3H-nicotine, 3H-flunitrazepam, and 3H-cocaine incorporation into melanin: a model for the examination of drug-melanin interactions

To explore drug-melanin interactions, we examined the in vitro tyrosinase-mediated formation of melanin from tyrosine in the presence of the 3H-cocaine (3H-COC), 3H-flunitrazepam (3H-FLU), and 3H-nicotine (3H-NIC) at 10-100,000 ng/mL. Polymerization in the presence of 10 or 100 ng/mL of each drug resulted in almost complete drug incorporation into the melanin pellet. Only 12% (3H-NIC) to 28% (3H-FLU) of the pellet-associated radioactivity could be released upon treatment with 6 M HCl. At 1000-100,000 ng/mL, between 20 and 50% of label became melanin-associated. In each case a significant percentage of melanin-associated radioactivity was resistant to treatment with 6 M HCl. Nicotine-associated radioactivity in the polymer was subject to much greater quenching than was 3H-COC or 3H-FLU, suggesting a much tighter association with the melanin. The subsequent demonstration of a covalent adduct of a melanin intermediate and nicotine has demonstrated the utility of this polymerization system as a model for further chemical characterization of drug-melanin interactions.     

Increased corticotropin-releasing factor concentrations in the bed nucleus of the stria terminalis of anhedonic rats

Chronic mild stress in rats is an antidepressant-responsive model for anhedonic symptoms of major depression. Many patients with depression exhibit alterations in hypothalamic-pituitary-adrenal axis activity, and corticotropin-releasing factor (CRF) neuronal function. This study investigated the potential involvement of CRF and CRF receptors in the development of chronic mild stress-induced anhedonia in rats. Rats were subjected to 19 days of chronic mild stress, during which time anhedonia was periodically assessed by determining the threshold for self-stimulation of the ventral tegmental area. Anhedonic rats exhibited a 50% increase in CRF concentrations in the bed nucleus of the stria terminalis compared to control rats. There were no significant changes in hypothalamic-pituitary-adrenal axis activity, CRF or CRF(1) receptor mRNA expression, or CRF receptor binding in the brain regions analyzed. Though preliminary, these results are consistent with the hypothesis that chronic stress-induced modulation of CRF function in specific brain structures such as the bed nucleus of the stria terminalis may contribute to the pathophysiology of depression.     

Surgical versus non-surgical endodontic re-treatment for periradicular lesions

Background : Though success rates of endodontic initial treatment have been improving over the years, persistence of periapical disease is far from being a rare condition. The most common therapeutical options for the re‐treatment of teeth with periapical pathosis are non‐surgical orthograde treatment and surgical treatment. Selection between alternative treatments should be based on assessment of respective benefits (mainly healing) and risks from studies consistent with a high level of evidence. Objectives : To test the null hypothesis of no difference in outcome between surgical and non‐surgical therapy for endodontic re‐treatment of periradicular lesions. Search strategy : The Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE were searched with appropriate search strategies. Handsearching included eight dental journals. The bibliographies of relevant clinical trials and relevant articles were checked for identifying studies outside the handsearched journals. Seven manufacturers of instruments in the field of endodontics or endodontic surgery or both, as well as the authors of the identified randomized controlled trials (RCTs) were contacted in order to identify unpublished or ongoing RCTs. No language restriction was placed. The last electronic search was conducted on 3rd April 2007. Selection criteria : All RCTs about re‐treatment of teeth with periapical pathosis in which both surgical and non‐surgical approaches were used and having a follow up of at least 1 year were considered for the analysis. Data collection and analysis : A quality assessment of the included RCTs was carried out and the authors were contacted for missing information. We independently extracted the data in duplicate. We followed the Cochrane Oral Health Group's statistical guidelines. Main results : Three RCTs were identified, two of them reporting different data from the same clinical study. The risk of bias was judged as moderate for one study and high for the other one. One hundred and twenty‐six cases were followed up for at least 1 year, and 82 had a follow up of 4 years. At the 1‐year follow up the success rate for surgical treatment was slightly better than non‐surgical (risk ratio (RR) 1.13; 95% confidence interval (CI) 0.98 to 1.30). When the follow up was extended to 4 years (only one RCT made it) the outcome for the two procedures became similar. Authors' conclusions : The finding that healing rates can be higher for cases treated surgically as compared to those treated non‐surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re‐treatment of a periradicular pathosis. More well‐designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.     

Common bile duct stones: reassessment of criteria for CT diagnosis

To evaluate the specificity of previously suggested computed tomographic (CT) criteria for diagnosing common bile duct (CBD) stones, CT scans of 38 patients with CBD stones were compared with scans of 32 patients with carcinoma obstructing the CBD and 28 nonobstructed patients. The CBD stone was directly visualized as a target sign or densely calcified structure in 29 of 38 patients with stones (76%); one with carcinoma showed a similar target sign. A rim of increased density in the distal CBD was found without accompanying target sign in six patients with stones (16%), compared with 12 with carcinoma (38%) and 15 nonobstructed patients (54%). Irregular intraluminal densities without a detectable target sign were noted in four patients with stones (11%), compared with eight with carcinoma (25%) and nine nonobstructed patients (32%). Abrupt termination of the CBD without a mass was more common as an isolated finding in patients with carcinoma (31%) than in patients with stones (13%). CT is accurate in detecting CBD stones in certain patient populations, but direct visualization of the stone is required.     

