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.     

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.     

端点安全面临重重危机 如何轻松应对

正事实上,绝大多数攻击者是经由用户及其设备进入企业的。现实情况往往是黑客跟踪一个用户,然后此用户成为帮助黑客到达数据库或用户凭据的一个管道。因此,企业不仅需要端点安全和网络安全,而且还要将不同的安全方案集成起来。安全厂商也应当听从时代的召唤,建设针对新威胁的安全方案,迎接深度安全的新时代。     

Sublethal concentrations of mercury in river otters: monitoring environmental contamination

Hair, muscle, and liver mercury concentrations were determined in river otter (Lutra canadensis) carcasses collected from the lower coastal plain and piedmont of Georgia. Mean muscle and hair mercury concentrations were greater (P < 0.001) in otters from the lower coastal plain (4.42 and 24.25 mg/kg wet wt, respectively) compared to otters from the piedmont (1.48 and 15.24 mg/kg, respectively). Liver tissue from lower coastal plain otters averaged 7.53 mg/kg mercury. Mean fetus brain and muscle mercury concentrations were 1.03 and 1.58 mg/kg wet wt, respectively, and fetal muscle mercury concentrations were correlated (r = 0.92) with maternal muscle mercury concentrations. Comparison of mercury concentrations found in Georgia otters to those associated with adverse effects in otter and mink (Mustela vison), indicate sublethal contamination with concentrations in some individuals approaching that observed in experimentally dosed individuals that developed clinical signs of mercurialism. Mercury concentrations in fish from the lower coastal plain approached or exceeded concentrations demonstrated to be toxic to experimentally dosed otters.     

Supplemental Smartamine M or MetaSmart during the transition period benefits postpartal cow performance and blood neutrophil function

The onset of lactation in dairy cows is characterized by severe negative energy and protein balance. Methionine availability during this time for milk production, hepatic lipid metabolism, and immune function may be limiting. Supplementing Met to peripartal diets with adequate Lys in metabolizable protein (MP) to fine-tune the Lys:Met ratio may be beneficial. Fifty-six multiparous Holstein cows were fed the same basal diet from 50 d before expected calving to 30 d in milk. From −50 to −21 d before expected calving, all cows received the same diet [1.24 Mcal/kg of dry matter (DM), 10.3% rumen-degradable protein, and 4% rumen-undegradable protein] with no Met supplementation. From −21 d to expected calving, the cows received diets (1.54 Mcal/kg of DM, 10% rumen-degradable protein, and 5.1% rumen-undegradable protein) with no added Met (control, CON; n = 14), CON plus MetaSmart (MS; Adisseo Inc., Antony, France; n = 12), or CON plus Smartamine M (SM; Adisseo Inc.; n = 12). From calving through 30 d in milk, the cows received the same postpartum diet (1.75 Mcal/kg of DM and 17.5% CP; CON), or the CON plus MS or CON plus SM. The Met supplements were adjusted daily and top-dressed over the total mixed ration at a rate of 0.19 or 0.07% (DM) of feed for MS or SM. Liver tissue was collected on −10, 7, and 21 d, and blood samples more frequently, from −21 through 21 d. Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) with the preplanned contrasts CON versus SM + MS and SM versus MS. No differences in prepartal DM intake (DMI) or body condition score were observed. After calving, body condition score was lower (2.6 vs. 2.8), whereas DMI was greater (15.4 vs. 13.3 kg/d) for Met-supplemented cows. Postpartal diet × time interactions were observed for milk fat percentage, milk fat yield, energy-corrected milk:DMI ratio, and energy balance. These were mainly due to changes among time points across all treatments. Cows supplemented with either Met source increased milk yield, milk protein percentage, energy-corrected milk, and milk fat yield by 3.4 kg/d, 0.18% units, 3.9 kg/d, and 0.18 kg/d, respectively. Those responses were associated with greater postpartum concentration of growth hormone but not insulin-like growth factor 1. There was a diet × time effect for nonesterified fatty acid concentration due to greater values on d 7 for MS; however, liver concentration of triacylglycerol was not affected by diet or diet × time but increased postpartum. Blood neutrophil phagocytosis at 21 d was greater with Met supplementation, suggesting better immune function. Supplemental MS or SM resulted in a tendency for lower incidence of ketosis postpartum. Although supplemental MS or SM did not decrease liver triacylglycerol, it improved milk production-related traits by enhancing voluntary DMI.