RESUMEN
BACKGROUND: Several studies have shown an association between 25-hydroxyvitamin D (25[OH]D) levels and multiple sclerosis (MS) susceptibility and/or level of disease activity in patients treated with first line drugs. AIMS: To investigate whether baseline 25[OH]D values could influence disease activity also during treatment with the second-line drug fingolimod (FTY). PATIENTS AND METHODS: We enrolled 176 MS patients who started FTY at the San Raffaele Hospital (OSR) MS center with available 25[OH]D measurement at the time of treatment start. We then prospectively followed them for 2 years with periodic clinical examinations and MRI scans. RESULTS: We found no linear correlation between baseline 25[OH]D levels and annualized relapse rate (ARR) or time to first relapse. However, we observed that patients with serum 25[OH]D ≥ 100 nmol/l showed a lower number of Gd+ and combined unique activity (CUA) lesions at baseline compared to patients with the lowest 25[OH]D levels (less than 50 nmol/l, p value < 0.05). Moreover, they showed fewer CUA lesions at 2-year follow-up also when accounting for baseline level of disease activity (p value < 0.05). CONCLUSIONS: In patients treated with FTY, those with the highest baseline 25(OH)D levels had a significantly lower number of active lesions at baseline; the same effect, even if weaker, was observed also at 2-year follow-up when adjusting for baseline disease activity. Given Vitamin D supplementation safety profile, also if a causal effect has not yet been shown, most of MS patients could probably benefit from 25[OH]D levels above those currently considered to be sufficient.
Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Vitamina D/análogos & derivados , Adulto , Femenino , Gadolinio/efectos adversos , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Estadísticas no Paramétricas , Factores de Tiempo , Vitamina D/sangreRESUMEN
Bacillus subtilis BS5 is a soil isolate that produces promising yield of surfactin biosurfactant in mineral salts medium (MSM). It was found that cellular growth and surfactin production in MSM were greatly affected by the environmental fermentation conditions and the medium components (carbon and nitrogen sources and minerals). Optimum environmental conditions for high surfactin production on the shake flask level were found to be a slightly acidic initial pH (6.5-6.8), an incubation temperature of 30 degrees C, a 90% volumetric aeration percentage, and an inoculum size of 2% v/v. For media components, it was found that the optimum carbon source was molasses (160 ml/l), whereas the optimum nitrogen source was NaNO(3) (5 g/l) and the optimum trace elements were ZnSO(4).7H(2)O (0.16 g/l), FeCl(3).6H(2)O (0.27 g/l), and MnSO(4).H(2)O (0.017 g/l). A modified MSM (molasses MSM), combining the optimum medium components, was formulated and resulted in threefold increase in surfactin productivity that reached 1.12 g/l. No plasmid could be detected in the tested isolate, revealing that biosurfactant production by B. subtilis isolate BS5 is chromosomally mediated but not plasmid-mediated.
Asunto(s)
Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/metabolismo , Lipopéptidos/metabolismo , Péptidos Cíclicos/metabolismo , Tensoactivos/metabolismo , Aminoácidos/farmacología , Cationes/farmacología , Medios de Cultivo/farmacología , Glucosa/farmacología , Concentración de Iones de Hidrógeno , Lipopéptidos/química , Lipopéptidos/aislamiento & purificación , Maltosa/farmacología , Nitratos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Sorbitol/farmacología , Sacarosa/farmacología , Tensoactivos/química , Tensoactivos/aislamiento & purificación , TemperaturaRESUMEN
Several N-alkyl, aryl, and aralkyl-N'-2-biphenylthiourea derivatives have been synthesized and cyclodesulphurized into the corresponding 6-substituted aminophenanthridines. The ring closure was brought about with mercuric chloride, phosphoryl chloride or polyphosphoric acid. Phosphoryl chloride was found to be the most efficient in inducing ring closure and producing the highest yield of cyclized products. The results of study on the cyclodesulphurization reaction mechanism suggested the formation of a carbodiimide intermediate and identified some of the organic mercurials involved in the various stages of the reaction.