Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications.

Background Rheumatoid Arthritis (RA) patients show a higher risk of heart failure. The present study investigated possible causes of cardiac dysfunction related to thyroid hormone (TH) signaling in a RA mouse model. Methods A TNF-driven mouse model of RA[TghuTNF (Tg197)] was used. Cardiac function was evaluated by echocardiography. SERCA2a and phospholamban protein levels in left ventricle (LV) tissue, thyroid hormone levels in serum, TH receptors in LV and TH-related kinase signaling pathways were measured. T3 hormone was administered in female Tg197 mice. Results We show LV and atrial dilatation with systolic dysfunction in Tg197 animals, accompanied by downregulated SERCA2a. We suggest an interaction of pro-inflammatory and thyroid hormone signaling indicated by increased p38 MAPK and downregulation of TRß1 receptor in Tg197 hearts. Interestingly, female Tg197 mice showed a worse cardiac phenotype related to reduced T3 levels and Akt activation. T3 supplementation increased Akt activation, restored SERCA2a expression and improved cardiac function in female Tg197 mice. Conclusions TNF overexpression of Tg197 mice results in cardiac dysfunction via p38 MAPK activation and downregulation of TRß1. Gender-specific reduction in T3 levels could cause the worse cardiac phenotype observed in female mice, while T3 administration improves cardiac function and calcium handling via modified Akt activation.

Theophrastus Bombastus Von Hohenheim: Theological Reformer, Philosopher and Physician.

Theophrastus Bombastus Von Hohenheim (1493-1541), known as Paracelsus, was a German-Swiss Renaissance man. His interests included alchemy and medicine. During the early 1500s, he worked as a physician, introducing mineral-based therapies to treat ailments. He is credited with developing the first recipe for laudanum, a powerful opium-based pain medication. He had radical beliefs, claiming that supreme knowledge could be reached by observing nature, not by reading books. He expressed rebellious opinions on religious topics and, though devoted Christian, criticized the Catholic Church, preaching that the spirit of Christianity dwells in the human soul and not within the church walls. Paracelsus' efforts to "renovate" the expression of the Christian faith by limiting the ritual and augmenting the spirituality among believers are presented.

Pearls of Neonatal Intertrigo in Ancient Greek and Byzantine Medicine.

OBJECTIVE: Confirmation of knowledge of neonatal intertrigo in ancient Greek and Byzantine medicine. METHOD: A search of Thesaurus Linguae Graecae was conducted with the following terms as key words, "syggama", "xyggauma", "paratrimma" and "ektrimma". RESULTS: Ancient Greek medico-philosophers introduced therapeutic measures based upon herbs and minerals, while a similar therapeutic approach was also used by the Byzantines. Hippocrates of Kos (460-377) was among the first to introduce written instructions, also proposing preventive treatment with palliative and aromatic herbs. Cataplasms, thalassotherapy, and fumigation were used, combined with hygienic measures in the affected area. Chalk powder was also prescribed to absorb moisture. CONCLUSION: The main principles in the treatment of intertrigo remain the same, celebrating the ancient Greeks' methodology and rationalism.

Effects of hyper- and hypothyroidism on acetylcholinesterase, (Na(+), K (+))- and Mg ( 2+ )-ATPase activities of adult rat hypothalamus and cerebellum.

UNLABELLED: Thyroid hormones (THs) are recognized as key metabolic hormones, and the metabolic rate increases in hyperthyroidism, while it decreases in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na(+), K(+))- and Mg(2+)-ATPase in the hypothalamus and the cerebellum of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. Neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE (-23%, p < 0.001) and the Na(+), K(+)-ATPase activities (-26%, p < 0.001). Moreover, hypothyroidism had a similar effect on the examined enzyme activities: AChE (-17%, p < 0.001) and Na(+), K(+)-ATPase (-27%, p < 0.001). Mg(2+)-ATPase activity was found unaltered in both the hyper- and the hypothyroid brain regions. IN CONCLUSION: neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE and the Na(+), K(+)-ATPase activities. The decreased (by the THs) Na(+), K(+)-ATPase activities may increase the synaptic acetylcholine release, and thus, could result in a decrease in the cerebellar AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems.

In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by L-cysteine.

This study was undertaken in order to investigate a) the short- and long-term in vivo effects of cadmium (Cd) on brain acetylcholinesterase (AChE), (Na+, K+)-ATPase activities in adult rats, b) the concentration-dependent in vitro and in vivo (acute experiment) effects of Cd on the activity of those enzymes, c) the in vivo and in vitro effects of the antioxidant L-cysteine (Cys) on the above enzyme activities, and d) the evaluation of brain total antioxidant status after in vivo Cd, L-cysteine, or L-cysteine+Cd administration in rats. In vitro, CdSO4 inhibited pure and brain AChE in concentrations higher than 0.1 mM, while it activated by approximately 70% (P<0.001) brain Na+, K+ -ATPase in concentrations up to 0.1 mM and inhibited its activity in higher concentrations. Mg2+ -ATPase was not influenced up to 0.1 mM concentration, while it was inactivated (40%, P<0.001) in higher CdSO4 concentrations. A dose-response study of brain CdSO4 (1,2 and 5 mg/kg once 8 hr before decapitation) revealed a dose-dependent decrease (-14 to -30%, P<0.001) of brain AChE activity, an increase of Na+, K+ -ATPase activity (+47 to +200%, P<0.001) and an increase of Mg2+ -ATPase only after the highest dose (5mg/kg) in the short-term treatment of rats. Long-term Cd administration (1 mg/kg rat daily for 4 months) activated brain AChE and Na+, K+ -ATPase about 50-65% (P<0.001) but not Mg2+ -ATPase. Brain total antioxidant status was decreased by Cd (30%, P<0.01), while it was increased by L-cysteine or L-cysteine+Cd (50%, P<0.001) in the short-term in vivo treatment. L-cysteine reversed the enzymatic activity changes observed with Cd alone in the high-dose short-term in vivo treatment of rats, as well as the brain AChE inhibition induced by Cd in the in vitro experiments. These results indicate that: a) Cd can influence in a different way the examined enzyme activities after short- and long-term administration, b) Cd may modulate brain cholinergic mechanism(s), neural excitability and metabolic energy production, and c) L-cysteine can have a protective antioxidant effect on the oxidative stress of the brain induced by Cd.