No abstract

The cardiovascular effects of alpha lipoic acid were evaluated in isolated rat hearts exposed to ischemia-reperfusion injury in vitro. Alpha-lipoic acid raised the level of sulfane sulfur playing an important role in the release of hydrogen sulfide. H2S was shown to prevent the post-reperfusion arrhythmias and to protect the cardiomyocytes from death caused by hypoxia. The activation of potassium ATP-sensitive channels (K(ATP) channels) is one of the most important mechanisms of action of hydrogen sulfide in the cardiovascular system. The aim of this study was to investigate whether alpha lipoic acid can prevent the occurrence of post-reperfusion arrhythmias in vitro using a Langendorff model of ischemia-reperfusion in rats affecting the K(ATP) channels. Alpha lipoic acid significantly improved post-reperfusion cardiac function (reducing incidence of arrhythmias), especially in a dose of 10(-7)M. These cardiovascular effects of this compound on the measured parameters were reversed by glibenclamide, a selective K(ATP) blocker. Alpha lipoic acid increased the level of sulfane sulfur in the hearts. This may suggest that the positive effects caused by alpha lipoic acid in the cardiovascular system are not only related to its strong antioxidant activity, and the influence on the activity of such enzymes as aldehyde dehydrogenase 2, as previously suggested, but this compound can affect K(ATP) channels. It is possible that this indirect effect of alpha lipoic acid is connected with changes in the release of sulfane sulfur and hydrogen sulfide.

Thyroxine (T4), free T4 (fT4), triiodothyronine (T3), free T3 (fT3), reverse T3 (rT3), thyrotropin (TSH), thyroxine binding globulin (TBG), and T3 uptake were measured in 14 chronic alcoholics during withdrawal and after 21 days of abstinence. Results were compared with those of 16 healthy volunteers. During withdrawal, the fT4 and fT3 concentrations were subnormal, whereas the respective protein-bound fractions were normal. T4, T3, and TBG increased during the abstinence period, T3 and TBG being significantly higher than in normals at the second measuring time. T3 uptake values fell, but remained well within the normal range at both measuring times. During abstinence, the fT3 levels remained significantly lower than in healthy subjects. rT3 concentrations decreased, but not significantly. The TSH values were normal throughout. These results showed numerous abnormalities in the hypothalamic-pituitary-thyroid axis in alcoholics, the reasons for which are as yet unclear. The following possible interpretations are suggested: 1. The abnormally low serum fT3 and fT4 levels during withdrawal might reflect an increase in tissue uptake. 2. The increases in T4--and partly those in T3--during abstinence seem to reflect increased binding by TBG, the level of which rose markedly for reasons as yet unknown. 3. If increases in TBG during abstinence are taken into account, the decreases in rT3 concentrations may reach the level of statistical significance. These falls in rT3 concentrations may reflect an increase in rT3 metabolization (deiodination) in various tissues, including the CNS, leading to a reduction in serum rT3 bioavailability. 4. Factors such as liver disease, protein caloric malnutrition, and "psychological stress" do not fully explain all these abnormalities. A direct effect of ethanol on intracellular thyroid hormone metabolism and/or function seems conceivable.

Hepatocytes preincubated for 24 h in the presence of metformin at clinically relevant concentrations showed impaired glycogenesis as well as gluconeogenesis.

The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced αIIbβ3-dependent aggregation (EC50 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcus aureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis.