast (MNT) against lipopolysaccharide (LPS)-induced cardiac injury, in comparison to dexamethasone (DEX), a standard anti-inflammatory. Male Sprague Dawley rats (160–180 g) were assigned to five groups ( n = 8/group): (1) control; (2) LPS (10 mg/kg, intraperitoneal (i.p.)); (3) LPS + MNT (10 mg/kg, per os (p.o.)); (4) LPS + MNT (20 mg/kg, p.o.); and (5) LPS + DEX (1 mg/kg, i.p.). Twenty-four hours after LPS injection, heart/body weight (BW) ratio and percent survival of rats were determined. Serum total protein, creatine kinase muscle/brain (CK-MB), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were measured. Heart samples were taken for histological assessment and for determination of malondialdehyde (MDA) and glutathione (GSH) contents. Cardiac tumor necrosis factor α (TNF-α) expression was evaluated immunohistochemically. LPS significantly increased heart/BW ratio, serum CK-MB, ALP, and LDH activities and decreased percent survival and serum total protein levels. MDA content increased in heart tissues with a concomitant reduction in GSH content. Immunohistochemical staining of heart specimens from LPS-treated rats revealed high expression of TNF-α. MNT significantly reduced percent mortality and suppressed the release of inflammatory and oxidative stress markers when compared with LPS group. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. MNT (20 mg/kg) was more effective in alleviating LPS-induced heart injury when compared with both MNT (10 mg/kg) and DEX (1 mg/kg), as evidenced by decrease in positive staining by TNF-α immunohistochemically, decrease MDA, and increase GSH content in heart tissue. This study demonstrates that MNT might have cardioprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and/or anti-inflammatory properties.

This study investigates the possible protective effects of levocetirizine against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150-200 g) were divided into 4 groups. Three groups were fed on high fructose diets (HFD) containing 60% w/w fructose, while the fourth control group was fed on standard laboratory food for 8 weeks. AUCOGTT, AUCITT, fasting glucose, HOMA-IR, hepatic glutathione (GSH) and malondialdehyde (MDA) levels, serum total cholesterol, LDL-C, C-reactive protein (CRP) level and lactate dehydrogenase (LDH) activity and liver steatosis scores were significantly higher in HFD group compared to control group. Moreover, body weight gain, food intake, feeding efficiency, HOMA-β, Emax and pEC50 of acetylcholine-induced relaxations of aortic rings and hepatic superoxide dismutase (SOD) activity were significantly lower in HFD group than in control group. Treatment with levocetirizine caused significant decreases in AUCOGTT, AUCITT, HOMA-IR, hepatic GSH and MDA levels and serum CRP level and LDH activity and significant increases in hepatic SOD activity and HOMA-β when compared with the HFD group. Although levocetirizine failed to alter TC and LDL-C levels, it produced a significant increase in HDL-C level relative to control group. Levocetirizine was also able to improve acetylcholine-induced relaxations of aortic rings, indicating a protective effect against insulin resistance-induced endothelial damage comparable to that offered by pioglitazone. Moreover, levocetirizine substantially attenuated insulin resistance-associated liver macrovesicular steatosis. These findings demonstrate that levocetirizine ameliorates insulin resistance, improves glucose tolerance and attenuates insulin resistance-linked hepatic steatosis and vascular damage.

Background: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. Methods: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. Results: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. Conclusion: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

What's known on the subject? and What does the study add? It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney. OBJECTIVE • To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney. METHODS • Male mongrel dogs (n= 32) were classified into three groups: sham (eight), control (12) and study (12). • A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO. • Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction. • Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment. RESULTS • Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction. • In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD. • Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction. CONCLUSION • Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.

The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

Objectives To assess the predictive importance of ultrasonic grade 1 hyperechogenicity in potential live related kidney donors in the absence of urinary abnormalities and with perfect renal function.

Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 +/- 367.1 Pg/ml) compared to those with inactive disease (441.33 +/- 225.19 Pg/ml) and the healthy control volunteers (111.5 +/- 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied.

