Present and future pharmacotherapy for benign prostatic hyperplasia

Around 50% of men 51-60 years of age have pathological benign prostatic hyperplasia (BPH). Pharmacotherapy for BPH includes the 5alpha-reductase inhibitor finasteride, and alpha(1)-adrenoceptor antagonists. Finasteride reduces prostate volume and symptom scores, while increasing peak urinary flow rates. The main problem with finasteride treatment is that it increases the incidence of ejaculation disorders. All of the alpha(1)-adrenoceptor antagonists have been shown to reduce symptom scores and increase peak urinary flow rates in BPH. The nonselective alpha(1)-adrenoceptor antagonists (prazosin, terazosin and doxazosin) were developed as antihypertensives, and hypotensive-related side effects are the main problem with these agents in BPH. These side effects can be diminished by reducing peak concentrations of the drugs, as with once-daily alfuzosin, or by using the uroselective antagonist tamsulosin. Phytopharmaceuticals are commonly used in the treatment of BPH, such as saw palmetto berry which has been shown to improve the symptoms and peak urinary flow rate. Androgen receptor antagonists are not used in BPH because of their adverse effects. Newer drugs under development for the treatment of BPH include alpha(1)-adrenoceptor antagonists that show more selectivity for alpha(1A)-adrenoceptors than tamsulosin, combined 5alpha-reductase/alpha(1)-adrenoceptor inhibitors and combined type 1/type 2 5alpha-reductase inhibitors. New targets for the drug treatment of BPH include indothelin, growth factors, estrogens and the phosphodiesterase isoenzymes.

eMelanoBase: An online locus-specific variant database for familial melanoma

A proportion of melanoma,prone individuals in both familial and non,familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1a, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A,p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model,view. controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.e, du.au:8080/melanoma.html.

Boletim eletr??nico de bibliografias especializadas: burocracia

A 1a edi????o do Boletim Eletr??nico de Bibliografias Especializadas traz publica????es com o tema Burocracia. As obras fazem parte do acervo da Biblioteca Graciliano Ramos, da Escola Nacional de Administra????o P??blica (ENAP). A literatura trata, por um lado, os aspectos da burocracia enquanto modelo de funcionamento do Estado. J?? em ou?? tra conota????o, explora caracter??sticas do corpo funcional do governo, suas peculiari?? dades e seu papel no processo de policy-making. O objetivo ?? divulgar publica????es que auxiliem gestores p??blicos e pesquisadores na reflex??o e compreens??o desse assunto, para al??m das propagadas "disfun????es" da burocracia (morosidade, falta de efici??ncia da m??quina p??blica, foco nos processos e n??o nos resultados).

A reforma do Estado no contexto latino-americano: coment??rios sobre alguns impasses e poss??veis desdobramentos

O artigo se constitui em uma reflex??o sobre a reforma do Estado nos pa??ses latinoamericanos, em especial no que se refere a seu aparato institucional ??? a "m??quina administrativa". Identificadas como reformas de 2a gera????o (as de 1a s??o as do reajuste macroecon??mico), o conjunto dos esfor??os modernizadores busca a regenera????o das institui????es p??blicas duramente afetadas pela crise econ??mico-financeira dos anos 80, e/ou at?? mesmo a cria????o de novas institui????es, visando a constru????o de um Estado forte, apoiado em uma economia din??mica e competitiva, da qual ?? parceiro e regulador, al??m de desempenhar de forma adequada suas fun????es cl??ssicas. O autor discute as quest??es institucionais e sociais (accountability, governance, conex??es entre as reformas econ??mico-financeiras), a mudan??a de paradigma do papel do Estado e os desafios a serem enfrentados.