Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl ester

Cystinosis is a systemic genetic disease caused by a lysosomal transport deficiency accumulating cystine in most tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Studies performed in fibroblasts of cystinotic patients and in kidney cells loaded with cystine dimethyl ester (CDME) suggest that apoptosis is enhanced in this disease. Considering that oxidative stress is a known apoptosis inducer, our main objective was to investigate the effects of CDME loading on several parameters of oxidative stress in the kidney of young rats. Animals were injected twice a day with 1.6 μmol/g body weight CDME and/or 0.26 μmol/g body weight cysteamine (CSH) from the 16th to the 20th postpartum day and killed after 1 or 12 h. CDME induced lipoperoxidation and protein carbonylation and stimulated superoxide dismutase, glutathione peroxidase (GPx), and catalase activities, probably through the formation of superoxide anions, hydrogen peroxide, and hydroxyl free radicals. Coadministration of CSH, the drug used to treat cystinotic patients, prevented, at least in part, those effects, possibly acting as a scavenger of free radicals. These results suggest that the induction of oxidative stress might be one of the mechanisms leading to tissue damage in cystinotic patients.     

Sexually transmitted disease rates and high-risk sexual behaviors in borderline personality disorder versus borderline personality disorder with substance use disorder

We examined the rates of sexually transmitted diseases (STDs) in women with borderline personality disorder (BPD) (using PDE and SCID-II) and substance abuse or dependence (SCID-I) (BPD-SUD) (N=82) compared with those with BPD-only (N=102), exploring mediators of this relationship. Participants were interviewed about STD history (gonorrhea, genital herpes, syphilis, trichomonas, human papillomavirus, and HIV), condom use, number of sexual partners, poverty, and prostitution. BPD-SUD appeared to be particularly at high risk for STDs, reporting significantly more STDs than BPD (F[1,172]=11.74, p=0.001, d=.27), particularly for gonorrhea, trichomonas, and human papillomavirus. The relationship between BPD-SUD and STDs is mediated by poverty, prostitution in the last year, recent unprotected sex with two or more partners, and >20 lifetime partners (z=-2.16 which is p=0.03), with prostitution alone making a significant contribution to this relationship (z=-2.49, p=0.01).     

Toxicity and metabolism of p-chlorophenol in the marine microalga Tetraselmis marina

Toxicity and metabolism of para-chlorophenol (p-CP) in the marine microalga Tetraselmis marina have been studied. The inhibition constant EC(50) for p-CP was 272+/-17 microM (34.8+/-2.2 mg L(-1)) under the experimental conditions. Two metabolites were detected in the growth medium in the presence of p-CP by reverse phase HPLC and their concentrations increased at the expense of p-CP. The two metabolites, which were found to be more polar than p-CP, were isolated by a C18 column. They were identified as p-chlorophenyl-beta-D-glucopyranoside (p-CPG) and p-chlorophenyl-beta-D-(6-O-malonyl)-glucopyranoside (p-CPGM) by electrospray ionization-mass spectrometric analysis in a negative ion mode. The molecular structures of p-CPG and p-CPGM were further confirmed by enzymatic and alkaline hydrolyses. Treatment with beta-glucosidase released free p-CP and glucose from p-CPG, whereas p-CPGM was completely resistant. Alkaline hydrolysis completely cleaved the esteric bond of the malonylated glucoconjugate and yielded p-CPG and malonic acid. It was concluded that the pathway of p-CP metabolism in T. marina involves an initial conjugation of p-CP to glucose to form p-chlorophenyl-beta-d-glucopyranoside, followed by acylation of the glucoconjugate to form p-chlorophenyl-beta-D-(6-O-malonyl)-glucopyranoside. The metabolism of p-CP in T. marina was mainly driven by photosynthesis, and to a lesser extent by anabolic metabolism in the dark. Accordingly, the detoxification rate under light was about seven times higher than in the darkness. This work provides the first evidence that microalgae can adopt a combined glucosyl transfer and malonyl transfer process as a survival strategy for detoxification of such xenobiotics as p-CP.     

