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Exp Clin Transplant ; 17(6): 823-827, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29534659


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.

Naunyn Schmiedebergs Arch Pharmacol ; 391(11): 1203-1219, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30058017


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.

Acroleína/análogos & derivados , Hipercolesterolemia/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/fisiologia , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol/genética , Colesterol na Dieta/administração & dosagem , Regulação da Expressão Gênica , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Masculino , Óxido Nítrico/metabolismo , Peroxidase/genética , Peroxidase/metabolismo , Substâncias Protetoras/farmacologia , Coelhos , Triglicerídeos/sangue
Arab J Urol ; 13(4): 295-305, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26609451


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.

Can J Physiol Pharmacol ; 92(10): 839-47, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25243774


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.

Acetatos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Quinolinas/farmacologia , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Acetatos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Peso Corporal , Rim/patologia , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Quinolinas/uso terapêutico , Distribuição Aleatória , Ratos Sprague-Dawley , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/patologia
BJU Int ; 110(6): 904-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22381210


UNLABELLED: 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.

Ácidos Cumáricos/farmacologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Obstrução Ureteral/complicações , Animais , Cães , Rim/anormalidades , Masculino
Int Urol Nephrol ; 38(3-4): 731-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17260180


BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Raised level of Il-6 and TNF-alpha may influence the development of anemia in Egyptian patients with Lupus Nephritis.

Interleucina-6/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/sangue , Nefrite Lúpica/complicações , Fator de Necrose Tumoral alfa/sangue , Adulto , Egito , Feminino , Humanos , Masculino