¿Cuál es el perfil de los pacientes en espera de nuevos tratamientos para la hepatitis C? / What is the Profile of Patients Waiting for New Hepatitis C Treatments?

Introducción: hasta hace poco, el tratamiento estándar de oro para la hepatitis C eran los interferones pegilados (Peg-IFN) en combinación con la ribavirina (RBV). Con la llegada de nuevos fármacos, se propuso evaluar los resultados del tratamiento y a los pacientes en espera de la nueva terapia. Materiales y métodos: este estudio analítico transversal evaluó el resultado del tratamiento en individuos con hepatitis C crónica, y luego comparó a individuos que tienen experiencia en no responder al tratamiento basado en interferón (IFN) con individuos sin experiencia de tratamiento previo. Resultados: el estudio incluyó 192 individuos. Entre 87 pacientes sometidos a tratamiento, se observaron bajas tasas de respuesta viral sostenida (RVS). La comparación de los 105 pacientes no tratados previamente y los 87 que habían recibido tratamiento con IFN previamente evidenció que entre los pacientes en espera de nuevas terapias, los individuos sin tratamiento previo presentaron mayor proporción de genotipo 1 (68% frente a 49%; p = 0,028), menores niveles de ALT (91,1 ± 73,0 frente a 126,0 ± 73,40 U/L; p = 017), de AST (70,1 ± 51,3 frente a 89,7 ± 47,40 U/L; p = 050), de GGT (85,3 ± 85,1 frente a 148,4 ± 123,9 U/L; p = 0,007) y menor proporción de fibrosis significativa (24,3 frente a 83,3; p <0,001). Conclusiones: las tasas de RVS fueron bajas. La mayoría de posibles candidatos para el tratamiento por VHC no lo han tenido y son de genótipo-1 con histología leve.

Introduction: Until recently, treatment with a combination of pegylated interferons (Peg-IFN) and ribavirin (RBV) was the gold standard treatment for hepatitis C. In anticipation of the arrival of new drugs, we evaluate current treatment outcomes and patients waiting for the new therapy. Materials and Methods: This cross-sectional analytical study evaluated treatment outcomes among chronic hepatitis C patients, and then compared chronic non-responders and treatment naïve patients who were given interferon based-treatment. Results: The study included 192 individuals among whom were 87 patients who received treatment. Among treated patients, we observed low rates of sustained viral response. A comparison of 105 treatment-naïve patients and 87 who had previously received IFN treatment showed that among patients waiting for new therapies, naïve individuals presented a higher proportion of genotype 1 (68% vs. 49%; p = 0.028) than did previously treated patients, lower ALT (91.1 ± 73.0 vs. 126.0 ± 73.40 U/L; p =017), lower AST (70.1 ± 51.3 vs. 89.7 ± 47.40 U/L; p = 050), lower GGT (85.3 ± 85.1 vs. 148.4 ± 123.9 U/L; p = 0.007) levels and a lower proportion of significant fibrosis (24.3% vs. 83.3%; p < 0.001). Conclusions: SVR rates were low. Among potential candidates for HCV treatment, the majority are naïve, genotype-1 with mild histology.

Correlation between location, size and histologic type of colorectal polyps at the presence of dysplasia and adenocarcinoma

Adenocarcinoma represents 96-98% of colorectal neoplasms, and neoplastic polyps (adenomas) are their precursors. The aim of this study is to correlate size, location and histologic type of colorectal polyps at the presence of dysplasia and adenocarcinoma. Methods: Colonoscopies from January/2007 to December/2008 were retrospectively studied, in order to evaluate the characteristics of the polyps. Results and Discussion: Out of the 2,401 analyzed colonoscopies, 583 (24.3%) presented polyps. Due to the lack of histopathologic data, 139 exams were excluded. Mean age of the patients was 58±12 years, and 60% were females. Polyps were prevalent in the left colon (38.5%) and rectum (32.5%). Out of the 850 polyps which were histologically examined, 55.17% were tubular adenomas; 21.88%, hyperplastic; 17.05%, serrated; 5.4%, tubulovillous; and 0.47%, villous. As to polyps ≤1.0 cm, dysplasia was observed in 16.0% and adenocarcinoma in 1.9%. Those >1.0 cm, 72.0% (p<0.001) presented dysplasia, and 25.3% (p<0.001) presented adenocarcinoma. Polyps in the right and transverse colon were strongly associated with dysplasia (17.8% and 16.7%). Adenocarcinomas were prevalent in the left colon (2.5%) and rectum (2.1%). Conclusion: Polyps were more frequent in the left colon and rectum. The right and transverse colons were strongly correlated with dysplasia. Those of the left colon and rectum were associated with adenocarcinoma. Lesions >1.0 cm were positively related to dysplasia and neoplasm. (AU)

