Types of acute phase reactants and their importance in vaccination.

Vaccines are considered to be one of the most cost-effective life-saving interventions in human history. The body's inflammatory response to vaccines has both desired effects (immune response), undesired effects [(acute phase reactions (APRs)] and trade-offs. Trade-offs are more potent immune responses which may be potentially difficult to separate from potent acute phase reactions. Thus, studying acute phase proteins (APPs) during vaccination may aid our understanding of APRs and homeostatic changes which can result from inflammatory responses. Depending on the severity of the response in humans, these reactions can be classified as major, moderate or minor. In this review, types of APPs and their importance in vaccination will be discussed.

Testosterone modulation of ethanol effects on the µ-opioid receptor kinetics in castrated rats.

The present investigation was conducted to evaluate the effects of testosterone on ethanol-induced alterations of µ-opioid receptor binding kinetics in specific brain regions of castrated rats. Male Sprague Dawley rats (100-124 g) adapted to a 12-h light/dark cycle were used. Animals were castrated under pentobarbital anesthesia. After a recovery period of 14 days, ethanol [3 g/kg as 22.5% solution in saline via intraperitoneal injection (i.p.)], testosterone [2.5 mg in 0.2 ml of olive oil via subcutaneous injection (s.c.) in the dorsal neck region] or the combination of ethanol and testosterone were administered to rats at 9:00 a.m. The control group was injected i.p. with 2 ml saline and s.c. with 0.2 ml olive oil for 7 days. Animals were sacrificed by decapitation at 2 h after the final injection. The brains were immediately removed, and the cortex, hippocampus, hypothalamus and midbrain were dissected. In an attempt to elucidate the mechanism involved in the hormonal modulation of the effects of ethanol and testosterone on the endogenous opioid system, the binding kinetics of the µ-opioid receptors were determined. The results obtained in the present study assisted in identifying the regulatory role of testosterone on ethanol-induced changes on µ-opioid receptor binding kinetics.

Effect of thalidomide and arsenic trioxide on the release of tumor necrosis factor-α and vascular endothelial growth factor from the KG-1a human acute myelogenous leukemia cell line.

Studies conducted in our lab have indicated that thalidomide cytotoxicity in the KG-1a human acute myelogenous leukemia (AML) cell line was enhanced by combining it with arsenic trioxide. The current investigation was conducted in order to evaluate the effect of thalidomide either alone or in combination with arsenic trioxide on the release of tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) from this cell line in an attempt to clarify its possible cytotoxic mechanism(s). Human AML cell line KG-1a was used in this study. The cells were cultured for 48 h in the presence or absence of thalidomide (5 mg/l), and or arsenic trioxide (4 µM). The levels of TNF-α and VEGF in the supernatant were determined by ELISA. Results obtained indicate that the levels of TNF-α in the supernatant of KG-1a cell cultures incubated with thalidomide, arsenic trioxide, or combination were statistically lower than those observed in the supernatant of control cells (2.89, 5.07, 4.15 and 16.88 pg/ml, respectively). However, the levels of VEGF in the supernatant of thalidomide-treated cells were statistically higher than those in the supernatant of control cells (69.61 vs. 11.48 pg/l). Arsenic trioxide, whether alone or in combination with thalidomide, did not produce any statistically significant difference in the levels of VEGF as compared to the control or thalidomide-treated cell supernatant. These findings indicate that thalidomide and the arsenic trioxide inhibition of TNF-α production by KG-1a cells may play an important role in their cytotoxic effect.

Testosterone reverses ethanol-induced deficit in spatial reference memory in castrated rats.

The present study was designed to evaluate the effects of ethanol, testosterone and combination of ethanol and testosterone, on spatial reference memory and beta-endorphin (beta-EN) levels in castrated rats. Male Sprague-Dawley rats (120-150 g) were used in this study, Animals were castrated and ethanol, testosterone or combination of the drugs were administered to rats at 09:00 h. The drugs were administered after a training period of 5 days and spatial reference memory was evaluated for 7 days using the Morris water maze. One hour after the last injection, animals were sacrificed, their brains removed and dissected into cortex, hypothalamus, hippocampus and midbrain. The beta-EN levels in these brain regions were determined by radioimmunoassay. The time to find the platform (latency period) was significantly increased in ethanol-treated rats, indicating that ethanol induces deficit in spatial reference memory. On the other hand, testosterone administration improved spatial reference memory by significantly decreasing the latency period. In addition, there was a significant decrease in latency period in the animals treated with combination of ethanol and testosterone. Results also indicate that administration of ethanol resulted in a significant increase in beta-EN levels in the hippocampus and in the cortex while concurrent administration with testosterone abolished this increase. These findings clearly indicate that administration of testosterone did not only improve memory but also abolished the spatial memory deficit induced by ethanol in castrated rats.