The feeling of fatigue--fatigue severity by unidimensional versus composite questionnaires

The authors' purpose in this study was to compare the perception of fatigue severity as measured by different fatigue questionnaires. The authors evaluated 3 groups of patients in a cross-sectional study: chronic fatigue syndrome (CFS, n = 20), non-CFS fatigue (n = 20), and familial Mediterranean fever (FMF n = 25). In addition, the authors tracked 7 patients with CFS longitudinally for severity of fatigue. The severity of fatigue-related symptoms was assessed with 2 questionnaires: the unidimensional Chalder's Fatigue Severity Scale (CH) and the composite Fatigue Impact Scale (FI) which has 3 subscales--cognitive, physical, and social--and a total score. In the cross-sectional study, correlations between CH and FI cognitive scores were r = .78 (p < .0001), CH versus FI physical scores r = .603 (p < .0001), CH versus FI social scores r = .66 (p < .0001), and CH versus FI total scores r = .74 (p < .0001). In the longitudinal survey of CFS patients, the authors compared 30 questionnaires revealing correlations of CH versus FI cognitive scores r = .64 (p = .0004), CH versus FI physical r = .68 (p = .0001), CH versus FI social r = .87 (p < .0001), and CH versus FI total r = .90 (p < .0001). Fatigue severity as assessed by the unidimensional CH scale and the composite FI scale is comparable. The simple CH scale may be adequate for the assessment of the feeling of fatigue, in general, and for monitoring the severity of fatigue in CFS, in particular.     

Relationship between antidepressants and IGF-1 system in the brain: Possible role in cognition

Antidepressants facilitate neuroplasticity by stimulating trophic factors. This study evaluated the effect of fluoxetine (FLX) treatment on insulin-like growth factor-1 (IGF-1) in the rat brain and its role in the effect of FLX on cognition. IGF-1 receptor (IGF-1R) protein expression and IGF-1 mRNA levels were assessed in rat frontal cortex (FC) and hippocampus, in FLX-treated [15 mg/kg, orally; 3 (acute) or 21 (repeated) days] male Wistar rats. Rats were subjected to the Morris Water Maze test. Acute FLX administration decreased IGF-1 mRNA levels in the FC and hippocampus and increased IGF-1R levels in the FC. Repeated FLX increased both mRNA and IGF-1R levels in the FC. Repeated, but not acute, FLX treatment decreased IGF-1 mRNA in the hippocampus. FLX did not affect cognitive performance. Thus, repeated FLX treatment leads to upregulation of IGF-1 system is FC. It is possible that FLX affect FC neuroplasticity through activation of the IGF-1 system.     

Perindopril, atenolol, and amlodipine prevent aortic ultrastructural changes in rats exposed to ethanol.

BACKGROUND: The effects of perindopril, an angiotensin-converting enzyme inhibitor, atenolol, a beta adrenergic receptor blocker, and amlodipine, a calcium channel blocker, were investigated in chronic alcohol administered rats. MATERIAL/METHODS: Adult male Wistar rats (240-320 g) were used in the present study. Alcohol was given to rats on a modified liquid diet for 21 days. Perindopril (2.5 and 5 mg/kg), atenolol (5 and 10 mg/kg), and amlodipine (5 and 10 mg/kg) were injected into rats in different groups intraperitoneally for 21 days. Control rats were pair fed an isocaloric liquid diet containing sucrose as a caloric substitute for alcohol. Saline was injected into the control rats for 21 days. The hearts were removed after the rats were anesthetized by ether, and 1-mm3 samples from the ascending aortas were fixed. Five fields per aorta were examined and photographed with a transmission electron microscope. Blood alcohol levels were also measured spectrophotometrically. RESULTS: Daily alcohol consumption of the rats was in the range of 12.09-15.50 g/kg. Blood alcohol concentrations were 145.63 mg/dl on the 21st day of alcohol consumption. Chronic alcohol consumption caused some marked aortic wall injuries. Perindopril, atenolol, and amlodipine at high doses, but not low doses, produced some significant beneficial effects on alcohol-induced aortic wall damage. CONCLUSIONS: These results imply that perindopril, atenolol, and amlodipine may have protective effects on heavy chronic alcohol consumption-induced aortic wall injury in rats only in high doses.     

Dissecting the role of hyperthermia in natural killer cell mediated anti-tumor responses.

The effects of hyperthermia on natural killer (NK) cell cytotoxicity against tumor cell targets are not yet fully understood. A more complete understanding of these effects could be important for maximizing the clinical benefits obtained by using hyperthermia for cancer therapy. Here, we summarize results in the literature regarding the effects of elevated temperatures on NK cells and our own recent data on the effects of fever-range temperatures. At treatment temperatures above 40 degrees C, (which is above the physiological body temperatures normally achieved during fever or exercise), both enhancing and inhibitory effects on cytotoxic activity of NK cells against tumor cells have been reported. Our own results have shown that fever-range thermal stress (using a temperature of 39.5 degrees C) enhances human NK cell cytotoxicity against tumor target cells. This effect requires function of the NKG2D receptor of NK cells, and is maximal when both NK and tumor cell targets are heated. Reported heat sensitive cellular targets affected by hyperthermia on tumor cells include heat shock proteins, MICA and MHC Class I. In NK cells, plasma membrane reorganization may occur after mild heat stress. We conclude this review by listing several unresolved questions that should be addressed for a more complete understanding of the molecular mechanisms which underlie the effects of thermal stress on the function of NK cells. Altogether, the available data indicate a strong potential for heat-induced enhancement of NK cell activity in mediating, at least in part, the improved clinical responses seen when hyperthermia is used in combination with other therapies.     

