Elucidation of mitochondrial effects by tetrahydroaminoacridine (tacrine) in rat, dog, monkey and human hepatic parenchymal cells

Tetrahydroaminoacridine (tacrine) causes morphological and functional changes in the endoplasmic reticulum, ribosomes, and mitochondria in the liver of humans and animals. In order to investigate species differences as well as to understand the morphological changes, we examined the effects of tacrine on respiration and electron transport in mitochondria isolated from rat, dog, monkey, and human liver. Tacrine produced significantly decreased respiratory control ratios (RCR) in all species at concentrations ranging from 5 to 25 microg/ml. Human mitochondria were more sensitive to tacrine effects with RCR decreased 24% at 5 microg/ml while other species were unaffected at this concentration. The tacrine effects were characterized by increased hepatic mitochondrial State 4 respiration in rats and decreased State 3 respiration in humans. Mitochondria from aged rats were more sensitive to the effects of tacrine than mitochondria from young animals, with significantly decreased RCR at 10 microg/ml in aged rats while mitochondria from young rats were unaffected at this concentration. Concomitant with the respiratory changes, mitochondrial DNA synthesis was impaired. Since tacrine undergoes extensive biotransformation, we also explored the possibility that metabolites could exert detrimental effects. The ranking order of potency for decreasing RCR caused by monohydroxylated metabolites was: tacrine > 4-OH and 7-OH > 2-OH, 1-OH, and velnacrine with the latter group of metabolites having no effect on mitochondrial respiration at concentrations up to 50 microg/ml. In vivo administration of 20 mg/kg tacrine to rats for up to 20 days caused a paradoxical increase in RCR and P/O on Day 1 and decreased RCR on Days 9 and 20, the later findings being consistent with in vitro data. From these data we propose that tacrine does not necessarily have to be metabolized to exert effects on mitochondria at different sites in the electron transport chain that differ among species. These effects are exacerbated in mitochondria from older animals and humans appear to be more sensitive than the laboratory animals studied.     

Lingual ischemia following tongue entrapment in a glass bottle

A 10-year-old, previously healthy female presented to the emergency department via emergency medical service transport, with her tongue tightly entrapped inside a glass bottle (9 oz, Yoohoo brand of chocolate drink). The tongue was massively edematous and ecchymotic due to impaired venous return from constriction by the neck of the bottle. After repeated attempts at mechanically reducing the tongue out of the bottle, a professional glazier was contacted, who was able to remove the bottle in the operating room with a steel glass cutter. Needle evacuation of a small hematoma was then performed to decrease the pressure ischemia to the tongue, which began to improve quickly.     

Does the Youth Corrections System Work? Tracking the Effectiveness of Intervention Efforts With Delinquent Boys in State Custody.

This study adopted a systemic approach to studying intervention efforts with delinquent youth, examining the association between several youth corrections programs and adult criminal outcomes. Two studies were designed to use juvenile and adult court records to evaluate the effectiveness of treatment programs provided to delinquent youth in state custody. The results of Study 1 suggested that court-recorded delinquent charges can be used to estimate delinquency severity. The results of Study 2 presented a discouraging but not entirely unexpected illustration of the effectiveness of intervention efforts among delinquent youth. It was found that time spent in juvenile detention facilities, work programs, and group homes was associated with negative adult criminal outcomes. No links between time spent in youth corrections programs and positive outcomes were identified. Implications for future program evaluation efforts are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Percutaneous transjejunal biliary intervention: 10-year experience with access via Roux-en-Y loops

Ancylostoma duodenale is still the dominant hookworm species in the Mediterranean area, India, China and Japan. In the present study, biopsied materials were taken from the small intestine of 30 patients infected only with A. duodenale and 12 cross matched controls. The results showed some pathological changes in severely infected cases. However, normal or insignificant changes were seen in the enzymatic activity of the intestinal mucosa.