Tackling Alzheimer's Disease with Existing Drugs:A Promising Strategy for Bypassing Obstacles

The unmet need for the development of effective drugs to treat Alzheimer's disease has been steadily growing, representing a major challenge in drug discovery. In this con-text, drug repurposing, namely the identification of novel therapeutic indications for approved or investigational compounds, can be seen as an attractive attempt to obtain new medications reducing both the time and the economic burden usually required for research and development programs. In the last years, several classes of drugs have evidenced promising beneficial effects in neurodegenerative diseases, and for some of them, preliminary clinical trials have been started. This review aims to illustrate some of the most recent examples of drugs reprofiled for Alzheimer’s disease, considering not only the finding of new uses for existing drugs but also the new hypotheses on disease pathogenesis that could promote previ-ously unconsidered therapeutic regimens. Moreover, some examples of structural modifica-tions performed on existing drugs in order to obtain multifunctional compounds will also be described

Apatinib for the treatment of gastric cancer

Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. AREAS COVERED: Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cance

Curcumin-1,2,3-Triazole Conjugation for Targeting the Cancer Apoptosis Machinery

The burden of neoplastic diseases is widely recognized as a severe cause of mortality. The clinical inadequacy of most anticancer therapeutics urgently prompted intense drug discovery efforts toward the identification of new chemical entities endowed with a potent and safe antitumor profile. In this scenario, targeting cancer cells apoptosis machinery has emerged as a relevant strategy, useful for tackling the emergence of drug resistance. On this basis, a small library of naturally inspired hybrid molecules was obtained by combining, through a click chemistry approach, "privileged" synthons such as curcumin scaffold and 1,2,3-triazole building block. Compound1, bearing apara-fluoro phenyl moiety, showed low-micromolar potency against T acute lymphoblastic leukemia cell growth. More in-depth biologic studies demonstrated, for this analog, cell death-inducing properties associated with its capability to simultaneously activate both the receptor and the mitochondrial apoptosis cascades. This peculiar behavior offers promises for achieving an expanded anticancer effect, namely intense cytotoxic response coupled with reduced predisposition of chemoresistance insurgence. Altogether, this study allowed the identification of compound1as a lead compound worth to be progressed as an anticancer drug candidate

Influence of cultivar and dipping pre-treatment on quality of minimally processed organically grown apples

Nowadays the demand for fresh or minimally processed fruits and vegetables is increasing but few have organic origin; among all fruits, fresh-cut apples are very much appreciated from the consumers. The aim of this work was to investigate the effect of an anti-oxidant treatment and the influence of cultivar on the quality of minimally processed organically grown apples during shelf-life. Cv Golden Delicious and cv Pink Lady were used, and the anti-oxidant treatment was carried out by dipping the apples in a solution of citric acid 1% and ascorbic acid 0.5%. After washing and core removing, apples were mechanically cut into 8 slices and dipped for 15 min-utes in the anti-oxidant solution. After draining, the excess water was dried with absorbing paper; then the apple slices were packaged in polythene boxes and stored at 3±1°C. Some slices were packaged without previous treatment as a control sample. Chemical and physical parameters were studied after 0, 2, 5 and 7 days of storage. Results showed that both cultivar could be used to obtain high quality fresh-cut products which can be stored at least for 7 days, and the antioxidant treatment had a positive effect in preserving apple characteristics

Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: Results of a large multicenter study involving 990 patients

Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients

Semiótica e história, fotografia e informação

¿Estamos preparados para producir contenido de imágenes para la sociedad de la ecología de los nuevos medios? El debate es necesario, tanto por parte de la academia como del mercado. El escenario ofrece algunas transformaciones que no se comprenden. Ocurren de forma natural. Esto sugiere que comprendemos las ideas de Neil Postman y Marshall McLuhan al definir el concepto de ecología de medios como el estudio de los medios como entornos. La preocupación de ambos se produjo en un momento médicamente conflictivo, considerando el desarrollo de la televisión a fines de la década de 1960 y la transformación social posterior. Marshall McLuhan, al escribir el libro Understanding Media, ya expresó su preocupación por reinterpretar la sociedad mediática al declarar que los medios interactúan entre sí. La radio ha transformado la forma de las noticias tanto como ha alterado la imagen en el cine sonoro. La televisión ha provocado cambios drásticos en la programación de radio, etc. Teniendo en cuenta estas inquietudes, organizamos el trabajo “Semiótica e historia, fotografía e información”, que aborda un debate sobre esta temática a partir de los conceptos de ecología de los medios. Este libro reúne los capítulos resultantes del I Congreso Internacional de Estudios de la Imagen y Ecología de los Medios, realizado por Ria Editorial y GENEM - Grupo de Estudio sobre la Nueva Ecología de los Medios. El congreso, realizado en modalidad 100% virtual, contó con el apoyo de DigiMedia - Centro de Investigación en Medios Digitales, Red INAV - Red Iberoamericana de Narrativas Audiovisuales y la Cátedra Latinoamericana de Narrativas Transmedia. Los textos están redactados en portugués o español, según el idioma de origen de los autores, o los países donde realizan sus investigaciones.http://wp.reno.com.br/index.php/semiotica-e-historia-fotografia-e-informacao

Low-Dose Oral Ethinylestradiol With Concomitant Low-Dose Acetylsalicylic Acid for Advanced Castrate-Resistant Prostate Cancer

BACKGROUND: The aim of the present study was to evaluate the activity and tolerability of low-dose oral ethinylestradiol (EE) and luteinizing hormone-releasing hormone analogue with concomitant low-dose acetylsalicylic acid (ASA) as a thromboprophylactic agent for advanced castrate-resistant prostate cancer (CRPC). PATIENTS AND METHODS: The patients received an EE dose of 150 \u3bcg daily (50 \u3bcg 3 times daily) and an ASA dose of 100 mg once daily. The primary endpoint was the prostate-specific antigen response. RESULTS: A total of 32 patients were enrolled. A PSA response was observed in 19 patients (59.3%; 95% confidence interval [CI], 41%-76%). The median progression-free survival was 9.4 months (95% CI, 6.5-14.1 months). The treatment was generally well tolerated and no grade 3-4 toxicity was observed. Only 1 patient interrupted EE because of a cardiac event and 1 patient experienced grade 2 nausea and vomiting. No major bleeding occurred. CONCLUSION: Low-dose EE with concomitant low-dose ASA is safe, showing potential activity in patients with advanced CRPC, and should be investigated furthe

Long-term results of the HD2000 trial comparing ABVD versus BEACOPP versus COPP-EBV-CAD in untreated patients with advanced hodgkin lymphoma: A study by fondazione Italiana Linfomi

Purpose The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPPEBV- CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. Wehere report a post hoc analysis of this trial after a median follow-up of 10 years. Patients and Methods Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). Results The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing secondmalignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). Conclusion With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC

The role of genetic factors in otitis media

É sabido que a otite média aguda pode ser causada por fatores ambientais, comofreqüentar creches, fumo passivo, curto período de amamentação e baixas condições sócio-eco-nômicas. A revisão das pesquisas recentes, contudo, sugere que fatores genéticos também contri-buem de forma significativa para a ocorrência da otite média aguda, recorrente e da otite médiacrônica, com efusão. Embora não existam estudos genéticos específicos, há consistentes evidên-cias em favor da transmissão genética de uma suscetibilidade para otite média. A história familiar,características raciais, a freqüência de antígenos HLA e de marcadores genéticos, entre outrosfatores, são algumas das evidências que serão apresentadas nesta revisão de literatura.It is well-known that otitis media can be caused by environmental factors, such asattending day care centers, passive smoking, early interruption of breast feeding, and unfavorablesocio-economic conditions. The review of current literature, however, suggests that genetic factorsalso contribute significantly to the occurrence of recurrent acute otitis media and otitis media witheffusion. Although there are no specific genetic studies, there is consistent evidence to support theidea of genetically transmitted susceptibility to otitis media. Family history, racial characteristics,HLA and genetic marker frequency are some of the topics discussed in the literature, which will bepresented in this review