Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat.

Here we assessed the effects of i.g. administration of Zingicomb (ZC), a mixture of zingiber officinale and ginkgo biloba extracts, on learning and memory, and on indicators of oxidative stress in aged rats. Effects of ZC (1 and 10 mg/kg) were investigated in 22-24 months old Wistar rats using the Morris water maze, in which they show deficient performance as compared to 3 months old rats in the undrugged state (days 1 and 2). Treatment was administered on days 3 and 4 of training, then over 7 days with training discontinued, and again on days 5 and 6 when training was resumed. Thereafter chronic treatment was maintained over 5 months. 1 mg/kg ZC improved escape learning in the water maze. The two capital indicators of oxidative stress in brain homogenates, the amount of oxidized proteins (assessed as carbonyl group containing proteins) and lipid peroxidation, were significantly reduced in ZC treated animals. Thus, ZC, which had previously been shown to improve inhibitory avoidance learning and to have anxiolytic properties in adult animals, might also facilitate spatial learning in aged animals, and reduces indices of oxidative stress in brain tissue after chronic treatment.

Proliferating fraction during neoadjuvant chemotherapy of primary breast cancer in relation to objective local response and relapse-free survival.

In women with inoperable primary breast cancer or large T2 tumors, preoperative chemotherapy may induce tumor shrinkage, facilitate surgery and possibly improve survival. However, at present there are no reliable tumor cell parameters to predict which patients will benefit from preoperative chemotherapy. The aims of this study were to analyze the utility of tumor cell proliferation as assessed by Ki-67 staining in fine-needle aspirates from primary breast carcinomas to predict initial response to neoadjuvant chemotherapy as well as recurrence-free survival. The study comprised 51 women with primary breast cancer who received 3-4 courses of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) as neoadjuvant chemotherapy. Tumor cells were procured through fine-needle aspiration biopsy prior to treatment. A second biopsy was performed before the second course of therapy in 33 women. Twenty-nine women (56%) experienced an objective local response after neoadjuvant treatment. During a median follow-up period of 39 months, 21 women (41%) developed disease recurrence. A decrease of more than 25% in proliferating fraction after the first course of chemotherapy correlated significantly with a decreased risk of disease recurrence (p = 0.033) but showed no significant correlation with local objective response. A multivariate analysis revealed that the decrease in proliferating fraction significantly (p < 0.05) added prognostic information to that of involved lymph nodes. These results suggest that changes in proliferating fraction as assessed by Ki-67 staining in fine-needle aspirates during preoperative chemotherapy may be of value in selecting postoperative adjuvant systemic treatment.

Biosynthesis of leukotrienes in canine cerebral vasospasm.

We produced cerebral vasospasm in 29 dogs by the "two-hemorrhage" method of intracisternal injections, 2 days apart, of autogenous arterial blood. Leukotriene (LT) C4, LTD4, and LTE4 were purified from incubated basilar artery, medulla oblongata, hypothalamus, median eminence, and blood clot from around the basilar artery using reverse-phase high-performance liquid chromatography, and the amount of each LT was quantified separately by bioassay with guinea pig ileum. The biosynthetic capacity for total LTs was approximately three times higher in the hypothalamus and median eminence than in the basilar artery and medulla oblongata in the eight normal dogs. In the dogs with subarachnoid hemorrhage, the biosynthetic capacity was increased significantly both before and 2 hours after the second injection of blood on Day 2 and was normal on Day 7 in the basilar artery and medulla oblongata, whereas the biosynthetic capacity was decreased significantly 2 hours after the first and second injections of blood and was increased significantly on Day 7 in the hypothalamus and median eminence. In blood clot the biosynthetic capacity was increased continuously after the first injection of blood. Thus, the biosynthetic capacity for total LTs showed a time- and tissue-specific change after subarachnoid hemorrhage.

Potentiation of vincristine effect in human and murine gliomas by calcium channel blockers or calmodulin inhibitors.

The effects of calcium channel blockers and calmodulin inhibitors on vincristine cytotoxicity were studied in vitro with five glioma cell lines: three human glioblastomas, one rat glioma, and one mouse ependymoblastoma. One human glioblastoma and the rat glioma were resistant to vincristine in contrast to other glioma cells. The resistance to vincristine was considerably decreased by nontoxic or marginally toxic concentrations of calcium channel blockers or calmodulin inhibitors, although the former was more effective than the latter. In the presence of verapamil, the vincristine cytotoxicity, as measured by cell doubling times, increased 90- and 84-fold in the vincristine-resistant human glioblastoma and rat glioma, respectively. The decrease in the resistance to vincristine was related to a marked increase in the intracellular level of that drug, probably mediated by inhibiting its outward transport. The in vivo studies showed that verapamil or nicardipine administered daily with vincristine for 10 days significantly enhanced the chemotherapeutic effect of vincristine in an intracranially transplanted rat glioma model. An approximately 32% to 118% increase in life span occurred with 15 mg/kg/day of verapamil, depending on the doses of vincristine.