Thiodiglycolic acid: a major metabolite of bis(2-chloroethyl)ether.

Male rats were given a single oral dose (40 mg/kg) of bis(2-chloroethyl)ether (BCEE). Less than 2% of the dose was recovered from the expired air as the unaltered parent compound during an 8-hr collection period. Urine samples representing 48 hr of collection were analyzed by gas chromatography-mass spectrometry. Methyl ester/trimethylsilyl ether derivatives of the isolated urinary acid fraction were prepared for gas-phase analysis. Two metabolites were identified in this fraction: thiodiglycolic acid (TDGA) and 2-chloroethyl β-d-glucosiduronic acid. Quantitative analysis for TDGA gave an average (seven rats) yield for 48 hr of 33 ± 11.8 mg (± SD) of TDGA/kg from a single dose of 40 mg/kg BCEE. The glucuronide of 2-chloroethanol was synthesized using rabbit liver microsomes in an incubation mixture. The matching mass spectrum of the glucuronide prepared in vitro to that identified in the urine of the rats verified 2-chloroethyl β-d-glucosiduronic acid as a metabolite of BCEE.     

The effects of eticlopride on Morris water task performance in male and female rats neonatally treated with quinpirole

Rationale Previous studies have shown that neonatal quinpirole treatment which results in long-term dopamine D2 receptor supersensitization (D2 receptor priming) produces cognitive deficits in preweanling and adult rats behaviorally tested on the Morris water task (MWT).Objective This study was designed to analyze whether pretraining administration of the D2 antagonist eticlopride alleviates cognitive deficits produced by neonatal quinpirole treatment.Methods Both male and female Sprague–Dawley rats were treated with quinpirole HCl (1 mg/kg) or saline from postnatal days 1 to 21. From P22 to P24, rats were tested on the place version of the MWT in which a hidden platform remains stationary throughout training. From P25 to P28, rats were tested on the match-to-place version of the MWT, and rats are given a pair of daily training trials to locate the hidden platform that was moved to a new location each day. Fifteen minutes before each training session, rats were intraperitoneally administered with eticlopride (0.01 or 0.02 mg/kg) or saline.Results Pretraining eticlopride treatment alleviated cognitive deficits produced by neonatal quinpirole treatment in both male and female rats on the place version of the MWT, as well as in males tested on the match-to-place version of the MWT. However, there were no significant deficits produced by neonatal quinpirole treatment in females tested on the match-to-place version of the MWT, and control males demonstrated superiority over control females on this version of the task.Conclusions Pretraining administration of the dopamine D2 antagonist eticlopride alleviated cognitive deficits produced by neonatal quinpirole treatment. However, it appears that the dopamine D2 receptor may have a more important influence on cognitive performance in males than in females, which may be related to increased sensitivity of the D2 receptor in males.     

The role of social norms and friends' influences on unhealthy weight-control behaviors among adolescent girls

Dieting is common among adolescent girls and may place them at risk of using unhealthy weight-control behaviors (UWCBs), such as self-induced vomiting, laxatives, diet pills, or fasting. Research has suggested that social factors, including friends and broader cultural norms, may be associated with UWCBs. The present study examines the relationship between the school-wide prevalence of current weight loss efforts among adolescent girls, friends' dieting behavior, and UWCBs, and investigates differences in these associations across weight categories. Survey data were collected in 31 middle and high schools in ethnically and socio-economically diverse communities in Minnesota, USA. The response rate was 81.5%. Rates of UWCBs were compared across the spectrum of prevalence of trying to lose weight and friends' involvement with dieting, using chi(2) analysis and multivariate logistic regression, controlling for demographic factors and clustering by school. Girls with higher body mass index (BMI) were more likely to engage in UWCBs than those of lower BMI. Multivariate models indicated that friends' dieting behavior was significantly associated with UWCBs for average weight girls (OR = 1.57, CI = 1.40-1.77) and moderately overweight girls (OR = 1.47, CI = 1.19-1.82). The school-wide prevalence of trying to lose weight was significantly, albeit modestly, related to UWCBs for average weight girls (15th-85th percentile; OR = 1.17, CI = 1.01-1.36), and marginally associated for modestly overweight girls (85th-95th percentile; OR = 1.21, CI = .97-1.50), even after controlling for friends' dieting behaviors. The social influences examined here were not associated with UWCBs among underweight ( < 15th percentile) or overweight ( > 95th percentile) girls. Findings suggest that social norms, particularly from within one's peer group, but also at the larger school level may influence UWCBs, particularly for average weight girls. Implications for school-based interventions to reduce UWCBs are discussed.     

