Antagonism of the trypanocide,berenil, and the nematocide,morantel, by tubocurarine

Summary The tubocurarine antagonism, (pA₂ values) of acetylcholine, suxamethonium, morantel and berenil were calculated as 6.5, 6.3, 6.4 and 6.2 respectively with the toad rectus abdominis muscle. It is suggested that tubocurarine competitively inhibits the morantel and berenil induced contracture of the toad rectus abdominis muscle.     

Hypertension, the Kuna, and the epidemiology of flavanols

A low sodium diet has often been implicated in the protection of low blood pressure populations from hypertension, but several other dietary factors, including those as yet unidentified, may also be involved. The Kuna Indians of Panama are free of hypertension and cardiovascular disease, but this is changing with migration to urban areas. We compared the indigenous diet of Kuna Indians living on remote islands in Panama (Ailigandi), whose lifestyle is largely hunter-gatherer, with those who have moved to a suburb of Panama City (Vera Cruz). Between April and October 1999, members of a Kuna research team administered a 118-item food frequency questionnaire to133 adult Kuna from Ailigandi and 183 from Vera Cruz. Single 24-hour urine collections and nonfasting blood samples were obtained. The Kuna in Ailigandi reported consuming a 10-fold higher amount of cocoa-containing beverages, 4 times the amount of fish, and twice the amount of fruit as urban Kuna (P<0.05 by t test). Salt added was ample among those living in Ailigandi and Vera Cruz according to both self-report (7.1+/-1.1 and 4.6+/-0.3 tsp weekly) and urinary sodium levels (177+/-9 and 160+/-7 mEq Na/g creatinine), respectively. The low blood pressure of island-dwelling Kuna does not seem to be related to a low salt diet. Among dietary factors that varied among migrating Kuna, the notably higher intake of flavanol-rich cocoa is a potential candidate for further study.     

Comparison of the disposition and of the metabolic pattern of Reboxetine, a new antidepressant, in the rat, dog, monkey and man.

The purpose of this study was to compare the disposition and the metabolic pattern of Reboxetine in several species, including man. [14C]-Reboxetine was given orally to the rat, the dog, the monkey (5 mg/kg) and man (2 and 4 mg/kg). Radioactivity was eliminated both by the renal and faecal route in the rat and the dog, mainly in urine in the monkey and man. Reboxetine was extensively metabolized. A number of urinary metabolites were quantified by radio-HPLC and tentatively identified by comparison with the retention times of reference compounds. Suggested routes of metabolic transformation are: 2-O-dealkylation; hydroxylation of the ethoxyphenoxy ring; oxidation of the morpholine ring; morpholine ring-opening; and combinations of these. Metabolites were partially or completely conjugated with glucuronic acid and/or sulphuric acid.     

Antidepressants, warfarin, and the risk of hemorrhage

BACKGROUND: Case reports suggest that some selective serotonin reuptake inhibitors can interact with warfarin to increase the likelihood of bleeding. We speculated that, among patients receiving warfarin, initiation of selective serotonin reuptake inhibitor treatment would be associated with an increased risk of hospitalization for upper gastrointestinal tract bleeding (UGIB). METHODS: We conducted a population-based, nested, case-control study involving Ontario residents 66 years or older continuously treated with warfarin for at least 1 year. Cases admitted with UGIB were compared with matched controls (1:10) to explore the odds ratio for initiation of various antidepressants within 42, 90, and 180 days before the index admission. RESULTS: From January 1994 to December 2002, we identified 98,784 elderly patients continuously receiving warfarin for at least 1 year; of whom 1538 (0.6%) were admitted to hospital for UGIB. The adjusted odds ratio for fluoxetine/fluvoxamine exposure in 90 days before UGIB hospitalization is 1.2 (95% confidence interval, 0.8-1.7), and the adjusted odds ratio for other selective serotonin reuptake inhibitors in the same period was 1.1 (95% confidence interval, 0.9-1.4). The odds ratios for exposure to antidepressants in 180 days before UGIB hospitalization were similar. CONCLUSION: The initiation of selective serotonin reuptake inhibitor treatment in patients receiving warfarin was not associated with a significant increase in the risk of hospitalization for UGIB.     

Fear, anxiety, and the neuroimaging of PTSD

The clinical manifestations of Posttraumatic Stress Disorder (PTSD) include both fear and anxiety symptoms. Animal studies provide significant information about the neurobiological pathways involved in fear and anxiety and are relevant to the study of PTSD. These studies are reviewed along with Rauch's proposed neurobiologic model for PTSD. Neuroimaging findings in PTSD are summarized by region. Most neuroimaging studies to date have been provocation studies which present a traumarelated stimulus and measure response.While providing information about PTSD, these complex studies were not designed to target specific emotions. Studies which can specifically elicit fear or anxiety and evaluate associated brain regions, such as the bed nucleus of the stria terminalis (BNST) may provide a clearer understanding of the biologic underpinnings of PTSD and bridge the knowledge between animal neurobiology and human studies.     

Thyroid hormone, glucocorticoids, and prolactin at the nexus of physiology, reproduction, and toxicology

A symposium at the 2003 Annual Meeting of the Society of Toxicology brought together an expert group of endocrinologists to review how non-reproductive hormones can affect the endocrine system. This publication captures the essence of those presentations. Paul Cooke and Denise Holsberger recapitulate the evidence of how thyroid hormones affect male and female reproduction, and reproductive development. Ray Witorsch summarizes the many effects of glucocorticoids on the reproductive system. Finally, Paul Sylvester reviews the mechanism of action of prolactin, and reminds us that this ancient hormone has many functions beyond lactation.     

Pharmacological Evaluation of the Anti-inflammatory Activity of a Citrus Bioflavonoid,Hesperidin, and the Isoflavonoids,Duartin and Claussequinone,in Rats and Mice

Abstract— Pretreatment of rats with hesperidin (50 and 100 mg kg^?1, s.c .) reduced the paw oedema induced by carrageenan by 47 and 63%, respectively, within 5 h. The effect was equivalent to that produced by indomethacin (10 mg kg^?1, p.o .), although unrelated to the administered dose, particularly at high doses. At 100 mg kg^?1 hesperidin decreased the rat paw oedema induced by dextran by 33%, without influencing the histamine-induced paw oedema. Hesperidin also inhibited pleurisy induced by carrageenan, reducing the volume of exudate and the number of migrating leucocytes by 48 and 34%, respectively, of control values. Equal doses of duartin and claussequinone were ineffective in all the above tests. Pretreatment of mice with hesperidin (100 mg kg^?1, s.c .) reduced acetic acid-induced abdominal constriction by 50%, but did not affect the tail flick response. Hyperthermia induced by yeast in rats was slightly reduced by hesperidin. No lesions of the gastric mucosae were detected in rats pretreated with hesperidin. The results indicate that hesperidin obtained from citrus cultures may present a potential therapeutical use as a mild antiinflammatory agent, being also useful as a precursor of new flavonoids endowed with such activity.