Systemic lupus Erythematosus (SLE) is a rheumatic autoimmune disease characterized by multisystem organ involvement and by high titers of auto antibodies against several nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network have been described in patients suffering from SLE. However the role of cytokines in different organ involvement is not yet well defined.To determine if levels of Interlukin-6 (IL-6) and Tumor necrosis factor (TNF-alpha) correlate with SLE disease activity in Egyptian SLE patients and more specifically with hematological involvement.Levels of TNF-alpha and IL-6 in serum samples from sixty individuals (40 with Systemic lupus Erythmatosus and 20 healthy controls) were determined and renal biopsies were obtained from SLE patients.Levels of TNF-alpha and IL-6 were higher in SLE patients with active compared with inactive hematological disease. Further analysis showed that this association was dependent on inverse correlation (P=0.017, r=-0.49) for IL-6 and (P=0.76, r=-.243) for TNF-alpha. The mean level of TNF-alpha and Il-6 was (766.95+/-357.82 pg/ml) and (135.4+/-54.23 pg/ml) respectively for patients with active disease while it was (314.01+/-100.87 pg/ml) and (47.33+/-18.61 pg/ml) for those with inactive disease and (172.7+/-39.19 pg/ml) and (21.15+/-10.99 pg/ml) for the healthy control group respectively. The difference was statistically significant (P=0.002). We found significant positive correlations between TNF-alpha and IL-6 and the SLE Disease Activity Index (SLEDAI) score. (r=+0.743 and +0.772 respectively).Raised level of Il-6 and TNF-alpha may influence the development of anemia in Egyptian patients with Lupus Nephritis.

In this study, we studied the effect of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), an inhibitor of Toll-like receptor 4 (TLR4), in LPS-induced acute lung injury (ALI). Male Sprague–Dawley rats were treated with LPS-RS (0.1 mg/kg body mass, by intraperitoneal (i.p.) injection) 1 h before LPS injection (10 mg/kg, i.p.). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected 24 h later to determine total and differential cell count, total protein content, levels of lactate dehydrogenase (LDH), histopathological changes, markers of oxidative stress, and mRNA expression of the inhibitory protein nuclear factor kappaB-α (NFκBIA) and TLR4. Additionally, rings of pulmonary artery were isolated for measuring vascular reactivity. LPS-induced ALI was indicated by increases in total and differential cell count, total protein, and LDH in BALF, and increased lung levels of malondialdehyde (MDA), as well as decreased activity of reduced glutathione (GSH) and superoxide dismutase (SOD). Moreover, LPS increased pulmonary artery contraction in response to phenylephrine (PE). Additionally, LPS downregulated mRNA expression of NFκBIA and upregulated mRNA expression of TLR4. LPS caused a marked inflammation in the lung tissue, with tubercular granuloma and numerous neutrophils. Pretreatment with LPS-RS protected against LPS-induced ALI by decreasing total and differential cell count, total protein, and LDH in BALF, and increased pulmonary GSH content and SOD activity without affecting MDA content. Additionally, it decreased the elevated PE-induced pulmonary artery contraction. LPS-RS upregulated mRNA expression of NFκBIA and downregulated mRNA expression of TLR4. Moreover, LPS-RS prevented inflammation in lung tissues. In conclusion, pretreatment with LPS-RS protects against LPS-induced ALI in rats through its anti-inflammatory effects, possibly by decreasing the mRNA expression of TLR4 and increasing that of NFκBIA.

Background In view of the high cost of the new immunosuppressive drugs, which represents a challenge for both patients and governmental resources especially in developing countries, trials to prevent side effects of the first calcineurin inhibitor discovered (cyclosporine, Cs) are of particular interest. Methods In this prospective randomized experimental study, 60 male Sprague Dawley rats were enrolled. Group 1 served as negative control group and received olive oil. Group 2 received Cs orally 100 mg/kg for 80 days and served as positive control group. Group 3 was given daily colchicine (30 μg/kg/day) in addition to Cs. Group 4 was given omega-3 fatty acids (100 mg/kg/day) in addition to Cs. Animals were subjected every other week to laboratory assessment for serum creatinine, sodium, potassium, and Cs whole-blood through levels. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. Results There were no significant differences in serum creatinine, creatinine clearance, and serum sodium and potassium in all groups. Histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner strip of the outer medulla in all Cs-treated animals. Morphological changes were significantly less in colchicine-treated rats compared to omega-3 fatty acid–treated rats and absent in the negative control group. Furthermore, immunostaining showed positive reactions for vimentin in Cs-treated animals only. Conclusions Colchicine and omega-3 fatty acids are protective for the kidney against cyclosporine-induced nephropathy; however, colchicine is more protective than omega-3 fatty acid.

