Repeated contact with subtoxic soman leads to synaptic vulnerability in hippocampus

Soman, an anticholinesterase and dangerous nerve agent, produces convulsions, memory impairment, and cell loss in the brain, especially in the hippocampus. Soman-induced accumulation of acetylcholine initiates mechanisms responsible for the development of incapacitating seizures. The prolonged epileptiform nature of these seizures causes the release of another excitatory neurotransmitter, glutamate, which has been linked to the toxic action of the nerve agent. Here, we tested whether subtoxic soman exposures influence the brain's sensitivity to glutamate-based excitotoxicity. Over a 1-week period, hippocampal slice cultures were exposed daily to a transient level of soman that produced no evidence of synaptic deterioration. After the subtoxic soman treatments, however, the tissue became vulnerable to a brief episode of glutamate receptor overstimulation that normally resulted in little or no excitotoxic damage. In those slice cultures treated with subtoxic soman, a decline in synaptic markers as well as an increase in spectrin breakdown occurred 24 hr after the mild excitotoxic event. Exposure to high soman concentrations alone produced similar synaptic degeneration, but without evident cell death, suggesting that synaptic decline is an early neurotoxicological response to the nerve agent. Interestingly, enhanced excitotoxic sensitivity caused the brain tissue to become susceptible to disparate insults initiated before or after the soman contact. These findings indicate that seemingly innocuous soman exposures leave the hippocampus sensitive to the types of insults implicated in traumatic brain injury and stroke. They also warn that asymptomatic contact with soman may lead to progressive synaptopathogenesis and that early indicators of soman exposure are critical to prevent potential brain injury.     

Cholesterol metabolism in 8 to 12-year-old children born preterm or at term

Studies in animals have indicated that cholesterol metabolism is susceptible to manipulation by diet and growth in early life. In humans, low birthweight has been associated with increased risk of coronary heart disease. AIM: To establish whether plasma lipids and indicators of cholesterol absorption, synthesis and breakdown differ in children born preterm and at term. METHODS: Plasma total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triacylglycerols, apolipoprotein A1, apolipoprotein B, lathosterol (indicator of cholesterol synthesis), campesterol (indicator of cholesterol absorption), 7-alpha hydroxycholesterol (indicator of cholesterol breakdown) were measured in up to 407 children born preterm and 36 children born at term. RESULTS: Children born preterm had lower cholesterol synthesis (p = 0.002) and lower cholesterol breakdown (p < 0.001) than those born at term, but their plasma cholesterol concentration was not significantly different. After adjusting for current size, birthweight and gestational age were significantly related to plasma lathosterol and 7-alpha hydroxycholesterol. However, when both birthweight and gestational age were adjusted, only gestational age remained significant. There were no significant differences in plasma campesterol between the two groups. CONCLUSION: Being born preterm may have a long-term effect on cholesterol metabolism in children 8-12 y later. Those born prematurely had lower cholesterol synthesis and breakdown, but their plasma cholesterol concentration was similar at this age. These parameters need to be studied in older cohorts.     

DIF-1, an anti-tumor substance found in Dictyostelium discoideum,inhibits progesterone-induced oocyte maturation in Xenopus laevis

Differentiation-inducing factor-1 (DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one) is a putative morphogen that induces stalk-cell formation in the cellular slime mold Dictyostelium discoideum. DIF-1 has previously been shown to suppress cell growth in mammalian cells. In this study, we examined the effects of DIF-1 on the progesterone-induced germinal vesicle breakdown in Xenopus laevis, which is thought to be mediated by a decrease in intracellular cAMP and the subsequent activation of mitogen-activated protein kinase (MAPK) and maturation-promoting factor, a complex of cdc2 and cyclin B, which regulates germinal vesicle breakdown. DIF-1 at 10–40 μM inhibited progesterone-induced germinal vesicle breakdown in de-folliculated oocytes in a dose-dependent manner. Progesterone-induced cdc2 activation, MAPK activation, and c-Mos accumulation were inhibited by DIF-1. Furthermore, DIF-1 was found to inhibit the progesterone-induced cAMP decrease in the oocytes. These results indicate that DIF-1 inhibits progesterone-induced germinal vesicle breakdown possibly by blocking the progesterone-induced decrease in [cAMP]_i and the subsequent events in Xenopus oocytes.     

