Resistance to chemotherapy in cancer cells is mainly mediated by overexpression of P-glycoprotein (Pgp), a plasma membrane ATP-binding cassette (ABC) transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. Pgp consists of two homologous halves each containing a transmembrane domain and a cytosolic nucleotide-binding domain (NBD) which contains two consensus Walker motifs, A and B, involved in ATP binding and hydrolysis. The protein also contains an S signature characteristic of ABC transporters. The molecular mechanism of Pgp-mediated drug transport is not known. Since the transporter has an extraordinarily broad substrate specificity, its cellular function has been described as a "hydrophobic vacuum cleaner". The limited knowledge about the mechanism of Pgp, partly due to the lack of a high-resolution structure, is well reflected in the failure to efficiently inhibit its activity in cancer cells and thus to reverse multidrug resistance (MDR). In contrast to the difficulties encountered when studying the full-length Pgp, the recombinant NBDs can be obtained in large amounts as soluble proteins. The biochemical and biophysical characterization of recombinant NBDs is shown here to provide a suitable alternative route to establish structure-function relationships. NBDs were shown to bind ATP and analogues as well as potent modulators of MDR, such as hydrophobic steroids, at a region close to the ATP site. Interestingly, flavonoids also bind to NBDs with high affinity. Their binding site partly overlaps both the ATP-binding site and the steroid-interacting region. Therefore flavonoids constitute a new promising class of bifunctional modulators of Pgp.

A necessidade de maior número de dados sobre prevalência das hepatites por vírus em nosso meio levou-nos a estudar a freqüência das hepatites por vírus na Unidade de Fígado de São Paulo. Foram estudados 154 pacientes atendidos consecutivamente de novembro de 1980 a novembro de 1984. O emprego de marcadores para hepatite A (anti-VHA-IgM), hepatite B (AgHB8, anti-HB6 e anti-HB8) e a ausência dos mesmos para hepatite não-A, não-B (NANB), permitiu verificar a freqüência das mesmas que foi, respectivamente, de 52,6%, 27,3% e 20,1%. A hepatite A caracterizou-se pela maior freqüência em jovens, contacto prévio com doente ou ingestão de alimento suspeito. Na hepatite B os dados epidemiológicos preponderantes foram transmissão parenteral não-transfusional, contacto prévio e alta incidência em profissionais de saúde. Na hepatite NANB predominaram os casos pós-transfusionais (34,5%). Ausência de antecedentes epidemiológicos foi observada em 30-40% dos pacientes dos três grupos.

As few reports on the prevalence of each type of viral hepatitis have been published in our country, we studied 154 patients with acute viral hepatitis consecutively seen at the Liver Unit from November 1980 to November 1984. The frequency of hepatitis A, B and non-A, non-B was 52.6%, 27.3% and 20.1% respectively. Greater frequency in young people, previous contact with infected patients and ingestion of suspected foods were the predominant epidemiological features in the hepatitis A group. Hepatitis B was characterized by the parenteral, non-transfusional exposure, previous contact and a high occurence in health-care workers. A history of blood transfusion was a significant finding in the hepatitis non-A, non-B group. Finally, the routes of transmission were unknown in 30-40% of the three groups of patients.