Development of late uro-intestinal malignancy after bowel incorporation into the urinary tract is a constant long-term hazard, even in the absence of fecal material. We report 6 such cases.A total of 350 patients treated with an ileal conduit, 260 with ileal replacement of the ureter and 55 with ileocystoplasty were evaluated and followed for a minimum of 4 years. The methods of evaluation included urine analysis for microscopic hematuria, urine culture, serum creatinine and abdominal ultrasonography. These evaluations were performed every 2 months after cystectomy for bladder cancer and every 6 months in other cases. Annual urinary cytology and excretory urography were done. Computerized tomography and/or magnetic resonance imaging was performed annually after radical cystectomy or if there was evidence of hematuria, ureteral obstruction or a filling defect in the bladder, pouch or conduit on excretory urography. Endoscopic evaluation was done in some cases. If malignancy was diagnosed chest x-ray and bone scintigraphy were performed.A total of 645 patients were evaluable. Of these patients late cancer developed at the uro-intestinal anastomotic site in 6 (0.9%), including 1 of 348 (0.3%) who underwent ileal conduit, 3 of 54 (5.5%) ileocystoplasty and 2 of 258 (0.8%) ileal replacement of ureter. The latent period "from the time of original surgery till the development of cancer" ranged from 4 to 32 years (mean plus or minus standard deviation 20.2 +/- 10.9). The pathological type of cancer was adenocarcinoma in 3 patients, transitional cell carcinoma 2 and squamous cell carcinoma 1.Late uro-intestinal malignancy in patients who underwent ileal incorporation in the urinary tract is a low but still distinct risk. Ileocystoplasty is more vulnerable to late uro-enteric cancer than ileal conduit and ileal replacement of ureter. Late malignancy can develop earlier than 10 years postoperatively. Therefore, annual surveillance by routine urine cytology postoperatively is advocated, particularly with enterocystoplasty.

This study was undertaken to examine the effects of montelukast (MNT) on lung and kidney injury in lipopolysaccharide (LPS) induced systemic inflammatory response. Rats were randomized into 5 groups (n = 8 rats/group): (i) Control; (ii) LPS treated (10 mg/kg body mass, by intraperitoneal (i.p.) injection); (iii) LPS + MNT (10 mg/kg, per oral (p.o.)); (iv) LPS + MNT (20 mg/kg, p.o); (v) LPS + dexamethasone (DEX; 1 mg/kg, i.p.). Twenty-four hours after sepsis was induced, the lung or kidney:body mass ratio and percent survival of rats were determined. Creatinine, blood urea nitrogen (BUN), albumin, total protein, and LDH activity were measured. Lung and kidney samples were taken for histological assessment and for determination of their malondialdehyde (MDA) and glutathione (GSH) contents. The expression of tumour necrosis factor α (TNF-α) in tissue was evaluated immunohistochemically. LPS significantly increased the organ:body mass ratio, serum creatinine, BUN, and LDH, and decreased serum albumin and total protein levels. MDA levels increased in lung and kidney tissues after treatment with LPS, and there was a concomitant reduction in GSH levels. Immunohistochemical staining of lung and kidney specimens from LPS-treated rats revealed high expression levels of TNF-α. MNT suppresses the release of inflammatory and oxidative stress markers. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. These results demonstrate that MNT could have lung and renoprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and (or) anti-inflammatory properties.

