Effects of gold sodium thiomalate,cyclosporin A,cyclophosphamide, and placebo on collagen-induced arthritis in rats

The prophylactic and therapeutic effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis (CIA) were evaluated in DA rats. Prophylactic treatment with cyclosporin A and cyclophosphamide suppressed the arthritis incidence, clinical inflammation, destructive bone changes, and development of anti-collagen antibody in DA rats subsequently injected with porcine type-II collagen. Therapeutic treatment with cyclosporin A and cyclophosphamide had a definite suppression on established CIA when started 21 days after the initial collagen injection, but the suppression was less marked than that of prophylactic treatment. Gold had no impact on CIA in DA rats when administered either prophylactically or therapeutically.     

A 2-week efficacy and safety study of eszopiclone in elderly patients with primary insomnia

STUDY OBJECTIVES: Evaluate the efficacy of eszopiclone in primary insomnia. DESIGN/SETTING: Randomized, double-blind, placebo-controlled multicenter in outpatient setting with weekly visits. PARTICIPANTS: Two-hundred thirty one men and women aged 65 to 85 years (mean age 72.3 years) with primary insomnia, as defined by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. INTERVENTIONS: Eszopiclone 1 mg (n = 72), eszopiclone 2 mg (n = 79), or placebo (n = 80) nightly for 2 weeks. MEASUREMENTS/RESULTS: Efficacy was assessed using an interactive voice response system. Following the predefined hierarchical testing strategy, the eszopiclone 2-mg group had a significantly shorter sleep latency compared with placebo over the double-blind period (P = .0034). The eszopiclone 2-mg group had significantly longer total sleep time (P = .0003) and eszopiclone 1-mg group had significantly shorter sleep latency (P < or = .012) compared with placebo. The eszopiclone 1-mg group was not significantly different from placebo on total sleep time or any other secondary efficacy endpoint. Secondary analyses indicated that the eszopiclone 2-mg group had significantly less wake after sleep onset; significantly fewer and shorter in duration daytime naps; and significantly higher ratings of sleep quality and depth, daytime alertness, and sense of physical well-being compared with placebo (P < .05). Eszopiclone was well tolerated. The most frequent treatment-related adverse event was unpleasant taste. CONCLUSION: Nightly treatment with eszopiclone 1 mg effectively induced sleep, while the 2-mg dose was effective in inducing and maintaining sleep. Eszopiclone was well tolerated in elderly patients with primary insomnia, and the sleep efficacy was accompanied by significantly less napping and significantly higher ratings of daytime alertness, sense of physical well-being, and several quality-of-life parameters at the higher dose.     

Effects of spaceflight on rhesus quadrupedal locomotion after return to 1G.

Effects of spaceflight on Rhesus quadrupedal locomotion after return to 1G. Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n = 2) or flight simulation at 1G (n = 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a "flexor bias." Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback to the nervous system. Peak MG tendon force amplitudes were approximately two times greater post- compared with preflight or presimulation. Adaptations in tendon force and EMG amplitude ratios indicate that the nervous system undergoes a reorganization of the recruitment patterns biased toward an increased recruitment of fast versus slow motor units and flexor versus extensor muscles. Combined, these data indicate that some details of the control of motor pools during locomotion are dependent on the persistence of Earth's gravitational environment.     

Oxidation of 2-deoxyglucose by human polymorphonuclear leukocytes

Human polymorphonuclear leukocytes (PMNL) can metabolize [l-¹⁴C]2-deoxyglucose to¹⁴CO₂ when stimulated by either phorbol myristate acetate (PMA) or opsonized zymosan. Oxidation of 2-deoxyglucose is about 10–20% as efficient as that of glucose in normal PMNL; it does not occur in defective cells obtained from patients with chronic granulomatous disease. The increased oxidation of [ l-¹⁴C]2-deoxyglucose induced by PMA is not sufficient to explain the inhibition of transport induced by that compound; conversely increased transport of 2-deoxyglucose induced by zymosan-activated serum does not result in a significant increase in oxidation of the hexose. Oxidation of [l-¹⁴C]2-deoxyglucose appears to be mediated by the hexose monophosphate shunt as indicated by the following (1) oxidation of [1-¹⁴C]2-deoxyglucose in intermediate in activity between that of [l-¹⁴C]glucose and [6-¹⁴C]glucose; (2) the reaction is insensitive to cyanide or azide; and (3) shunt enzymes measured in a cell-free extract from human PMNL can react with 2-deoxyglucose compounds with approximately 10% the efficiency shown towards the corresponding glucose derivatives.     

Working conditions and health behavior as causes of educational inequalities in self-rated health: an inverse odds weighting approach

Objective:Using a novel mediation method that presents unbiased results even in the presence of exposure–mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce.Methods:Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50–64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE).Results:Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37–1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15–1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27–1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health.Conclusions:Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.     

Devices for the diagnosis and treatment of temporomandibular disorders. Part I: Introduction, scientific evidence, and jaw tracking

This three-part series of articles summarizes the uses of several devices or groups of devices intended for the diagnosis or treatment of temporomandibular disorders (TMD) and compares their claimed clinical usefulness with the present scientific evidence. Part I of this review defines TMD; discusses the principal criteria for evaluating published scientific clinical evidence such as reliability, validity, sensitivity, and specificity; gives a rationale for the clinical "gold standard" against which diagnostic and therapeutic devices must be compared; and evaluates the status of jaw tracking for the diagnosis of TMD. This review and evaluation led to the conclusion that, at the present time, the claim that jaw-tracking devices have a diagnostic value for TMD is not well supported by the scientific evidence.     

A new class of anti-filariasis compounds: a preliminary look

Parasitic nematode worms which produce filariasis in humans place approximately one billion people at risk in more than 75 countries. More than 100 million people are infected with these diseases and are recognized as being of significant military importance. During World War II, filariasis was among the leading causes of medical evacuation from the entire South Pacific area. Agents available to treat the diseases exhibit significant toxicity. Better drugs are urgently needed. Data are reported from work using a Mongolian jird animal model on a new class of potential drugs, thiosemicarbazones. These compounds exhibit activity against the parasites which cause both lymphatic filariasis and the "onchocerciasis type" of the disease.     

An evaluation of three methods for determining colloid osmotic pressure

Plasma colloid osmotic pressure (COP) is an important determinant in edema formation. Three methods for assessing the COP were evaluated. Direct measurement of COP using the 4420 Wescor Colloid Osmometer was compared to the estimation of COP from both serum total protein and total serum solids (TSS) determinations. Blood samples from twenty adult patients (mean age = 64 years) undergoing cardiopulmonary bypass surgery were collected for COP assessment. Sample collection was performed prior to heparinization/hemodilution, during hypothermic bypass and at the conclusion of bypass following protamine administration. The results obtained from each method were analyzed by a two-way analysis of variance. The Bonferroni technique was used for comparison of sample means when the difference was significant (p less than 0.05). Correlations were reported by linear regression analysis. A statistically significant difference (p less than 0.01) was found between the three methods. A regression equation for the estimation of COP from total serum solids is offered: COP = (3.02 * TSS) + 0.65. Prospective clinical testing between the direct COP measurement and the estimation of COP from TSS using the equation (n = 38) revealed a significant correlation (R2 = .932) and no significant difference between the two (p greater than 0.05).