O adenocarcinoma representa 96-98% do câncer colorretal, sendo os pólipos neoplásicos (adenomas) seus precursores. O objetivo desse estudo é correlacionar tamanho, localização e tipo histológico de pólipos colorretais com a presença de displasia e adenocarcinoma. Métodos: Estudou-se retrospectivamente colonoscopias realizadas entre janeiro/2007 e dezembro/2008, avaliando-se as características dos pólipos. Resultados e Discussão: Das 2401 colonoscopias analisadas, 583 (24,3%) apresentaram pólipos. Por falta de dados histopatológicos, excluiu-se 139 exames. A média de idade foi 58±12 anos, sendo 60% mulheres. Houve predomínio no cólon esquerdo (38,5%) e reto (32,5%). Quanto ao tamanho, 86,58% eram ≤1 cm. Dos 850 pólipos analisados histologicamente, 55,17% eram adenomas tubulares, 21,88% hiperplásicos, 17,05% serrilhados, 5,4% tubulovilosos e 0,47% vilosos. Dos pólipos ≤1,0 cm, 16,0% apresentaram displasia e 1,9% adenocarcinoma; dos >1,0 cm houve displasia em 72,0% (p<0,001) e adenocarcinoma em 25,3% (p<0,001). Pólipos do cólon direito e transverso associaram-se mais à displasia (17,8% e 16,7%, respectivamente). Adenocarcinoma predominou no cólon esquerdo (2,5%) e reto (2,1%). Conclusão: Os pólipos predominaram em cólon esquerdo e reto. Os do cólon direito e transverso correlacionam-se fortemente à displasia, e os do reto e cólon esquerdo ao adenocarcinoma. Lesões maiores que 1,0 cm associaram-se positivamente com a presença de displasia e neoplasia. (AU)

Identification of novel matrix metalloproteinase inhibitors by screening of phenol fragments library.

In the last 20 years, a great variety of synthetic, low molecular weight MMP inhibitors (MMPIs) have been synthesized and tested, although none has reached clinical utility. Exploration of novel ZBGs and development of non-hydroxamate MMPI has become a focus in current research. It's well-known that polyphenols can produce beneficial effects on human health by their antioxidant properties as well as they have the ability to block gelatinase activity. In this work we tested a series of selected phenols as MMP inhibitors. The most interesting hit (B6) shows sub-micromolar activity against MMP-2 (IC(50) 0.59 ± 0.05 µM, LE = 1.07) and a fairly good selectivity spectrum.

Biphenyl sulfonylamino methyl bisphosphonic acids as inhibitors of matrix metalloproteinases and bone resorption.

A number of matrix metalloproteinases (MMPs), proteins important in the balance of bone remodeling, play a critical role both in cancer metastasis and in bone matrix turnover associated with the presence of cancer cells in bone. Here, we report the synthesis and biological evaluation of a new class of MMP inhibitors characterized by a bisphosphonate function as the zinc binding group. Since the bisphosphonate group is also implicated in osteoclast inhibition and provides a preferential affinity to biological apatite, the new molecules can be regarded as bone-seeking medicinal agents. Docking experiments were performed to clarify the mode of binding of bisphosphonate inhibitors in the active site of MMP-2. The most promising of the studied bisphosphonates showed nanomolar inhibition against MMP-2 and resulted in potent inhibition of osteoclastic bone resorption in vitro.