Inhibition of excitatory neurotransmission with kynurenate reduces brain edema in neonatal anoxia

Excitatory amino acid neurotransmitters have been implicated in fostering brain edema and neuronal death in ischemia. As both of these processes are involved in nervous system damage during neonatal anoxia, the effect of blockade of cell excitation with kynurenate upon brain water was studied following anoxic-ischemic brain injury in neonatal rats. Such treatment attenuated brain edema immediately after, and 24 h following anoxia-ischemia.     

Short-term diagnostic stability of schizotypal,borderline, avoidant,and obsessive-compulsive personality disorders

OBJECTIVE: Personality disorders are defined as enduring patterns of maladaptive behaviors and traits that are stable over time. This study prospectively examined the stability of four personality disorders (schizotypal, borderline, avoidant, and obsessive-compulsive) over a 1-year follow-up period. METHOD: Subjects (N=668) were recruited from multiple clinical settings at four collaborating institutions. Subjects met criteria for one or more of the four personality disorders or were part of a comparison group of subjects with major depressive disorder and no personality disorder. Diagnoses were established by using semistructured interviews. Follow-up assessments, conducted 6 and 12 months after the baseline assessment, included monthly ratings of all criteria for the four personality disorders and weekly ratings of the course of major depressive disorder. The current report is based on 621 subjects with complete data through 12 months of the follow-up period. RESULTS: Significantly more subjects in each personality disorder group remained at diagnostic threshold throughout the 12 months of the follow-up period than did those in the major depressive disorder group. A continuous measure of number of criteria met was highly correlated across the three assessments. The majority of personality disorder subjects, however, did not consistently remain at diagnostic threshold, and the mean number of criteria met decreased significantly for each group. CONCLUSIONS: Individual differences in personality disorder features appear to be highly stable, although the number of criteria present decreases over time. Personality disorders may be characterized by stable trait constellations that fluctuate in degree of maladaptive expression.     

Long-term course of pediatric obsessive–compulsive disorder: 3 years of prospective follow-up

Objective

This study assesses the long-term course of treatment-seeking youth with a primary diagnosis of DSM-IV OCD.

Method

Sixty youth and their parents completed intake interviews and annual follow-up interviews for 3 years using the youth version of the Longitudinal Interval Follow-up Evaluation (Y-LIFE) and Children's Yale–Brown Obsessive Compulsive Scale (CY-BOCS). Remission was defined as no longer meeting DSM-IV criteria for OCD for 8 weeks or more, and recurrence was defined as meeting full criteria for OCD for 4 consecutive weeks after having achieved symptom remission. Remission rates for youth were compared to rates of adults participating in the same study.

Results

The probability of achieving partial remission of OCD was 0.53 and the probability of achieving full remission was 0.27. Among the 24 youth participants who achieved remission, 79% stayed in remission throughout the study (mean of 88 weeks of follow-up) and 21% experienced a recurrence of symptoms. Better functioning at intake and a shorter latency to initial OCD treatment were associated with faster onset of remission (P < .001).

Conclusions

Remission is more likely among youth versus adults with OCD. Treatment early in the course of illness and before substantial impact on functioning predicted a better course.     

Work factors facilitating working beyond state pension age: Prospective cohort study with register follow-up

Objectives:The demographic changes in Europe underline the need for an extension of working lives. This study investigates the importance of physical work demands and psychosocial work factors for working beyond the state pension age (65 years).Methods:We combined data from three cohorts of the general working population in Denmark (DWECS 2005 and 2010, and DANES 2008), where actively employed workers aged 55–59 years replied to questionnaires about work environment and were followed until the age of 66 years in the Danish AMRun register of paid employment. Using logistic regression analyses, we calculated prevalence ratios (PR) and 95% confidence intervals (CI) for the association between physical and psychosocial work factors and working beyond state pension age, adjusted for age, sex, cohort, cohabiting, sector, income, vocational education, working hours, lifestyle, and previous sickness absence.Results:Of the 2884 workers aged 55–59 years, 1023 (35.5%) worked beyond the state pension age. Higher physical work demands was associated with a lower likelihood (PR 0.69, 95% CI 0.58–0.82) and a good psychosocial work environment was associated with higher likelihood (average of 7 items: PR 1.81, 95% CI 1.49–2.20) of working beyond state pension age. Stratified analyses did not change the overall pattern, ie, a good overall psychosocial work environment – as well as several specific psychosocial factors – increased the likelihood of working beyond state pension age, both for those with physically active and seated work.Conclusion:While high physical work demands was a barrier, a good psychosocial work environment seems to facilitate working beyond state pension age, also for those with physically active work.