Biochemical evidence of the functional recovery and regeneration of adrenal autotransplants in the rat spleen

Adrenal transplantation may restore adrenal function after bilateral adrenalectomy or when adrenal function is lost. Thus, animal experiments could provide useful information before clinical application of adrenal transplantation. Using an experimental model of autotransplantion of a complete adrenal gland in the spleen of adrenalectomized rats, several biochemical and hormonal parameters were studied to evaluate the function of transplanted adrenal tissue compared to control and adrenalectomized animals. Three weeks after surgery, the animals were sacrificed and plasma and tissue samples were obtained for biochemical studies. In the autotransplanted rats, plasma glucose, hepatic glycogen, plasma, and hepatic proteins, which were decreased in adrenalectomized rats, increased to values close to those of the control group; whereas muscle and thymus proteins, which were increased in adrenalectomized animals, decreased and reached normal levels. Corticosterone plasma levels in autotransplanted rats showed a 50% recovery compared to control animals, whereas plasma aldosterone concentrations were low, with similar values to those of the adrenalectomized group. These results provide evidence that the adrenal grafts secrete corticosterone in quantities enough to overcome hepatic inactivation. On the other hand, aldosterone plasma concentrations remain very low, plasma potassium levels are increased, and plasma sodium levels are decreased in animals with intrasplenic adrenal grafts, indicating that aldosterone production is insufficient to avoid hypoaldosteronism.     

Effects of injecting thymulin into the anterior or medial hypothalamus or the pituitary on induced ovulation in prepubertal mice

In prepubertal mice, subcutaneous thymulin injection before equine chorionic gonadotrophin (eCG) treatment simulates ovulation; seemingly, the thymulin could be acting at the hypothalamus-pituitary axis level. OBJECTIVE: This study was designed to analyze the effects of injecting thymulin into the hypothalamus or pituitary on induced ovulation of prepubertal mice. METHOD: Female mice, 19 days old, were anesthetized with ether and injected with saline solution or thymulin into the anterior or medial hypothalamus or the pituitary and treated with eCG when 20 days old. The ova shed were counted and serum concentrations of 17beta-estradiol were measured. In the ovaries, the morphometrical analysis was performed and the atresia evaluated. RESULTS: Ether anesthesia treatment blocked eCG-induced ovulation in almost all animals. Mice anesthetized and treated with eCG and gonadotrophin-releasing hormone (GnRH) or human chorionic gonadotrophin (hCG) ovulated a full quota of ova. Injecting saline solution into the anterior or medial hypothalamus or the pituitary did not reduce the blocking effects of ether anesthesia on induced ovulation, but the incidence of atretic follicles was higher. Injecting thymulin directly into the anterior hypothalamus did not restore ovulation, nor diminish the number of atretic follicles. In contrast, injecting thymulin into the medial hypothalamus restored the ovulation ratio and decreased the percentage of atretic follicles. Similar results were obtained by injecting thymulin into the pituitary, though thymulin treatment in the pituitary resulted in a higher number of ova shed and lower follicular atresia. CONCLUSION: The present results suggest that thymulin acts at the medial hypothalamus level, facilitating the release of GnRH and at the pituitary level regulating gonadotrophin release.     

Child anxiety in primary care: prevalent but untreated

We present prevalence and treatment utilization rates for child anxiety disorders in a university-affiliated primary care clinic. Families were recruited from a pediatric patient list and 714 families participated in an initial study wherein they completed child anxiety questionnaires. According to parent and child self-report questionnaires (n=714), 22% and 20% of children, respectively, were above a suggested clinical cutoff on a brief anxiety screen; 19% and 14% of children exceeded clinical cutoffs on a separate social anxiety questionnaire. All families were invited to participate in a second study that included the Anxiety Disorders Interview Schedule for Children-Parent Version and questions about treatment utilization; telephone interviews with 190 parents showed 1-year prevalence rates of DSM-IV child disorders to be 10.0% (se=2.2%) for specific phobia, 6.8% (se=1.8%) for social phobia, 3.2% (se=1.3%) for generalized anxiety disorder, 0.5% (se=.7%) for selective mutism, 1.6% (se=.9%) for major depressive disorder, 1.1% (se=.7%) for dysthymia, and 12.6% (se=2.4%) for attention deficit-hyperactivity disorder (ADHD). Among children with a current anxiety disorder, 31% had received counseling or medication treatment during their lifetime, compared to 40% of children with depression and 79% with ADHD. Adolescent age and being Caucasian were predictors of psychotherapy use; having an ADHD diagnosis was a predictor of both psychotherapy and medication use. The high prevalence of impairing anxiety disorders, in concert with the very low extent of treatment utilization, suggests a need for methods to identify and disseminate empirically validated treatments for these disorders in the primary care setting.     

