RESUMEN
Pancreatic rat islets are encapsulated by a siliceous layer deposited on the surface of single islets upon reaction with gaseous siliceous precursors. The process preserves original islet dimensions and does not suppress viability or function. The encapsulated material is homogeneously distributed on the islet surface, and layer thickness can be controlled in the 0.1-2.0 microm interval. Dynamic perfusion experiments with glucose stimulation were carried out in both encapsulated and non-encapsulated islets. Results were treated according to a kinetic model presented here for the analysis of perfusion data; the model tested by literature data, was used to substantiate the diffusion features of the siliceous layer, which does not affect mass transfer of insulin but which modifies the texture of the islet surface tissue. The clinical potential of silica encapsulation was demonstrated by in vivo experiments using encapsulated islets transplanted into diabetic rats. Transplantation was carried out in both inbred and outbred rats and indicated prolonged restoration of normal glycaemia levels and protection from immunological attack.
Asunto(s)
Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos/instrumentación , Islotes Pancreáticos/metabolismo , Membranas Artificiales , Dióxido de Silicio , Animales , Materiales Biocompatibles , Supervivencia Celular , Simulación por Computador , Técnicas de Cultivo , Diabetes Mellitus Experimental/metabolismo , Geles , Glucosa/farmacología , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/citología , Trasplante de Islotes Pancreáticos/métodos , Microesferas , Modelos Biológicos , Ratas , Ratas Endogámicas Lew , Ratas Sprague-DawleyRESUMEN
BBR 2160 ((+-)3-ethyl,5-methyl,2-([2-(formylamino)-ethyl]- thiomethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxy late, CAS 118587-22-7) is a new calcium entry blocker (CEB) which completely displaces 3H-nitrendipine from binding sites, is 10 times more potent than amlodipine (A) and equiactive with nifedipine (N). On the rat aorta contracted by 10 mmol/l Ca++, or 45 mmol/l K+, BBR 2160 shows higher CEB activity than N and A, achieving the maximum effect on voltage operated channels-induced contractions in 6 h, while N takes about 2 h. BBR 2160, N and A negatively affect the chronotropism on spontaneously beating, and inotropism on electrically driven guinea pig atria, respectively. In vitro BBR 2160 has marked vasoselectivity. Administered orally to conscious hypertensive rats (SHR) and renal hypertensive dogs (RHD), it caused a dose-dependent reduction in systolic blood pressure with a relatively slow onset, peak effect at 3-6 h and duration over 6 h. BBR 2160 and A have more pronounced activity on SHR than on normotensive rats (NR) (ED20 NR/SHR 3.3 for both compounds), while the antihypertensive and hypotensive activities of N are in the same dose-range (ED20 NR/SHR 1.3). No tolerance develops to the antihypertensive effects of BBR 2160 after five days' dosing up to 3.2 mg/kg in SHR and 1 mg/kg in RHD. In instrumented conscious normotensive dogs BBR 2160, N and A mostly lower diastolic blood pressure and total peripheral resistance, and do not increase total oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)