RESUMEN
In this study, we aimed to determine the drug-drug interaction potential between atorvastatin (ATOR), and talinolol (TAL). Concentration-dependent effects of ATOR on the intestinal permeability of TAL were investigated by an in situ intestinal perfusion method. Dose-dependent effects of ATOR on TAL exposure were evaluated by measuring plasma concentrations after oral administration in rats. ATOR slightly changed the intestinal secretion of TAL in jejunum but not in colon. Plasma AUC levels of TAL were elevated by co-administration of ATOR at low and high doses whereas medium doses of ATOR resulted in a decrease in TAL bioavailability. However, these changes were not statistically significant. In our study, the pharmacokinetics of TAL were not affected by the concurrent use of ATOR in rats. In conclusion, it should be considered that complex interplay between the efflux and uptake transporters in the tissues and inhibition of these transporters by modulating agents may overshadow individual effects of each other.
Asunto(s)
Antagonistas Adrenérgicos beta/metabolismo , Antagonistas Adrenérgicos beta/farmacocinética , Atorvastatina/farmacología , Absorción Intestinal/efectos de los fármacos , Propanolaminas/metabolismo , Propanolaminas/farmacocinética , Antagonistas Adrenérgicos beta/sangre , Animales , Disponibilidad Biológica , Interacciones Farmacológicas , Masculino , Propanolaminas/sangre , Ratas , Ratas WistarRESUMEN
Eighteen different sequence changes, including three novel alterations, were detected in GJB2, encoding connexin 26, in 371 Turkish probands with non-syndromic sensorineural hearing loss. Two frequently detected mutations, 35delG and delE120, were shown to have single origins based on the conserved genotypes of two closely linked microsatellite and five single nucleotide polymorphism markers. Carrier frequencies of 35delG and delE120 in Egypt and Turkic populations of the Near East provide insights about the origin of these two mutations.
Asunto(s)
Conexinas/genética , Mutación del Sistema de Lectura , Pérdida Auditiva Sensorineural/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Preescolar , Conexina 26 , Salud de la Familia , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Linaje , Topografía Médica , TurquíaRESUMEN
The aim of this study was to formulate biodegradable microspheres containing an anti-parkinsonian agent, bromocryptine mesylate, for brain delivery. The effect of formulation parameters (e.g. polymer, emulsifying agent type and concentration) on the characteristics of the microspheres produced, the efficiency of drug encapsulation, the particle size distribution and in vitro drug release rates from the bromocryptine mesylate microspheres were investigated using a 3(2) factorial design. Bromocryptine mesylate was encapsulated into biodegradable polymers using the following three different polymers; poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide). The SEM photomicrographs showed that the morphology of the microspheres greatly depended on the polymer and emulsifying agent. The results indicate that, regardless of the polymer type, increase in emulsifying agent concentration from 0.25-0.75% w/v markedly decreases the particle size of the microspheres. Determination of particle size revealed that the use of 0.75% w/v of emulsifying agent concentration and a polymer solution concentration of 10% w/v resulted in optimum particle size. In order to prepare biodegradable microspheres with high drug content and small particle size, selection of polymer concentration as well as emulsifying agent concentration is critical. Polymer type has a less pronounced effect on the percentage encapsulation efficiency and particle size of microspheres than on the t(50%). The microspheres prepared by all three polymers, at a polymer concentration of 10% w/v and an emulsifying agent concentration of 0.75% w/v with NaCMC:SO (4:1, w/v) mixture was as the optimum formulation.
Asunto(s)
Bromocriptina/administración & dosificación , Composición de Medicamentos/métodos , Biodegradación Ambiental , Encéfalo/metabolismo , Bromocriptina/farmacocinética , Sistemas de Liberación de Medicamentos , Excipientes , Humanos , Técnicas In Vitro , Ácido Láctico , Microscopía Electrónica de Rastreo , Microesferas , Tamaño de la Partícula , Poliésteres , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , SolventesRESUMEN
Cell proliferation and apoptosis in canine cutaneous histiocytomas and transmissible venereal tumours were examined in twenty cases. The Ki-67 immunohistochemistry and Tunel methods were used to detect mitotic activity and apoptosis, respectively. The number of Ki-67 immunoreactive cells was 11.65 (+/- 1.1706) in canine cutaneous histiocytomas and 17 (+/- 2.1751) in transmissible venereal tumours. The mean values of apoptotic cells for canine cutaneous histiocytomas and transmissible venereal tumours were 13.25 (+/- 1.8758) and 8.52 (+/- 1.1007), respectively. It was considered that mitotic activity and apoptotic indices were useful in differentiation of canine cutaneous histiocytomas and transmissible venereal tumours. The correlation values for canine cutaneous histiocytomas and transmissible venereal tumours were 0.359 (+/- 0.330) and -0.232 (+/- 0.344), respectively. No significant (P > 0.05) correlation was found between mitosis and apoptosis in these two tumour types.
Asunto(s)
Apoptosis , Enfermedades de los Perros/patología , Histiocitoma Fibroso Benigno/veterinaria , Mitosis , Neoplasias Cutáneas/veterinaria , Tumores Venéreos Veterinarios/patología , Animales , Diagnóstico Diferencial , Perros , Histiocitoma Fibroso Benigno/patología , Etiquetado Corte-Fin in Situ/veterinaria , Antígeno Ki-67 , Neoplasias Cutáneas/patologíaRESUMEN
We studied the levels of serum total carotenoids and uric acid in newly diagnosed cancer cases. The levels of carotenoids and uric acid in serum samples from 94 subjects with cancer affecting different sites (21 breast, 26 head and neck, 13 lung, 17 genitourinary and 17 other sites) were compared with those of 92 controls who were matched for age, sex, Quetelet index and smoking history. Mean (+/- SE) levels of carotenoids were significantly lower among the cases than the controls (51.41 +/- 3.32 vs. 102.75 +/- 4.52 micrograms/dl, P < 0.001), when all the different sites were considered together. The mean (+/- SE) uric acid levels among cases and controls were 5.14 +/- 0.16 mg/dl and 4.21 +/- 0.18 mg/dl (P < 0.001), respectively. It was of interest that patients with genitourinary cancer had the lowest serum carotenoids levels, and the highest levels were found in patients with breast cancer. These results are informative but do not establish a causal link. There was no apparent association between serum urate levels and cancer site. The data presented here do not provide support for the protective antioxidant properties of uric acid in cancer.