Cronobiología del sistema inmune / Immune system chronobiology

La cronobiología es la disciplina que ha estudiado la organización temporal de los procesos que ocurren en los seres vivos, los mecanismos que las originan y sus alteraciones. En 1832, Agustín de Candolle demostró que bajo condiciones constantes el período de los ciclos de movimientos de las plantas duraba unas 24 horas, con lo que añadió una evidencia de la naturaleza endógena de los ritmos biológicos. En los mamíferos, se ha estimado que aproximadamente el 10 por ciento del genoma está bajo un control circadiano. Desde la década de los años 70´s se observó que la respuesta inmune dependía de la hora del día en la cual se analizaba y que la susceptibilidad a las infecciones dependía también de la hora en la cual el organismo fuera infectado. Recientemente se ha establecido una relación entre el ciclo circadiano y la respuesta inmune. Este trabajo trata las ventajas del conocimiento del ritmo circadiana de los mecanismos inmunitarios y la importancia del uso de la cronoterapia sobre los osciladores de las células del sistema inmune en los trastornos inmunitarios, lo cual pudiera evitar complicaciones en los pacientes(AU)

Chronobiology is the science that studies temporary organization of the processes that happen in organisms, the mechanisms that originate them and its disorders. Austin of Candolle demonstrated that under constant conditions the period of the cycles of the plants' movements it lasted some 24 hour, adding an evidence of the endogenous nature of the biological rhythms in 1832. In mammals, has been considered approximately 10 percent of genome under circadian control. Since decade of 70´s, was observed that immune response depends of day´s hours in which it was analyzed, and the susceptibility to infections also depends of the hour in which an organism is infected. It has begun to establish relationship between circadian cycle and immune response recently. This work intends to give us the advantages of the knowledge of circadian rhythms of immune mechanisms and the importance of the chronotherapy´s use on the oscillators of the immune system´s cells in immunity dysfunctions and it would avoid complications in the patients(AU)

Formulation and evaluation of mini-tablets-filled-pulsincap delivery of lornoxicam in the chronotherapeutic treatment of rheumatoid arthritis

In this present research work, we have designed a pulsincap formulation comprising mini-tablets, which to the best of our knowledge this combination has not been reported yet. We successfully combined the advantages of minitablets technology to meet the optimized requirements of our pulsincap formulation. Our main aim was to target lornoxicam to treat rheumatoid arthritis as per the chronotherapeutic pattern of the disease. Directly compressing method was used to prepare mini-tablets. The drug, polymers and combine mixtures of drug and polymers was evaluated for preformulation testing. Prepared mini-tablets were also evaluated for physicochemical, dissolution and stability studies. From FTIR and DSC evaluation, we found no interaction between the drug and polymers used. For mini-tablets, all the physico-chemical parameters were in limit. The mini-tablets of lornoxicam were filled into an insoluble body of capsule, and its opening was sealed by plugging it with a polymer. The complete capsule body after sealing with a cap was given enteric coating. Different polymers in various concentrations were used as a plug, to identify the most suitable which gives a complete lag time of 5 hours when combined with 5% CAP coating. HPMC-K100M in 30% and sodium alginate in 40% concentrations were identified as the most suitable plugs. Our optimized pulsincap formulations releases lornoxicam after a lag time of 5 hrs and maximum portion of the drug will be released in the early morning hours. It was also found to be stable for a period of 6 months as per ICH guidelines

Chronobiological and chronopharmacological studies of ketoprofen and its solid dispersion form using adjuvant arthritis model in rats.

Chronobiology of rheumatoid arthritis (RA) was studied using a standard adjuvant arthritis animal model. Chronopharmacology of ketoprofen, and its solid dispersion forms was also studied. Temporal variations in the degree of articular inflammation (paw volume) and progression of articular destruction were studied by injecting Freund's Complete Adjuvant (FCA) at 0800 and 2000 hrs. Temporal variations in anti-inflammatory effects and ulcerogenic effect were also studied by administration of plain ketoprofen (20 mg/kg) and its solid dispersion with hydroxypropyl beta-cyclodextrin (equivalent to 20 mg/kg of ketoprofen) at the same time points (0800 and 2000 hrs) twice weekly for 22 days. Solid dispersion of ketoprofen was found to be more effective in inhibiting progression of RA. The incidence and severity of ulcers was found to be less with the solid dispersion. The protective effect of ketoprofen and its solid dispersion was significantly higher when these were administered at 0800 hrs. The incidence of ulceration was more in 2000 hrs group. Thus, it was observed that in the adjuvant induced arthritis model, inflammation and articular damage was significantly greater in the rest period of diurnally active rats than in the activity phase. KPF and its solid dispersion showed better protection from inflammation in the morning than in the evening.