Objectives Thin basement membrane disease (TBMD) or benign familial hematuria is common in women. The median age is 37 years among adults. About two-third of the patients with TBMD have at least one other hematuric family member when five relatives are tested. Case report We hereby present a case of adult TBMD to clarify the clinicopathological characteristics of the disease in 56-year-old woman with long-standing intermittent dark colored urine with proteinuria, normal serum creatinine, and with normal blood pressure. Renal pathology showed normal renal tissue by using the light and immunofluorescence examination. Thinning of the glomerular basement membrane, ranging from 110 to 200 nm, was demonstrated by using electron microscopy. Conclusion Although it is part of routine nephropathology worldwide, electron microscopic examination of renal biopsies are rarely used in Egypt. This important diagnostic pillar should be more frequently used among our patients, especially when clinicopathologic diagnosis is unclear.

INTRODUCTION AND OBJECTIVES: To identify the prognostic role of lymph node density (LN-d) in a single series of patients undergone RC and to validate findings on an external series. METHODS: Between May 1998 and September 2009 data of 1084 Radical Cystectomies performed at two Institutes were collected in a prospectively-maintained database. After applying selection criteria (neither neoadjuvant nor adjuvant treatments, not salvage cystectomies) 979 out of 1084 patients (695 pN0 and 284 pN ) with non-metastatic bladder carcinoma were selected. The external validation of findings was performed on a single-centre series of 775 patients (590 pN0 and 185 pN ) with the same selection criteria. All patients underwent RC and pelvic lymphnode dissection (PLND). Once lymph node density (LN-d) and lymphnode count (LN-c) cut-off values were identified by maximally selected Log-rank analysis, the prognostic role of several variables on diseasefree survival (DFS) was assessed with univariable and multivariable Cox regression analyses. RESULTS: Statistically significant variables at univariable analysis were histological subtypes (p 0.001) [squamous cell carcinoma (SCC), urothelial carcinoma (UC), urothelial carcinoma with squamous differentiantion (US), adenocarcinoma (AC)], pT (p 0.001), pN (p 0.001), LN-d (p 0.001), PLND extent (p 0.001). At stepwise Cox regression analysis on the internal series of 979 patients pT (p 0.001), LN-d (p 0.001), extent of PLND (p 0.001) and histological subtypes (p 0.001) were independent predictors of DFS (Table 1). On the external cohort of 775 patients pT (p 0.001), LN-d (p 0.001) and histological subtypes (p 0.035) proved to have independent role on DFS (Table 1). CONCLUSIONS: LN-d thresholds identified in the internal cohort were independent predictor of DFS in the external validation cohort. LN-d, pT stage and histological subtypes were the only independent prognostic factors in both series.

What's known on the subject? and What does the study add? It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney.To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney.Male mongrel dogs (n = 32) were classified into three groups: sham (eight), control (12) and study (12). A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO. Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction. Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment.Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction. In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD. Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction.Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.

OBJECTIVES To investigate possible associated pathology in the prostate removed from patients with invasive bladder cancer and determine if there is a justification for prostate-sparing cystectomy. PATIENTS AND METHODS Between March 2005 and July 2007, 425 men (mean age 59 years, sd 8.23) had a cystoprostatectomy at our institute. The prostate was step sectioned at 2–3 mm intervals and any associated pathology determined; patient and tumour characteristics were correlated with prostatic pathology. The results were compared with those published previously, and the potential functional advantages of prostate sparing are reviewed and discussed. RESULTS Prostatic adenocarcinoma was detected in 90 of the 425 (21.2%) patients. There was no significant correlation between preoperative prostate-specific antigen level and the presence of adenocarcinoma, Gleason score or prostatic tumour stage. There was prostatic involvement as a result of direct invasion by the primary bladder tumour (contiguous) in 39 cases (9.2%). Concomitant (non-contiguous) transitional cell carcinoma of the prostatic urethra and/or ducts was detected in 27 specimens (6.4%). Additional findings were high-grade prostatic intraepithelial neoplasia in 43 patients (10.1%) and benign prostatic hyperplasia in 175 (41.2%). CONCLUSION We think that the potential oncological risks of prostate-sparing cystectomy outweigh any small and possible functional benefits; accordingly, the prostate should not be retained.

