Abstract: The PI3K/AKT and RAS/RAF/MEK/ERK signaling pathways are often activated concurrently by separate genetic alterations in human cancer. Although the selective advantage of mutational activation of both pathways remains largely elusive, emerging evidences indicate that both pathways interact to regulate each other and cooperate to maintain the transformed phenotype and promote cancer progression and metastasis. Here, we focus on recent findings on the convergent regulation of downstream functions by AKT and ERK pathways and discuss the biologic and therapeutic relevance of the pathway convergence in cancer.

Abstract:
Objectives: Khat (Catha edulis forsk; family: Celastraceae) is a plant habitually chewed by several millions of people in Yemen and southern east areas of Africa for its pleasant stimulant effect on physical activity, consciousness, motor and mental functions as well as its anti-fatigue action. This study was aimed to investigate the implication of chronic khat-habituation on secondary generalized seizures in an animal model.
Methods: Eighteen mice (20-30gm) were used in this study; they were grouped into control, Khat-habituated, and khat-withdrawal. Khat-habituation was induced by providing khat (2g/kg) with food for two months. Khat-withdrawal was induced by cessation of khat-containing food for 14 days. Secondary generalized seizures resemble those occurring in human brain were induced in animals by kindling which was performed by repeated intraperitoneal injection of sub-convulsive doses (11.5mg/kg) of INH at intervals of 30 minutes. The intensity of seizures was determined by empirical scale modified from the behavior scale grading. The latency periods for development of seizures were observed.
Results: Khat-habituated animals showed no epileptic activity all through the experimental period. However, they showed significant decrease in the threshold dose of INH to produce epilepsy, increase in intensity and decrease in latency period of 2ry generalized epileptic seizures induced by INH-kindling. Khat-withdrawal for 14 days reversed effects of khat-habituation on epilepsy.
Conclusion: Chronic khat-habituation in mice resulted in decreased latency period for development of secondary generalized seizures and increased intensity of seizures, this effect may be reversed after its cessation.

Abstract: Rosmarinus officinalis Linn. has several therapeutic applications in folk medicine and carnosic acid is one of the major chemical constituents in this plant. Standardized extract of Rosmarinus officinalis (ROE) and carnosic acid (CA) isolated from Rosmarinus officinalis were evaluated for anxiolytic-like activity. Methods used were elevated plus maze, open field and social interaction tests. Charles foster albino rats were treated with ROE at the doses of 30, 100 and 300 mg/kg/day and CA at the doses of 5, 15 and 45 mg/kg/day, p.o. for seven consecutive days respectively. In all tests, ROE and CA exhibited significant anxiolytic activity. ROE and CA significantly increased the level of 5-hydroxy tryptamine and dopamine concentration in rat brain while norepinephrine concentration was decreased. These results suggest that both ROE and CA has significant anxiolytic effect in dose dependent manner and qualitatively similar to standard anxiolytic agent lorazepam, which likely to regulated through monoaminergic system in the brain. These observations strongly suggest that carnosic acid seems to be major active constituent of RO for its observed anxiolytic activity in rodents.

Abstract: A total of twenty subjects were enrolled in the study to find the lowest oral dose of drug in which the parent compound and/or one of the two major metabolites would be reliably detected in 80% of the urine samples. Five subjects received 5mg and fifteen received 2mg for 5 days of observed dosing with urine sampled on days 1, 4 and 5. OPC3373 was found in 93% of the samples compared to 50% for aripiprazole and 8% for dehydroaripiprazole. Aripiprazole serum samples on days 1 and 5 were similar indicating that steady state had been achieved. This information is consistent with the subjects being adherent to their prescribed dosing at study entry. In conclusion, urine levels of OPC3373 appear to be the most reliable marker for monitoring compliance with aripiprazole.