RESUMO
Metabolic syndrome, a cluster of risk factors that increase the risk of cardiovascular morbidity and mortality, is common in patients with hypertension. Chronic renin-angiotensin-aldosterone system (RAAS) activation, shown by elevated plasma renin activity (PRA), is implicated in many of the features of metabolic syndrome. The direct renin inhibitor aliskiren may be of benefit in this patient group as aliskiren targets the RAAS at the rate-limiting step. In this double-blind study, 141 patients with hypertension (mean baseline BP 155/93 mm Hg) and metabolic syndrome (modified National Cholesterol Education Program ATP III criteria) were randomized to aliskiren 300 mg or irbesartan 300 mg once daily. Patients treated with aliskiren 300 mg had their mean sitting blood pressure (BP) lowered by 13.8/7.1 mm Hg after 12 weeks, significantly greater (P≤0.001) than the 5.8/2.8 mm Hg reduction observed in patients treated with irbesartan 300 mg. A significantly greater proportion of patients treated with aliskiren achieved BP control to <135/85 mm Hg (29.2 vs 16.7% with irbesartan; P=0.019). Aliskiren treatment led to a 60% decrease in PRA from baseline, whereas irbesartan increased PRA by 99% (both P<0.001). Aliskiren and irbesartan had similar effects on glucose and lipid profiles and on a panel of biomarkers of inflammation and cardiovascular risk. Both aliskiren and irbesartan were well tolerated. Collectively, these results suggest that aliskiren 300 mg may offer treatment benefits compared with irbesartan 300 mg for BP reduction in patients with hypertension and metabolic syndrome.
Assuntos
Amidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Fumaratos/uso terapêutico , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Tetrazóis/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Irbesartana , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Resultado do TratamentoRESUMO
A large-scale immunoaffinity (IA) purification process was developed for the isolation of recombinant soluble antigen CD4 (sCD4) from Escherichia coli fermentations. The monoclonal antibody used for IA purification of sCD4 recognized a conformation-dependent epitope on the surface of domain 1 of CD4. IA chromatography was used to purify both sCD4-183, consisting of the N-terminal 183 amino acids of human CD4, and sCD4-PE40, a fusion protein consisting of the N-terminal 178 amino acids of CD4 and amino acids 1-3 and 253-613 of Pseudomonas exotoxin A (PE40). sCD4-183 was purified from E. coli cell pellets using cell disruption, protein solubilization, oxidation, Q-Sepharose anion-exchange and IA chromatography steps. sCD4-PE40 was purified from cell pellets using cell disruption, protein solubilization, oxidation, Cu(2+)-immobilized metal-affinity chromatography, anion-exchange and IA chromatography steps. The IA-purified sCD4 analogues demonstrated the correct apparent molecular masses on SDS/PAGE. The immobilized monoclonal antibody appeared to select for correctly folded CD4 protein, since sCD4-183 and sCD4-PE40 purified by the IA method bound human-immunodeficiency-virus glycoprotein gp120 (HIV gp120) in vitro. sCD4-PE40 purified by IA chromatography also inhibited protein synthesis in CV-1 cells expressing HIV gp120/160 at the cell surface. Relatively high recoveries of sCD4-183 and sCD4-PE40 were observed in the IA step of the purification process (71 and 79% recovery respectively). The results demonstrate that immobilized monoclonal antibodies directed against conformational epitopes may be used for rapid purification of gram amounts of correctly folded protein from mixtures of oxidized E. coli proteins.
Assuntos
Antígenos CD4/isolamento & purificação , Escherichia coli/metabolismo , Anticorpos Monoclonais , Cromatografia de Afinidade , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Humanos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes/isolamento & purificação , Análise de RegressãoRESUMO
Paulomycin A, C34H46N2O17S and paulomycin B, C33H44N2O17S are two antibiotics produced by Streptomyces paulus strain 273 (UC 5142). Both antibiotics, which are mainly active against a variety of Gram-positive bacteria, contain an isothiocyanate group and in this respect they are related to senfolomycins A and B and proceomycin.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Dissacarídeos , Espectroscopia de Ressonância Magnética , Espectrofotometria Ultravioleta , Streptomyces/metabolismoRESUMO
Improved fermentation and isolation procedures for antitumor antimetabolites U-42,126 and U-43,795 increased drug yields 30-fold. The sensitivity limit of a newly developed assay is 0.03 mug of U-42,126 and 2.0 mug of U-43,795 per ml. The in vitro antimicrobial effect of both drugs was antagonized by histidine.