SUMMARY: Background: Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE) and the mechanism of atherogenesis remains poorly understood. Low-grade inflammation and endothelial dysfunction play pivotal roles in the initiation, progression and propagation of the atherosclerotic process. Several methods have been employed to assess endothelial function, among them the measurement of biomarkers of endothelial activation and dysfunction (intercellular adhesion molecule (ICAM)-1). Since then, it has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. Objective: To measure (tumour necrosis factor (TNF)-α, interleukin (IL)-6 and ICAM-1) levels as markers of inflammation and atherosclerosis in 40 Egyptian patients with SLE with various degrees of activity in comparison with 20 healthy volunteers, and to investigate their relationship to disease activity and hypertension. Methods: Sixty subject (40 with SLE and 20 healthy controls) were the subject of this study, their clinical disease activity was scored according to the SLE Disease Activity Index (SLEDAI), and serum sampling was obtained for TNF-α, IL-6 and ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy. Results: The mean level of TNF-α, IL-6 and ICAM-1 were significantly higher in SLE patients with active disease (766.95 ± 357.82 Pg/mL, 135.4 ± 54.23 Pg/mL, 826.05 ± 367.1 Pg/mL) when compared with those with inactive disease (314.01 ± 100.87 Pg/mL, 47.33 ± 18.61 pg/mL, 441.33 ± 225.19 Pg/mL) and healthy control volunteers (172.7 ± 39.19 Pg/mL, 21.15 ± 10.99 Pg/mL, 111.5 ± 17.36 Pg/mL), respectively. Furthermore, these levels were significantly higher in hypertensive (614.08 ± 333.05 Pg/mL, 107.86 ± 54.96 Pg/mL and 862.13 ± 333.29 Pg/mL) compared to normotensive patients (267.5 ± 112.72 Pg/mL, P = 0.008, 35.75 ± 20.26 Pg/mL, P = 0.02I, and 337.25 ± 235.62 Pg/mL, P = 0.02) for TNF-α, IL-6 and ICAM, respectively. There were no statistically significant difference regarding age, sex, smoking, cholesterol and high-density lipoprotein (HDL) levels between hypertensive and normotensive patients. Conclusion: A high concentration of soluble ICAM-1 in Egyptian patients with SLE and nephritis is reported here for the first time. Our finding of increased concentrations of TNF-α, IL-6 and ICAM-1 in Egyptian patients with SLE and lupus nephritis underlines the importance of inflammation and endothelial involvement in this disorder, but their predictive value in the disease monitoring needs to be further studied.

We prospectively studied the pathological outcome and incidence of urethral recurrence after radical cystectomy and orthotopic bladder substitution in women.Between January 1995 and December 2001, 145 women with a mean age of 50 +/- 8.5 years underwent standard radical cystectomy and orthotopic substitution for bladder cancer. Histopathological examination of the cystectomy specimens was assessed by a single pathologist. Clinically evident pelvic lymphadenopathy, bladder neck and/or vaginal wall involvement, or positive intraoperative frozen section from the urethra were considered contraindications.One patient died postoperatively of a massive pulmonary embolism. Followup was 12 to 97 months (mean 36, median 55.8). Pathological stage was P1, P2 (superficial muscle invasion), P3a (deep muscle invasion), P3b (perivesical fat infiltration) and P4a in 12, 29, 56, 44 and 4 patients, respectively. Grade was G1 in 61 patients, G2 in 62 and G3 in 22. Lymph nodes were positive in 28 cases and negative in 117. Histopathology of the trigone revealed carcinoma in situ in 11 cases and squamous metaplasia in 7, while results were free of disease in the remainder. At followup isolated urethral recurrence developed in 2 patients (1.4%), in whom definitive pathological findings showed P3a N1 (positive iliac lymph nodes) M0, grade 2 squamous cell carcinoma in 1 and P3b N0M0 tumor associated with trigonal carcinoma in situ in 1. Local pelvic recurrence developed in 18 patients, distant metastasis developed in 6 and the 2 conditions developed in 10. Oncological failure positively correlated with high stage, high grade and positive lymph nodes.The rate of urethral recurrence after radical cystectomy and orthotopic bladder substitution in women is low and acceptable and, thus, it justifies the continued performance of this type of diversion. Proper selection of cases is mandatory. Close followup for oncological failure in this group of patients after cystectomy is necessary.