Effect of viscosity upon hydrodynamically controlled natural aggregates of animal cells grown in stirred vessels.

The effect of medium viscosity upon cell growth and aggregate characteristics of baby hamster kidney (BHK) cells cultivated in stirred tanks was evaluated. Two thickening agents were tested, 9300 MW dextran and a low-viscosity sodium (carboxymethyl)-cellulose; both were used in two different sets of experiments: (i) 250 cm3 Wheaton spinner flasks with a ball impeller operated at 45 rpm; (ii) 500 cm3 Corning spinner flasks with a paddle impeller, operated at constant power dissipation (88 cm2 s-3). Aggregate diameter and the fraction of cells in aggregates increased with the increase in viscosity. Power laws were applied to the experimental results. A dependence of aggregate size upon power dissipation of the order of -0.19 and kinematic viscosity of 0.34 and 0.49 for the constant agitation and constant power dissipation tests were obtained, respectively. A model based upon the entire universal-equilibrium range (i.e., the entire spectrum of isotropic eddies) was used to predict theoretical relationships between the variables studied. The model leads to a power dependence of -0.25 for the energy dissipated in the entire universal-equilibrium range and between 0.25 and 0.5 for the kinematic viscosity in the viscous dissipation subrange, depending on the energy correlation used; it also gives a good explanation for the dependence of aggregate size on the hydrodynamics of the vessel.

Repeated-batch cultures of baby hamster kidney cell aggregates in stirred vessels.

Natural aggregates of Baby Hamster Kidney cells were grown in stirred vessels operated as repeated-batch cultures during more than 600 hours. Different protocols were applied to passaging different fractions of the initial culture: single cells, large size distributed aggregates and large aggregates. When single cells or aggregates with the same size distribution found in culture are used as inoculum, it is possible to maintain semi-continuous cultures during more than 600 hours while keeping cell growth and viability. These results suggest that aggregate culture in large scale might be feasible, since a small scale culture can easily be used as inoculum for larger vessels without noticeable modification of the aggregate characteristics. However, when only the large aggregates are used as inoculum, it was shown that much lower cell concentrations are obtained, cell viability in aggregates dropping to less than 60%. Under this 'selection' procedure, aggregates maintain a constant size, larger than under batch experiments, up to approximately 400 hours; after this time, aggregate size increases to almost twice the size expected from batch cultures.

Prazosin na hipertensão arterial essencial moderada e severa, não controlada com clortalidona. Estudo multicentrico / Prazosin in moderate or severe essential arterial hypertension, non-controlled with chlorthalidone. A multicentric study

Estudo multicentrico abrangendo 19 centros de cardiologia e incluindo 398 casos de hipertensao essenciais (hipertensao moderada ou grave), foi desenvolvido em tres etapas (fases I, II e III). Na 1a. utilizou-se a clortalidona; na 2a., clortalidona 50 mg + prazosin em doses crescentes ate 15 mg/24h e, na 3a., clortalidona 50 mg +prazosin 15mg + propranolol em doses progressivas ate 240mg/24h, enquanto nao se obtivesse a normalizacao tensional. 306 pacientes foram tratados na fase II e,destes 76,5% normalizaram a PA. Quarenta hipertensos cumpriram a fase III, obtendo-se normalizacao tensional em 60% dos mesmos.A frequencia cardiaca nao apresentou variacoes significativas nas fases I e II, nao ocorrendo o mesmo na fase III. Ocorreram reacoes adversas na fase I, responsaveis por 5 casos de exclusao; na fase II foram excluidas 24 pacientes, 14 por "tontura" que constituiu a manifestacao adversa mais importante. Nesta fase, predominaram reacoes de leve intensidade e sua ocorrencia verificou-se na primeira e segunda semanas de prazosin. Controles laboratoriais revelaram variacoes discretas da potassemia, uremia, creatinemia e uricemia nas fases I e II proprias do emprego da clortalidona. Nao houve modificacao significativa da colesterolemia e trigliceridemia em nenhumas das fases