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Naunyn Schmiedebergs Arch Pharmacol ; 392(12): 1591-1604, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31367864


Hepatocellular carcinoma (HCC) is characterized by bad prognosis and is the second most common reason for cancer-linked mortality. Treatment with sorafenib (SRF) alone increases patient survival by only a few months. A causal link has been determined between angiotensin II (Ang-II) and HCC. However, the mechanisms underlying the tumorigenic effects of Ang-II remain to be elucidated. N-Nitrosodiethylamine was utilized to examine the effects of telmisartan (TEL) (15 mg/kg), SRF (30 mg/kg), and a combination of these two agents on HCC mice. Downregulation of NF-кBP65 mRNA expression and inhibition of the phosphorylation-induced activation of both ERK1/2 and NF-кB P65 were implicated in the anti-tumor effects of TEL and SRF. Consequent regression of malignant changes and improvements in liver function associated with reduced levels of AFP, TNF-α, and TGF-ß1 were also confirmed. Anti-proliferative, anti-metastatic, and anti-angiogenic effects of treatment were indicated by reduced hepatic cyclin D1 mRNA expression, reduced MMP-2 levels, and reduced VEGF levels, respectively. TEL, but not SRF, demonstrated agonistic activity for PPARγ receptors, as evidenced by increased PPARγ DNA binding activity, upregulation of CD36, and HO-1 mRNA expression followed by increased liver antioxidant capacity. Both TEL and SRF inhibited TAK1 phosphorylation-induced activation, indicating that TAK1 might act as a central mediator in the interaction between ERK1/2 and NF-кB. TEL, by modulating the ERK1/2, TAK1, and NF-кB signaling axis in the context of PPARγ agonistic activity, exerted anti-tumor effects and increased tumor sensitivity to SRF. Therefore, TEL is an encouraging agent for further clinical trials regarding the management of HCC.

Reumatol Clin ; 2018 Aug 27.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30166230


OBJECTIVES: To investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients. PATIENTS AND METHODS: This study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection. RESULTS: The NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9. CONCLUSION: NLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging.

Urology ; 96: 80-84, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27417920


OBJECTIVE: To characterize the standard physical, chemical, and microscopic characteristics of urine in patients with noncomplicated orthotopic ileal neobladders. MATERIALS AND METHODS: This is a prospective study that included 100 male patients who underwent radical cystectomy and ileal neobladder between 1993 and 2013. All included patients were in a good health and having satisfactory function of the reservoirs with normal upper tract with a minimum 1-year postoperative follow-up. We excluded patients with oncological failure, those with diversion-related complications, those who were maintained on clean intermittent catheterization, or those who have symptoms of urinary tract infection. Patients with medical diseases that may affect urine properties (eg, diabetes mellitus) or receiving special medications (eg, diuretics, alkali therapy, or antibiotics) were also excluded. The patients were subjected to urine analysis, blood chemistry, pH, and blood gases; the results were compared to a control group of 40 normal male volunteers. RESULTS: Urine analysis in diverted patients showed higher urine pH than in control group but it is still acidic. Pyuria, proteinuria, hematuria, and positive culture were significantly higher in diverted patients. The chemical analysis showed lower urinary calcium, phosphorus, and creatinine contents in diverted patients than in the control group. Serum creatinine was significantly higher in diverted patients, whereas blood pH and bicarbonate were lower, but these values are within normal. CONCLUSION: Urine from uncomplicated orthotopic ileal reservoirs is acidic. Pyuria, proteinuria, minor degrees of microscopic hematuria, and positive nitrite reaction are normal findings. We also have normal findings for lower urinary calcium, phosphorus, and creatinine contents in patients.

Cistectomia , Íleo/transplante , Complicações Pós-Operatórias/urina , Neoplasias da Bexiga Urinária/cirurgia , Coletores de Urina , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Urinálise/métodos