RESUMEN
BACKGROUND: Leprosy is complicated by immunological reactions which can occur before, during and after successful completion of multidrug therapy. Genetic studies have suggested that polymorphisms in toll-like receptors (TLRs) may affect the susceptibility of an individual with leprosy to developing Type 1 reactions. OBJECTIVES: To examine the gene and protein expression of TLRs in the cutaneous lesions of leprosy Type 1 reactions at the onset of reaction and during systemic corticosteroid therapy. METHODS: Patients who were being treated for leprosy type 1 reactions with corticosteroids as part of a randomized controlled trial of corticosteroid treatment had skin biopsies performed before, during and at the end of treatment. The gene and protein expression of TLR2 and TLR4 were measured. RESULTS: We have demonstrated that the gene hARP-P0 is a suitable control gene for TLR gene expression studies in this population. The gene and protein expression of TLR2 and TLR4 were both reduced significantly during corticosteroid treatment. CONCLUSIONS: This is the first study to examine the expression of TLR2 and TLR4 in vivo in individuals experiencing leprosy Type 1 reactions. The data support the possibility of an important role for TLR2 and TLR4 in the pathogenesis of this important complication of leprosy.
Asunto(s)
Glucocorticoides/uso terapéutico , Lepra/tratamiento farmacológico , Receptor Toll-Like 2/fisiología , Receptor Toll-Like 4/fisiología , Adolescente , Adulto , Análisis de Varianza , Antibióticos Antituberculosos/uso terapéutico , ADN Complementario/biosíntesis , Quimioterapia Combinada , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Lepra/genética , Lepra/mortalidad , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Prednisolona/uso terapéutico , Receptor Toll-Like 2/efectos de los fármacos , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/efectos de los fármacos , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: We conducted an ex-vivo analysis and a study in healthy subjects to compare magnesium bioavailability after administration of Sucrosomial® magnesium or commercially available preparations of magnesium citrate, magnesium oxide and magnesium bisglycinate. MATERIALS AND METHODS: In the ex-vivo study we simulated magnesium intestinal absorption after digestion through sections of intestinal mucosa isolated from rats. We compared the absorption of magnesium oxide and Sucrosomial® magnesium at two different concentrations: 32.9 mg/ml and 329 mg/ml. The human study was a single day double-blinded repeated crossover study in healthy subjects. Each subject was administered 350 mg magnesium in different formulations (Sucrosomial® magnesium, magnesium citrate, magnesium oxide or magnesium bisglycinate) after 1 week of washout. We collected blood and urine samples to measure magnesium concentration in blood, urine and red blood cells. RESULTS: The ex-vivo evaluation showed that magnesium absorption after administration of Sucrosomial® magnesium was faster and with higher rates compared to a standard formulation of magnesium oxide. This finding was further confirmed by the results of the study in healthy subjects, that showed a more evident increase in magnesium concentration after administration of Sucrosomial® magnesium compared to the other formulations. In particular, the increase in magnesium concentration from baseline to 24 h was statistically higher in blood and in urine for Sucrosomial® magnesium compared to magnesium oxide, while in red blood cells Sucrosomial® magnesium had a statistically significant advantage compared to magnesium bisglycinate. CONCLUSIONS: Our findings suggest that Sucrosomial® magnesium leads to an increased bioavailability of magnesium compared to other formulations. Further studies are needed to investigate if this advantage turns into more evident clinical efficacy.