RESUMEN
OBJECTIVE: Diabetic nephropathy (DN) represents the most common cause of end-stage renal disease. On the other hand, Bone Morphogenetic Protein signaling pathway (BMP/Smad) is one of the most interesting prophylactic targets, since inhibition of this pathway may preserve kidney functions. Therefore, a BMP pharmacological inhibitor, Dorsomorphin Homolog 1 (DMH1) was used to assess the potential nephroprotective effect in an animal model of DN. MATERIALS AND METHODS: STZ-induced diabetic rat was the selected model to assess the nephroprotective effect of DMH1(5 mg/kg) for eight weeks. Rats were divided into normal control (C=10), diabetic control (DC=10), diabetic+vehicle (DV=10) and diabetic DMH1-treated rats (DT=10). Fasting blood glucose (FBG) level was measured on a weekly basis. Then, glycated hemoglobin (HbA1c), serum Creatinine (sCr), Cystatin-C (Cys-C) and Blood Urea Nitrogen (BUN) were measured by the end of the experiment. Furthermore, Tumor Necrosis Factor (TNF-α), Interleukin-6 (IL-6) and Malondialdehyde (MDA) levels were determined in kidney tissues. The histopathological study was also performed using Hematoxylin and Eosin (H&E), Periodic acid Schiff (PAS) and Masson's trichrome stains. RESULTS: DMH1 treatment has significantly reduced HbA1c along with sCr, Cys-C and BUN vs. the diabetic non-treated groups (p < 0.001). Furthermore, TNF-α, IL-6 and MDA levels were also significantly decreased in the DT group compared to the diabetic non-treated groups (p < 0.001). This improvement was further confirmed and found in correspondence with histopathological findings. CONCLUSIONS: The present findings revealed a nephroprotective activity of DMH1 against STZ-induced DN in rats. DMH1 also showed anti-inflammatory and antioxidant activities, which may explain part of the nephroprotective mechanism. This can shed light on the importance of DMH1 and BMP/Smad pathway for further experimental studies.
Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Animales , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/prevención & control , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Interleucina-6/metabolismo , Riñón/patología , Masculino , Pirazoles , Pirimidinas , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Background: Exposing patients with metastatic colorectal cancer (mcrc) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy. Methods: The medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance. Results: Of the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (ps) of 1 in 16 patients, ps 2 in 3, ps 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of xelox or folfox in 13 patients, xeliri or folfiri in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (ci): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% ci: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% ci: 2.4 months to 9.6 months), and overall survival was 15 months (95% ci: 9.6 months to 20.4 months). Conclusions: Second-line chemotherapy after first-line triplet therapy in mcrc is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/farmacología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
A 2 days old, 2.7 kg heavy baby boy with critical pulmonary stenosis, underwent successful balloon dilation. After the uneventful procedure, he remained oxygen dependent. The baby was given oral angiotensin converting enzyme inhibitor (ACE inhibitor), instead of an infusion of alpha blocker. Within few hours, in the afternoon of the same day after administration of ACE Inhibitor, the baby could be weaned off oxygen, maintaining on room air, oxygen saturation between 87% and 92%. At follow-up, two months later, his saturation was 99% on room air. We believe that some neonates with critical pulmonary valve stenosis who remain oxygen dependent despite successful balloon dilation, could benefit from such management.