Potential therapeutic role of melatonin in hepatobiliary diseases: current evidence and clinical observations.

Melatonin (MEL) is produced and secreted by the pineal gland as well as the small intestine, liver, retina, lymphocytes, and melanocytes in the skin in both experimental animals as well as in humans. While pineal and retinas MEL is closely related to the light/dark cycle, the production of MEL by other so called extrapineal tissues is independent of such circadian rhythm. Among the primary mechanisms of action of MEL in humans, the most important are interaction of MEL with specific receptors (M1, M2, M3) and the MEL 'scavenging' activity against the formation of free oxygen metabolites as a result of MEL's ability to transfer free electrons and stimulation of the expression of redox reaction enzymes. In addition, MEL binds to intracellular proteins such as calmodulin, thereby affecting the course of cell cycle, and it has been shown to activate of nuclear receptors belonging to the retinoid orphan receptors/retinoid Z receptors (ROR/RZR) subfamily. MEL exerts regulatory effects on the master clock regulating diurnal rhythms. This updated review presents current view on the synthesis and metabolism of MEL and the growing body of experimental evidence transferable to the practical medicine supporting a pleiotropic molecule beneficial effects on the health including protection against various organ abnormalities, including internal organs such as the liver. Although the beneficial effects of MEL in various types of liver damage have been well documented in experimental studies, there are relatively few studies on liver dysfunction in humans. Considering the worldwide obesity pandemic often associated with the occurrence of steatohepatitis and cirrhosis, the beneficial effects of MEL in liver pathology should be proven in randomized trials involving patients presenting with hepatic disorders.

Considerations on juvenile chronic arthritis with generalized (polysystemic) onset.

A trial is presented of evaluation of the frequency of clinical symptoms and signs, activity of disease process, and course of the disease in a group of children with juvenile chronic arthritis with generalized manifestations at onset. The analysed group comprised 36 children aged from 2 to 15 years. The duration of the disease was from 6 months to 13 years. The evaluation of the most frequent symptoms and signs in the so called early period of the disease covered the first year after the beginning of the first clinical signs. During the disease involvement of many internal organs develops and establishing of correct diagnosis at the onset is difficult, particularly, since in this initial period the signs of articular involvement may be absent or slight. Arthritis in this early period was observed in only 7 of 36 children. The most frequent symptoms and signs in decreasing frequency were: fever, rash, arthralgias, lymphadenopathy, hepatosplenomegaly. Heart involvement was noted in 16 of 36 cases, and pneumonia in 7 of 36. Anaemia and leucocytosis were present in all cases. Amyloidosis was recognized in 6 of 36 cases. In view of the severe course of the disease all children were treated with glycocorticoids, and cytostatic agents were given to those with evidence of amyloidosis.