Conscious and anesthetized non-human primate safety pharmacology models: hemodynamic sensitivity comparison.

INTRODUCTION: Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models. METHODS: Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and dopamine (0.05 mg/kg/min, 30 min infusion) were given intravenously to all models. RESULTS: Remifentanil decreased heart rate (HR), systolic, mean and diastolic systemic arterial pressures (SAP) in anesthetized animals while conscious monkeys presented an increase in HR, systolic, mean and diastolic SAP, as seen in humans for the respective state of consciousness (conscious and anesthetized). Esmolol decreased HR, systolic, mean and diastolic SAP in anesthetized monkeys while only HR, systolic and mean SAP achieved a statistically significant decrease in the conscious model. The amplitude of SAP reduction was greater in anesthetized models, while the amplitude of HR reduction was greater in the conscious and anesthetized cynomolgus models than in the anesthetized rhesus model. Dopamine induced a significant increase in HR, systolic, mean and diastolic SAP in anesthetized models without any statistically significant effect on HR and SAP in the conscious model. DISCUSSION: The amplitude of hemodynamic and chronotropic alterations induced by positive control drugs was generally greater in anesthetized than in conscious models and statistical significance was achieved more often with the anesthetized models. These results suggest that an anesthetized model may be valuable as part of a drug screening program for cardiovascular safety evaluations in addition to a conscious model.

Microesferas biodegradables de poli(D, L-láctico) conteniendo progesterona / Biodegradable microspheres of poly(D, L-lactide) containing progesterone

Se obtuvieron microesferas de poli(D,L-láctico) conteniendo progesterona por medio de una emulsión simple aceite en agua empleando una técnica de evaporación de solvente. Se realizó un experimento con un diseño factorial 23 para estudiar el efecto de tres variables independientes (cantidad de principio activo, cantidad de polímero y concentración de alcohol polivinílico) sobre las variables dependientes (encapsulación de principio activo y tamaño de partícula). Las tres variables independientes influyeron significativamente sobre la encapsulación de progesterona. En el caso del tamaño de partícula, las variables que ejercieron una influencia significativa fueron la concentración de alcohol polivinílico y la cantidad de polímero. Los estudios de liberación in vitro han mostrado que de acuerdo al tamaño de partícula se pueden obtener formulaciones que logran liberar progesterona en pocos días u obtener una liberación sostenida durante 28 días. El estado físico del fármaco se investigó por calorimetría diferencial de barrido. Los estudios muestran que existe una interacción fisicoquímica entre la progesterona y el polímero

Microspheres of poly(D,L-lactide) containing progesterone were prepared by the solvent evaporation method using a simple oil water emulsion. 23 factorial design was used to determine the effect of three independent variables (amount of drug, amount of polymer and concentration of polyvinyl alcohol) over the dependent variables (drug content and particle size). The three independent variables influenced significantly over the percentage drug encapsulated. On the other hand, in the particle size case, the variables which produced a significantly influence were the polyvinyl alcohol concentration and the amount of polymer. The in vitro release studies have shown that according to the particle size, it can be obtained formulations which are able to release progesterone in a few days or a sustained release among 28 days. The physical state of drug has been examined by differential scanning calorimetric. The studies indicate that exists a physicochemical interaction between the progesterone and the polymer

[Rheumatic features of Grave's disease in children]. / Aspectos reumáticos de la enfermedad de Graves en niños.

We report three cases from girls with Graves disease who developed serious rheumatic manifestations. One patient had systemic lupus erythematosus with articular, renal, neurological and cardiac afectation with fatal outcome. Other patient presented clinical features of scleroderma with skin thickness, myopathy, arthritis, Raynaud's phenomenon and findings of pulmonary fibrosis. A lupus-like syndrome associated to methimazole therapy (polyarthritis, rash and hemolytic anemia) with positive Cel-LE preparations but negative antinuclear-antibodies was observed in a third patient. A careful history and the recognition of these manifestations will help in the identification of these syndromes.

Cryptosporidium sp in 300 children with and without diarrhea.

Cryptosporidium sp was searched prospectively by means of the Ziehl-Nielsen acid fast staining of stools in 403 samples obtained from patients with diarrhea (n =/152) or other non-gastrointestinal diseases (n =/152) in a six month period. Cryptosporidium was present in 11/304 samples (3.6%), 9 (81%) were taken from patients with diarrhea. Oocysts were detected in 5% of stools form malnourished (II or III) children with diarrhea; 10/11 (91%) with positive-cryptosporidium stools occurred in children less than one year of age. Cryptosporidium was present with increased frequency in malnourished children with diarrhea (p < 0.05).

Study of rheumatic manifestations and serologic abnormalities in patients with lepromatous leprosy.

We investigated the rheumatic and laboratory features associated with rheumatic syndromes in 32 patients with lepromatous leprosy. Twenty-seven (84%) developed a broad range of rheumatic manifestations, the most common being the presence of arthritis which was symmetric and polyarticular, resembling rheumatoid arthritis. The laboratory abnormalities included an elevated sedimentation rate in 32 cases (100%), a positive rheumatoid factor in 6 (18.7%), and antinuclear antibodies in one (3.1%). A careful history and the recognition of rheumatic manifestations will help in the identification of this type of leprosy.