Stable Anticonvulsant Action of Benzodiazepines During Development in Rats

Abstract— The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg^?1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0·1 and 0·02 mg kg^?1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.     

Relative Immunogenicity and Tolerogenicity of Individual Regions or Segments of the MHC

Mixed lymphocyte culture (MIX) reactivity, induction of cytotoxicity in vitro, survival of skin allografts, and induction of neonatal transplantation tolerance were compared in mice of the strain combinations differing in the entire H-2 complex or in individual segments of it. The results showed that antigenic products of the K end of the H-2 complex were more immunogenic and also more resistant to tolerance induction than the products of the D end of H-2. I-region products that elicited transplantation reactions of variable strength, depending on the detection system, were relatively easier to overcome in tolerance induction and could, at least in some combinations, contribute to tolerance induction across the barrier represented by the products of the K region of the H-2 complex.     

Enterostomy in Patients with Primary Neuropathic Amyloidosis

Three patients with primary neuropathic amyloidosis are reported. They were all almost totally disabled by either diarrhea and incontinentia alvi or obstipation. In all three patients enterostomies were tried as a palliative treatment and the results of the operations have been very promising.     

An Evaluation of the Protective Effects of Thymoquinone on Amikacin-Induced Ototoxicity in Rats

Objectives

In this study we investigated the probable protective effects of thymoquinone on amikacin-induced ototoxicity in rats.

Methods

Thirty-two healthy rats were divided into four groups (amikacin, amikacin+thymoquinone, thymoquinone, and no treatment). Thymoquinone was fed to the rats via oral gavage in a dose of 40 mg/kg/day throughout the study period of 14 days. Amikacin was given by the intramuscular route in a dose of 600 mg/kg/day. Audiological assessment was conducted by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests, administered to all rats at the beginning of the study, and also on days 7 and 15. Biochemical parameters were calculated at the termination of the study to evaluate the oxidative status.

Results

There were significant decreases in DPOAE values and significant increases in ABR thresholds of the amikacin group on days 7 and 15, as compared to the amikacin+thymoquinone group. While ABR thresholds of the amikacin group increased significantly on days 7 and 15 as compared to their initial values, there were no significant differences between the initial and the 7th and 15th day values of ABR thresholds in the amikacin+thymoquinone group. Total oxidant status and oxidative stress index values of the amikacin+thymoquinone group were significantly lower than those of the amikacin group. Total antioxidant status values of the amikacin+thymoquinone group were significantly higher than those of the amikacin group.

Conclusion

Our study has demonstrated that the ototoxic effect brought forth by amikacin could be overcome with the concurrent use of thymoquinone.