Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine-induced learning impairment of rats in a 14-unit T-maze

Phenserine ((-)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer.     

Foscarnet penetrates the blood-brain barrier: rationale for therapy of cytomegalovirus encephalitis

Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c.). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET-1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 micrograms/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10(-7) M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell.     

The effect of hole diameter on the torsional mechanical properties of the equine third metacarpal bone

The torsional monotonic structural material properties of equine metacarpi with or without, either a 5/16 inch or 3/8 inch diameter bicortical lateromedial middiaphyseal hole were assessed to determine the effect of a hole on metacarpal strength. Torsional stiffness was not significantly effected by the presence of a bicortical hole, whereas yield and failure angles, torques and energies of metacarpi with a hole were 51% to 97% of those of intact bones. Significant differences were not apparent for yield and failure mechanical properties between metacarpi with a 5/16 inch diameter hole and metacarpi with a 3/8 inch diameter hole; however, postyield mechanical properties were lower for metacarpi with a 3/8 inch hole. Whereas some metacarpi with a 5/16 inch hole were capable of plastic deformation before failure, metacarpi with a 3/8 inch diameter hole appeared to have sufficient stress concentration to propagate complete fracture on structural yield.     

Reliability analysis of k-out-of-n systems with partially repairable multi-state components

In some environments the components might not fail fully, but can lead to degradation and the efficiency of the system may decreases. However, the degraded components can be restored back through a proper repair mechanism. In this paper, we present a model to perform reliability analysis of k-out-of-n systems assuming that components are subjected to three states such as good, degraded, and catastrophic failure. We also present expressions for reliability and mean time to failure (MTTF) of k-out-of-n systems. Simple reliability and MTTF expressions for the triple-modular redundant (TMR) system, and numerical examples are also presented in this study.     

Individual differences in freezing and cortisol in infant and mother rhesus monkeys

Freezing is an adaptive defensive behavior that is expressed in response to an imminent threat. In prior studies with rhesus monkeys, stable individual differences in animals' propensities to freeze have been demonstrated. To understand the factors associated with these individual differences, freezing behavior was examined in infant rhesus monkeys and their mothers, in conjunction with levels of the stress-related hormone cortisol. In both mothers and infants, basal cortisol levels were positively correlated with freezing duration. Additionally, the number of offspring a mother had was negatively correlated with her infant's cortisol level. These findings suggest a link between basal cortisol levels and an animal's propensity to freeze, as well as a mechanism by which maternal experience may affect infants' cortisol levels.     

Primary water stress corrosion cracking inspection ranking scheme for alloy 600 components

The Palisades nuclear plant has developed a comprehensive inspection program to support safe, reliable, and cost-effective operation of all Alloy 600 nozzles and safe ends in the primary coolant system (PCS). As a part of the Palisades Alloy 600 Project, an inspection prioritization scheme was developed to help the plant focus its resources on high-risk components and plan appropriate inspection activities for the other components. The inspection prioritization scheme is based on the susceptibility of the components to primary water stress corrosion cracking (PWSCC), component failure consequences, component leak detectability and component radiation exposure. The scheme provides a simple, systematic and technical base for selecting Alloy 600 components for inspection. The scheme, however, could be used to develop an inspection schedule or to select the highest priority components for mitigation or replacement.     

Current status of monoclonal antibodies for imaging and therapy of prostate cancer

It is clear that there is significant need for improved staging and therapy of prostate cancer. The attributes and strengths of MoAbs seem particularly well-suited to the setting of prostate cancer. Recent progress in the application of MoAbs to in vivo imaging and therapy is encouraging. Clearly, further such efforts in prostate cancer are warranted.