Bilateral bispectral index monitoring during suppression of unilateral hemispheric function

Bispectral Index (BIS) has been used to monitor level of "sedation" based on the electroencephalogram (EEG). Patients evaluated for surgery to control a seizure disorder undergo Wada testing, during which one hemisphere is rendered functionally inactive after injecting a short-acting barbiturate. We surmised that the BIS values would reflect these functional changes. Eight epileptic patients were enrolled. A full array of 21 EEG electrodes and 2 BIS XP (Quatro) strips over each frontal region of the scalp were applied. The EEG was continuously recorded. BIS values from each hemisphere were recorded every minute. Angiography was performed by advancing a catheter into each internal carotid artery. Amobarbital or methohexital was injected until the patient developed a hemiparesis. The EEG confirmed a significant lateralized cortical effect of the barbiturate. Repeated measures analysis of variance was used to analyze the differences between the BIS values from monitor electrode strips placed on the left (left BIS) and the right (right BIS) sides of the head as well as the differences in the left and right BIS values before and after each injection of the barbiturate. Injection of barbiturate into either the left or right internal carotid artery produced a significant change on the 21-electrode EEG. However, there was no difference between left BIS to right BIS values (P = 0.84). With repeated injections of barbiturates, some patients became sedated. At these times, both left BIS and right BIS values decreased together before and after injection of barbiturate. The BIS monitor was unable to distinguish significant hemispheric EEG and clinical functional changes except when the patient became sedated.     

The multiple feedback loop hypothesis of chronic diseases

The body uses multiple feedback loops to regulate the storage and retrieval of critical substances to maintain homeostasis. In the presence of a deficiency of some required constituents, this system will extract the required constituent from tissue storage. If this deficiency persists, after an extended period of time, the extraction depletes the stores of a constituent in the cells rendering the various cellular pumps ineffective in further extraction. When this happens, the endocrine system releases hormones instructing the immune system to assist in the extraction process. This results in inflammation and cumulative cellular damage. When there is a large quantity of tissue available the individual cellular damage will be less severe, but the total cumulative effect can still be significant to the point of being incapacitating. This cumulative cellular damage is the chronic disease like arthritis. Because of limited quantities of a tissue type, like myelin, the cumulative cellular damage can progress to such an extent that the immune system can no longer recognize the individual cells, which initiates an immune system response.     

The relation between subjective and objective measures of everyday life activities in persons with multiple sclerosis

OBJECTIVES: To investigate the relation between subjective and objective performance-based measures of functional status in persons with multiple sclerosis (MS), and to compare their performance with healthy controls. DESIGN: A between-groups design, using a correlational approach to examine the relation between objective and subjective measures of functional capacity. SETTING: Outpatient rehabilitation research institution. PARTICIPANTS: Seventy-four subjects with clinically definite MS and 35 healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Executive Function Performance Test (EFPT), Functional Assessment of Multiple Sclerosis (FAMS), and Functional Behavior Profile (FBP). RESULTS: MS participants reported more difficulties performing functional tasks than did the healthy controls. MS participants also performed significantly worse on the EFPT than healthy controls. However, all correlations between subjective and objective functional measures were nonsignificant. After controlling for depressive symptomatology, EFPT performance was significantly associated with FBP scores, but not FAMS scores. CONCLUSIONS: The lack of association between objective performance-based measures and subjective self-report measures of functional activities is a challenge to outcomes measurement and has implications for assessment of functional performance. Results are discussed in terms of the different dimensions that these tools are measuring and their respective strengths and limitations.