A pharmacophore derived phenytoin analogue with increased affinity for slow inactivated sodium channels exhibits a desired anticonvulsant profile

Phenytoin (DPH) is a clinically useful sodium (Na) channel blocker with efficacy against partial and generalized seizures. We have developed a novel hydantoin compound (HA) using comparative molecular field analysis (CoMFA) and evaluated its effects on hNa(v)1.2 channels. Both DPH and HA demonstrated affinity for resting (K(r)=13.9microM for HA, K(r)=464microM for DPH) and slow inactivated channels (K(I)=975nM for HA, K(I)=20.6microM for DPH). However, HA also exhibited an affinity for fast inactivated channels (K(I)=2.5microM) and shifted the V(1/2) for activation in the depolarizing direction. Furthermore, HA exhibited profound use dependent block at both 5 and 10Hz stimulation frequencies. In the 6Hz seizure model (32mA) HA had an ED(50) of 47.1mg/kg and a TD(50) of 131mg/kg (protective index (PI)=2.8). In comparison, the ED(50) for DPH was approximately 27.5mg/kg with a TD(50) of 35.6mg/kg (PI approximately 1.3). These findings provide evidence for the utility of CoMFA in the design of novel anticonvulsants and support the hypothesis that states selectivity plays an important role in achieving optimal protection with minimal side effects.     

Laboratory and field studies of naps and caffeine as practical countermeasures for sleep-wake problems associated with night work

STUDY OBJECTIVES: To evaluate the effects of napping, caffeine, and napping plus caffeine on performance and alertness in both laboratory and field settings. DESIGN: (1) Laboratory Study: parallel-groups design with random assignment to 1 of 4 experimental conditions. (2) Field Study: crossover design. SETTING: Sleep laboratory and field settings. PARTICIPANTS: (1) Laboratory Study: 68 healthy individuals; (2) Field Study: 53 shiftworkers who worked nights or rotating shifts. INTERVENTIONS: (1) Laboratory Study: an evening nap opportunity before the first 2 of 4 consecutive simulated night shifts plus placebo taken all 4 nights, caffeine taken nightly, the combination of the nap and caffeine conditions, or placebo. (2) Field Study: an evening nap on the first 2 of 4 consecutive night shifts plus caffeine taken nightly versus placebo taken nightly without naps. MEASUREMENTS AND RESULTS: (1) Laboratory Study: Napping, caffeine, and their combination all improved alertness and performance as measured by Maintenance of Wakefulness Test and Psychomotor Vigilance Task, but the combination of napping and caffeine was best in improving alertness. (2) Field Study: Napping plus caffeine improved performance as measured by Psychomotor Vigilance Test and decreased subjective sleepiness in individuals working the night shift. CONCLUSIONS: Napping plus caffeine helps improve performance and alertness of night-shift workers.     

Patient receptivity to tobacco cessation counseling in an academic dental clinic: a patient survey

OBJECTIVE: This study investigated dental patient attitudes towards tobacco cessation counseling in the dental school setting. METHODS: Patients attending an academic dental clinic during a six-week period were asked to complete a 22-item self-administered survey. Means and frequency distributions were assessed on all variables as appropriate. RESULTS: Response rate was 71%. Twenty-nine percent of respondents reported that they currently used tobacco. Seventy-two percent of tobacco users agreed that the student dentist should ask patients whether or not they use tobacco, 67% agreed that the student dentist should advise tobacco users to quit, and 89% agreed that student dentists should offer quit tobacco information to patients who want to quit. Seventy percent of tobacco users were considering quitting or currently trying to quit. Of these, only 31% were aware of community resources to help them quit. CONCLUSIONS: The majority of tobacco users were positive in their attitudes toward delivery of tobacco cessation counseling and services in the dental setting. Many were considering or trying to quit, but few were aware of community resources to help them.