The prevention of myocardial ultrastructural changes by perindopril, atenolol and amlodipine in chronic alcohol administered rats.

The effects of perindopril, an angiotensin converting enzyme inhibitor, atenolol, a beta adrenergic receptor blocker and amlodipine, a calcium channel blocker were investigated in chronic alcohol administered rats. Adult male Wistar rats (240-320 g) were used in the present study. Alcohol was given to rats by a modified liquid diet for 21 days. Perindopril (2.5 and 5 mgkg(-1)), atenolol (5 and 10 mg kg(-1)) and amlodipine (5 and 10 mg kg(-1)) were injected to rats in different groups intraperitoneally for 21 days. Control rats were pair fed by an isocaloric liquid diet containing sucrose as a caloric substitute for alcohol. Saline was injected to control rats for 21 days. Rats were anesthetized with ether. Their hearts were removed and 1 mm3 samples from left ventricles were fixed. Five fields per heart were examined and photographed with transmission electron microscope. Blood alcohol levels were also measured spectrophotometrically. Daily alcohol consumption of the rats was in a range of 12.09-15.5 g kg(-1). Blood alcohol concentrations were found as 145.63 mg dl(-1) at 21st day of alcohol consumption. Chronic alcohol consumption caused some marked myocardial injuries. Perindopril and atenolol but not amlodipine produced some significant beneficial effects on alcohol-induced myocardial damages. Our results imply that perindopril and atenolol but not amlodipine have protective effects on heavy chronic alcohol consumption-induced myocardial injury in rats.     

Diagnostic radiation and the risk of multiple myeloma (United States)

Objective: To evaluate the relationship between cumulative lifetime exposure to diagnostic radiation and the risk of multiple myeloma using data from a large, multi-center, population-based case–control study. Methods: Study subjects included a total of 540 cases with newly diagnosed multiple myeloma and 1998 frequency-matched population controls living in three areas of the United States (Georgia, Michigan, New Jersey). Information on exposure to diagnostic X-rays was obtained by personal interview. Results: No association was found between case–control status and the total number of reported diagnostic X-rays of any type (odds ratio (OR) for 20 or more compared to less than 5 X-rays = 0.9, 95% confidence interval (95% CI) = 0.7–1.2). There was no evidence of an excess risk of multiple myeloma among individuals who reported exposure to 10 or more diagnostic X-rays that impart a relatively high radiation dose to the bone marrow, as compared to individuals reporting no such exposures (OR 0.7, 95% CI 0.4–1.3). Conclusions: These data suggest that exposure to diagnostic X-rays has a negligible impact, if any, on risk of developing multiple myeloma.     

PTL401, a New Formulation Based on Pro-Nano Dispersion Technology,Improves Oral Cannabinoids Bioavailability in Healthy Volunteers

There is a growing clinical interest in developing and commercializing pharmaceutical-grade cannabinoid products, containing primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). The oral bioavailability of THC and CBD is very low due to extensive “first-pass” metabolism. A novel oral THC and CBD formulation, PTL401, utilizing an advanced self-emulsifying oral drug delivery system, was designed to circumvent the “first-pass” effect. In this study, the bioavailability of THC and CBD from the PTL401 capsule was compared with similar doses from a marketed reference oromucosal spray (Sativex^®). Fourteen healthy male volunteers received, on separate treatment days, either a single dose of PTL401 or an equivalent dose of the oromucosal spray. Blood samples for pharmacokinetic analyses were collected, and safety and tolerability were assessed. PTL401 yielded 1.6-fold higher plasma C_max than the equivalent dose of the oromucosal spray, for both THC and CBD. Their relative bioavailability was also higher (131% and 116% for CBD and THC, respectively). Values of T_max were significantly shorter for both CBD and THC (median of 1.3 h for PTL401 vs. 3.5 h for the spray). The pharmacokinetic profiles of the active 11-OH-THC metabolite followed the same pattern as THC for both routes of delivery. No outstanding safety concerns were noted following either administration. We conclude that PTL401 is a safe and effective delivery platform for both CBD and THC. The relatively faster absorption and improved bioavailability, compared to the oromucosal spray, justifies further, larger scale clinical studies with this formulation.     

Sleep Disturbances and Sensory Sensitivities Co-Vary in a Longitudinal Manner in Pre-School Children with Autism Spectrum Disorders

Journal of Autism and Developmental Disorders - Previous research has demonstrated that sleep disturbances are positively correlated with sensory sensitivities in children with ASD. Most of these...     

Evaluation of eryptosis in patients with chronic kidney disease

International Urology and Nephrology - Anemia in patients with chronic kidney disease (CKD) is the result of reduced erythropoietin, disturbed erythropoiesis and decreased lifespan of circulating...