The pathogenic activation of calpain: a marker and mediator of cellular toxicity and disease states

Over-activation of calpain, a ubiquitous calcium-sensitive protease, has been linked to a variety of degenerative conditions in the brain and several other tissues. Dozens of substrates for calpain have been identified and several of these have been used to measure activation of the protease in the context of experimentally induced and naturally occurring pathologies. Calpain-mediated cleavage of the cytoskeletal protein spectrin, in particular, results in a set of large breakdown products (BDPs) that are unique in that they are unusually stable. Over the last 15 years, measurements of BDPs in experimental models of stroke-type excitotoxicity, hypoxia/ischemia, vasospasm, epilepsy, toxin exposure, brain injury, kidney malfunction, and genetic defects, have established that calpain activation is an early and causal event in the degeneration that ensues from acute, definable insults. The BDPs also have been found to increase with normal ageing and in patients with Alzheimer's disease, and the calpain activity may be involved in related apoptotic processes in conjunction with the caspase family of proteases. Thus, it has become increasingly clear that regardless of the mode of disturbance in calcium homeostasis or the cell type involved, calpain is critical to the development of pathology and therefore a distinct and powerful therapeutic target. The recent development of antibodies that recognize the site at which spectrin is cleaved has greatly facilitated the temporal and spatial resolution of calpain activation in situ. Accordingly, sensitive spectrin breakdown assays now are utilized to identify potential toxic side-effects of compounds and to develop calpain inhibitors for a wide range of indications including stroke, cerebral vasospasm, and kidney failure.     

Lateral breakdown of nonendodontic origin adjacent to maxillary left incisors

CASE REPORT: A 16-year-old female presented with a labial fistula located between the central and lateral left maxillary incisors. The teeth had normal colour, responded positively to pulp testing, demonstrated negative percussion tests and had no evidence of periodontal pockets. The patient reported no history of trauma, but mentioned that she had received orthodontic treatment. Radiographic examination showed bone loss between these two teeth. Explorative surgery followed by antibiotic treatment was performed, but a fistula reappeared after 22 months. Surgical retreatment combined with antibiotic treatment resulted in gradual healing over a three-year period. No root canal treatment was performed. Aetiological considerations connected to tissue injury and inflammation are discussed. Inflammation induced disturbances in local homeostasis may possibly explain the lateral breakdown of bone. Such areas of reduced resistance may, under unfavourable conditions, be infected by blood-born pathogens. Information about such aberrant cases is important in endodontic decision making.     

Intra-operative epidural blockade with local anaesthetics and postoperative protein breakdown associated with hip surgery in elderly patients

The effect of epidural anaesthesia of limited duration on postoperative protein breakdown was studied in elderly patients undergoing hip arthroplasty. Two groups of six patients each were studied. One group with halothane (C) and one with an epidural block, T8-S4, (E) as part of their general anaesthetic for surgery. The urinary excretion of urea nitrogen and 3-methylhistidine (3-MeH), an indicator of muscle protein breakdown, increased significantly in both groups after surgery, by the same amount (P less than 0.05). The total concentration of plasma and muscle aminoacids decreased after surgery in both groups. Muscle glutamine was decreased by 50% after surgery on the fourth postoperative day in both groups (P less than 0.05). Therefore epidural anaesthesia, limited to the period of surgery, did not attenuate the loss of body proteins which occurred during the postoperative period.     

