Anti-platelet aggregation constituents from Formosan Toddalia asiatica

Examination on the wood of Formosan Toddalia asiatica led to the isolation of 30 compounds, including coumarins, alkaloids, a benzoquinone and an amine. Among the isolates, (+/-)-toddanin and (-)-isocoreximine are new compounds, while cyclohexylamine was isolated for the first time from nature. The structures of the compounds were elucidated from spectroscopic data and chemical evidence. Bioassay-guided fractionation led to the isolation of seven compounds showing strong anti-platelet aggregation activity in vitro.     

Chronic desipramine treatment desensitizes the rat to anesthetic and antinociceptive effects of the alpha2-adrenergic agonist dexmedetomidine

INTRODUCTION: The effects of long-term administration of the tricyclic antidepressant agent desipramine on the hypnotic, antinociceptive, anesthetic-sparing, and central norepinephrine turnover suppressant action of short-term dexmedetomidine, a highly selective alpha2-adrenergic agonist, were studied in rats. METHODS: Rats were given a 3- or 4-week course of twice daily administration of desipramine, 10 mg/kg, or saline. The effect of a hypnotic dose of dexmedetomidine, 250 microg/kg given intraperitoneally, on the duration of loss of righting reflex was determined. The tail flick latency response was determined before and after 50 microg/kg dexmedetomidine. The minimum anesthetic concentration of halothane and the central norepinephrine turnover rate were determined before and after administration of 30 microg/kg dexmedetomidine. Changes in the affinity and density of the alpha2-adrenergic receptor in locus coeruleus and spinal cord also were determined. RESULTS: Treatment with desipramine decreased dexmedetomidine-induced loss of righting reflex duration by 67% and eliminated the antinociceptive effect of dexmedetomidine. Dexmedetomidine produced a 55% decrease in minimum anesthetic concentration in the control group but no reduction in desipramine-treated rats. Desipramine did not change the receptor density or binding affinity of alpha2 receptors at the site for hypnotic (locus coeruleus) or antinociceptive (spinal cord) responses. No decrement in the central norepinephrine turnover rate was noted in the locus coeruleus of dexmedetomidine after 3 weeks of treatment with desipramine. The alpha1-adrenergic antagonist prazosin at 1 or 5 mg/kg completely (minimum anesthetic concentration reduction), almost completely (antinociceptive), or partially (hypnotic) restored responsiveness to normal. CONCLUSIONS: These data indicate that treatment with desipramine induces hyporesponsiveness to the hypnotic, analgesic, and minimum anesthetic concentration-reducing, but not to the suppression of central norepinephrine turnover, properties of dexmedetomidine. The hyporesponsiveness appears to involve an alpha1-adrenergic mechanism.     

Brain activation during an auditory ''oddball task'' in schizophrenia measured by single photon emission tomography

When infants are weighed at well baby or infant welfare clinics, the weight change from one visit to the next is used as a guide to the welfare of the child. Infant welfare clinic nurses are expert clinicians who use weight measurements as a rough indicator of well-being only, as it is well known by them that these measurements are fraught with error. This paper calculates the amount of error which was found in repeated tests of weights of infants, and in the weight changes brought about by biological variation. As a result, it is recommended that babies under nine months of age be weighed at clinic visits no less than a fortnight apart, and older infants, at least one month apart. If they are weighed more often, then the weight changes detected will be less than the amount of error which affects the measurements.     

Resistance to radiation-induced apoptosis in Burkitt's lymphoma cells is associated with defective ceramide signaling

Increased sensitivity to ionizing radiation has been shown to be due to defects in double-strand break repair and mutations in the proteins that detect DNA damage. However, it is now recognized that the cellular radiation response is complex and that radioresistance/radiosensitivity may also be regulated at different levels in the radiation signal transduction pathway. Here, we describe a direct relationship between resistance to radiation-induced apoptosis and defective ceramide signaling. Radiation sensitivity in human tumor cells correlated with the immediate accumulation of the second messenger ceramide. In the BL30A Burkitt's lymphoma line, ceramide increased 4-fold by 10 min postirradiation (10 Gy), and in the moderately sensitive HL-60 leukemia cells, ceramide accumulated 2.5-fold above basal levels. In contrast, in all radioresistant tumor cells examined, including several Burkitt's lymphoma lines (BL30K, BL29, and BL36) and the MO59K glioma cell line, ceramide did not accumulate postirradiation. The ability to abrogate ceramide production by pretreatment with the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, conferred resistance to radiation-induced apoptosis in the sensitive BL30A cells. An isogenic subline of BL30A, BL30K, was resistant to both C8-ceramide (20 microM) and ionizing radiation-induced apoptosis. Bypassing the block in radiation-induced ceramide production by the addition of exogenous ceramide was not sufficient to induce apoptosis; this suggests the existence of a second ceramide-associated signaling defect in these radioresistant cells that confers resistance to ceramide-induced apoptosis. Thus, these results provide compelling evidence that ceramide is an essential mediator of radiation-induced apoptosis and that defective ceramide signaling confers an apoptosis-resistant phenotype in tumor cells.     

Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer

The taxanes represent a new class of clinical chemotherapeutic agents. A series of in vitro studies were independently of each other initiated in two different institutes (Amsterdam and Madison) to test the hypothesis that hyperthermia might enhance the cytotoxicity of taxanes. Clonogenic capacity experiments (Amsterdam) included the exposure of R1- and SW 1573-cells to 1, 4, or 24 h of paclitaxel with heat 43 degrees C x 60 min in the last hour of drug treatment or at 24, 48 as well as 72 h post drug treatment. Survival assay experiments (Madison) included the exposure of L-929-cells to paclitaxel and docetaxel for 24 h with heat 41.8 degrees C x 60 min the first or last hour of drug treatment as well as 24 and 48 h post treatment. No thermal enhancement of cytotoxicity for the taxanes was observed in these human and murine cell lines, with congruent data in both institutes. In addition, high performance liquid chromatography studies at 41.8 degrees C and 43 degrees C demonstrated paclitaxel and docetaxel were heat stable.     

Aneurysm of superficial temporal artery in angiolymphoid hyperplasia lesions

Parent or self-reported history of fractures in a group of patients aged from 0.3 to 33.6 years on dietary treatment for phenylketonuria was studied by means of a questionnaire. Twenty-one of 85 patients had a history of fracture compared with 18/98 sibling controls. There was no significant difference in the lifetime risk of fracture between patients and controls (chi 2 = 1.43, df = 1, p = 0.23), but a significantly higher risk of fracture was reported over the age of 8 y (chi 2 = 5.11, df = 1, p = 0.024), with a relative risk of 2.6 (95% confidence interval 1.1.6.1). We suggest this may be related either to deterioration in dietary control in this age group or to a cumulative disease-related or diet-related reduction in bone mass.     

Influence of tempering on the feeding value of rolled corn in finishing diets for feedlot cattle

Crossbred yearling steers (n = 125; 372 kg) were used in a 109-d finishing trial. Steers were fed an 88% concentrate diet containing 65% corn (DM basis) as 1) dry rolled corn (DRC); 2) tempered rolled corn (TRC), 43 mg surfactant (SarTemp)/kg corn; 3) TRC, 172 mg surfactant/kg corn; 4) TRC, 430 mg surfactant/kg corn; and 5) steam-flaked corn (SFC). Corn moisture was greater (3.5%, P < .01) for TRC than for DRC but less (10%, P < .05) than for SFC. Starch enzymatic reactivity was less for TRC than for either DRC (18%, P < .05) or SFC (42%, P < .01). Tempering increased the integrity of rolled corn and reduced the amount of particles less than 2 mm in diameter by 54% (P < .01). Steam flaking corn increased (P < .01) proportion (78%) of the grain having a particle size distribution of greater than 8 mm, as compared with TRC (25%) and DRC (3%). Compared with DRC, tempering enhanced (P < .10) ADG (9%), feed efficiency (5%), and dietary NE (3%). Daily weight gain was similar (P > .10) for TRC and SFC. Feed efficiency (P < .10) and dietary NE (P < .01) were greater (6%) for SFC than for TRC. There were no differences (P > .10) between DRC and TRC in ruminal and total tract digestion of OM, N, and starch, and in ruminal microbial efficiency. Ruminal digestion of OM decreased (linear effect, P < .05) and ruminal microbial efficiency increased (linear effect, P < .05) with increasing surfactant concentration. Ruminal digestion of OM and starch, and flow of nonammonia N to the small intestine were greater (31, 56, and 14%, respectively, P < .01) for SFC than for TRC. Postruminal and total tract digestion of OM, N, and starch, and dietary DE were greater (P < .01) for SFC than for TRC. We concluded that tempering corn will enhance animal performance. Increasing the concentration of surfactant used in tempering may enhance ruminal microbial efficiency and lean tissue growth.