Preliminary evidence for normalization of risk taking by modafinil in chronic cocaine users

Modafinil, a wake-promoting agent used to treat sleep disorders, is thought to enhance cognition. Although modafinil has shown promise as a pharmacotherapy for the treatment of cocaine dependence, it is unknown to what extent cognitive effects may play a role in such treatment. We examined the effect of modafinil on the Balloon Analogue Risk Task (BART), a behavioral measure in which higher scores are purported to reflect a greater propensity for risk-taking. Thirty cocaine dependent individuals, enrolled in a randomized clinical trial of modafinil 400 mg (n = 12) versus placebo (n = 18), were administered the BART during the second week of inpatient treatment for cocaine dependence. A comparison cohort of healthy participants (n = 19) performed the BART under similar conditions. Modafinil treatment was associated with significantly higher BART scores (p = 0.01), which were comparable to scores in healthy persons. BART scores in placebo treated participants were much lower than previously reported in healthy participants, and lower than those observed in the comparison cohort. As propensity toward risk taking is typically associated with higher BART scores as well as increased risk for substance use, our findings may reflect a novel aspect of cognitive impairment related to chronic cocaine use. Notably, the low BART scores reflect highly suboptimal performance on the task, and the observed effect of modafinil may indicate a normalization of this impairment and have implications for treatment outcome.     

Microbiological aspects of vulvovaginitis in prepubertal girls

This study aimed to establish the vaginal introitus microbial flora in girls with and without symptoms of vulvovaginitis, and to present the distribution of isolated microorganisms by age groups in girls with vulvovaginitis. We enrolled 500 girls with vulvovaginitis symptoms, aged 2-12 years, referred by their pediatricians for microbiological examination of the vaginal introitus swabs, and 30 age-matched asymptomatic girls. Similar microbial flora was isolated in both groups, but the symptomatic girls had significantly more common positive microbiological findings compared to controls (p?相似文献   

Different responses of Drosophila subobscura isofemale lines to extremely low frequency magnetic field (50 Hz, 0.5 mT): fitness components and locomotor activity

Purpose: Extremely low frequency (ELF) magnetic fields as essential ecological factors may induce specific responses in genetically different lines. The object of this study was to investigate the impact of the ELF magnetic field on fitness components and locomotor activity of five Drosophila subobscura isofemale (IF) lines.

Materials and methods: Each D. subobscura IF line, arbitrarily named: B16/1, B24/4, B39/1, B57/2 and B69/5, was maintained in five full-sib inbreeding generations. Their genetic structures were defined based on the mitochondrial DNA variability. Egg-first instar larvae and 1-day-old flies were exposed to an ELF magnetic field (50?Hz, 0.5?mT, 48?h) and thereafter, fitness components and locomotor activity of males and females in an open field test were observed for each selected IF line, respectively.

Results: Exposure of egg-first instar larvae to an ELF magnetic field shortened developmental time, and did not affect the viability and sex ratio of D. subobscura IF lines. Exposure of 1-day-old males and females IF lines B16/1 and B24/4 to an ELF magnetic field significantly decreased their locomotor activity and this effect lasted longer in females than males.

Conclusions: These results indicate various responses of D. subobscura IF lines to the applied ELF magnetic field depending on their genetic background.     

Diagnostic validity of ICDAS and DIAGNOdent combined: an in vitro study in pre-cavitated lesions

In a continuous process such as caries, it is important to possess criteria or instruments that allow the lesions to be diagnosed at early stages so that preventive or interceptive treatments can be applied before cavitation takes place. The present study seeks to assess the diagnostic efficacy of the International Caries Detection and Assessment System (ICDAS II) criteria and the DIAGNOdent laser fluorescence (LF) pen in occlusal caries lesions, using histological sections as the gold standard. Sixty-four permanent teeth were examined by two researchers who previously performed and calibrated both the ICDAS II criteria and the use of DIAGNOdent pen. The teeth were then cut into sections and observed under an optical microscope. The sensitivity values were 0.82 (ICDAS II) and 0.85 (LF). The specificity values were 1.00 (ICDAS II) and 0.53 (LF). The intraexaminer reproducibility was 0.892 for ICDAS II and 0.912 for the DIAGNOdent, so it was high for both diagnostic methods. However, the DIAGNOdent pen showed greater sensitivity and the ICDAS criteria more specificity. It was concluded that both methods are efficacious individually but combining the two is recommended to improve the diagnosis.     

High glucose regulates the activity of cardiac sarcolemmal ATP-sensitive K+ channels via 1,3-bisphosphoglycerate: a novel link between cardiac membrane excitability and glucose metabolism

Because we were interested in assessing glucose-mediated regulation of the activity of sarcolemmal ATP-sensitive K(+) channels (K(ATP) channels) (which are closed by physiological levels of intracellular ATP and serve to couple intracellular metabolism with the membrane excitability in the heart) during ischemia, we performed experiments designed to test whether high extracellular glucose would have effects on sarcolemmal K(ATP) channels per se. Surprisingly, we found that high extracellular glucose (50 mmol/l) activates sarcolemmal K(ATP) channels in isolated guinea pig cardiomyocytes. To activate K(ATP) channels, glucose had to be transported into cardiomyocytes and subjected to glycolysis. The activation of these channels was independent of ATP production and intracellular ATP levels. The effect of glucose on sarcolemmal K(ATP) channels was mediated by the catalytic activity of glyceraldehyde-3-phosphate dehydrogenase and consequent generation of 1,3-bisphosphoglycerate. The 1,3-bisphosphoglycerate (20 mmol/l), an intermediate product of glycolysis, directly targeted and activated K(ATP) channels, despite physiological levels of intracellular ATP (5 mmol/l). We conclude that glucose, so far exclusively viewed as a metabolic fuel in the heart important only during ischemia/hypoxia, may serve a signaling role in the nonstressed myocardium by producing an agent that regulates cardiac membrane excitability independently of high-energy phosphates.     

Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats

Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA–DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA–DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5?mg/kg), HPMA–DOX (5?mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA–DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer–drug conjugate and other nano-sized-drug constructs.     

Can the Vaginal Photoplethysmograph and Its Associated Methodology Be Used to Assess Anal Vasocongestion in Women and Men?

Archives of Sexual Behavior - Forty years ago, researchers documented changes in vascular and muscular activity within the anal canal of women and men who engaged in sexual self-stimulation....