Direct and indirect effects of electrical stimulation on the motility of human sperm

BACKGROUND: Electroejaculation is a technique that is becoming more frequently available for obtaining sperm from men with spinal cord injury or psychogenic anejaculation. However, the effect of electrical stimulation on the movement of human sperm has not been clarified. METHODS: Electrical stimulation was applied to ejaculated semen or washed sperm via a pair of electrodes in the sperm-counting chamber while sperm motility was recorded using a computer-assisted semen analyzer. RESULTS: When monopolar pulse stimulation was applied to sperm, the motility rate and velocity of sperm near both electrodes decreased according to the number of pulses and current despite low electrical voltages. However, motility of sperm in the center between electrodes did not change. When extremely high-voltage electrical stimulation with more than 80 V/2 mm (distance between electrodes) was applied to sperm, sperm stopped moving regardless of their location between the electrodes, despite a low electrical current and low energy. Replicating clinical rectal probe electroejaculation, continuous sinusoidal alternating current at 50 V/10 mm was applied to a untreated ejaculated semen. The motility of sperm, except for those adjacent to both electrodes, did not change after stimulation for 60s, despite a high electrical energy. CONCLUSIONS: The motility of sperm near electrodes was decreased when high electric current flowed, despite low electrical voltages. In addition, sperm lost their motility when extremely high-voltage electrical stimulation was applied. However, electrical stimulation during clinical rectal probe electroejaculation seems to have no effect on sperm motility.     

Determination of Trace Metals Using Laser Induced Breakdown Spectroscopy in Insoluble Organic Materials Obtained from Pyrolysis of Plastics Waste

Laser induced breakdown spectroscopy (LIBS) was applied for the detection of trace elements in non-degradable part of plastics known as insoluble organic material, obtained from thermal and catalytic degradation of plastics. LIBS signal intensity for each metal measured in the test sample was unique and different. The capability of this technique is demonstrated by analyzing various trace metals present inside plastics and also compared with ICP results. The metal concentration (ppm) measured with LIBS and verified by ICP for Ag (901), Al (522), Fe (231), Co (628), V (275), Ni (558), Pb (325), Mn (167) and Cd (378) are higher than permissible safe limits.     

ATL Ultramark 9HDI B超直流变换器故障原理及检修

本文介绍了ATL UM9HDI B超直流变换器的工作原理、常见故障及检修的方法。     

The effect of amino acid infusion on leg protein turnover assessed by L-[15N]phenylalanine and L-[1-13C]leucine exchange

A stable isotope technique depending on the use of [15N]phenylalanine and [1-13C]leucine to assess exchange was utilized to measure the components of protein turnover of the human leg and the effects of amino acid infusion. Eight healthy subjects (28.5 +/- 2.5 years) were studied when post-absorptive in the basal state and again during infusion of a mixed amino acid solution (55 g l-1, 1.52 ml kg-1 h-1). During the basal period leucine oxidation by the leg was 4.4 +/- 2.0 nmol 100 g-1 min-1 and this increased threefold during amino acid infusion (13.6 +/- 3.1 nmol 100 g-1 min-1, mean +/- SEM, P = 0.003). Amino acid infusion abolished the net negative balance between incorporation of leucine into, and release from, protein (basal, -31.8 +/- 5.8; during infusion, +3.1 +/- 7.1 nmol 100 g-1 P = 0.001). Phenylalanine exchange showed a similar pattern (basal, -13.7 +/- 1.8; during infusion, -0.8 +/- 3.0 nmol 100 g-1 min-1, P = 0.003). Basal entry of leucine into leg protein (i.e. protein synthesis) was 70.0 +/- 10.8 nmol 100 g-1 min-1 and this increased during amino acid infusion to 87.3 +/- 14.1 nmol 100 g-1 min-1 (P = 0.11). Phenylalanine entry to protein also increased with amino acid infusion (29.1 +/- 4.5 vs. 38.3 +/- 5.8 nmol 100 g-1 min-1, P = 0.09). Release from protein of leucine (101.8 +/- 9.1 vs. 84.2 +/- 9.1 nmol 100 g-1 min-1, P = 0.21) and of phenylalanine (42.8 +/- 4.2 vs. 39.1 +/- 4.2 nmol 100 g-1 min-1, P = 0.50) was unchanged by amino acid infusion. The results suggest that, in the post-absorptive state in man, infusion of mixed amino acids, without additional energy substrates; reverses negative amino acid balance by a mechanism which includes stimulation of muscle protein synthesis but which does not alter protein breakdown. Interpretation of the results obtained concurrently on whole-body protein turnover suggests that the increase in muscle protein synthesis contributes substantially to the whole-body increase, but the fall in whole-body breakdown with exogenous amino acids is independent of changes in muscle.