Clinical trial: single- and multiple-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects

Background The pharmacokinetics of polyethylene glycol 3350 (PEG‐3350) have not been fully described because of lack of a sufficiently sensitive analytical method. Aim To describe the pharmacokinetics of PEG‐3350 in humans. Methods A highly sensitive, high performance liquid chromatography with mass spectrometry (HPLC/MS/MS) method was developed for PEG‐3350 in urine, plasma and faeces with quantification limits of 30 ng/mL, 100 ng/mL and 500 μg/g respectively. Noncompartmental pharmacokinetics methods were used and the effects of gender, age, renal status and dosing frequency were examined after the oral administration of 17 g to healthy volunteers. Results Peak PEG‐3350 plasma concentrations occurred at 2–4 h and declined to nonquantifiable levels usually within 18 h after single and multiple doses, with a half‐life of about 4–6 h. Steady state was reached within 5 days of dosing. Mean urinary excretion of the administered dose ranged from 0.19% to 0.25%. Age, gender or mild kidney impairment did not alter the pharmacokinetics of PEG‐3350. Mean faecal excretion of the administered dose was 93% in young subjects. Conclusions For the first time, a highly sensitive assay allowed comprehensive pharmacokinetics studies of PEG‐3350 in humans. These studies confirmed that orally administered PEG‐3350 is minimally absorbed, rapidly excreted and primarily eliminated via faeces.     

Scrutinizing the relationship between shyness and social phobia

The nature of the relationship between shyness and social phobia can be clarified by assessing rates of social phobia in highly shy and normative samples. In the present study, 2202 participants were screened and categorized on a shyness scale as highly shy (90th percentile) or "normatively" shy (40-60th percentile). The Composite International Diagnostic Interview and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II; Avoidant Personality Disorder module) were used to assign clinical diagnoses. Approximately 49% of individuals in the highly shy group had a social phobia diagnosis compared to 18% in the normatively shy group. Significantly more generalized social phobia (36% vs. 4%) and avoidant personality disorder (14% vs. 4%) diagnoses were present in the highly shy group compared to the normatively shy group. Equal rates of nongeneralized social phobia (i.e., 14% vs. 14%) were present in the highly shy and the normatively shy comparison group. Findings suggest that shyness and social phobia (especially the generalized type) are related constructs but not completely synonymous; an individual can be extremely shy yet not have a social phobia diagnosis.     

Low serum levels of dehydroepiandrosterone and cortisol in human diffuse cutaneous leishmaniasis by Leishmania mexicana

Low levels of dehydroepiandrosterone (DHEA) and cortisol hormones produced by the suprarenal cortex have been associated with diseases involving chronic inflammation, low interferon (IFN)-gamma, and high interleukin (IL)-6. Diffuse cutaneous leishmaniasis (DL), a long-lasting intracellular parasitic infectious disease, can spread unknown levels of DHEA and cortisol. Serum concentrations of both were measured in 5 patients with DL, in 15 patients with localized lesions produced by Leishmania (LL), and in 20 healthy volunteers. Leishmania mexicana mexicana was identified as the causal agent in patients with DL and LL. Hormone levels were lower in DL compared with controls and LL. Furthermore, we detected a lower percentage of IFN-gamma-positive cells with higher levels of IL-6 and higher titers of anti-Leishmania antibodies in patients with DL, whereas patients with LL were similar to controls. These data suggest that patients with DL may be good candidates for DHEA and cortisol supplementation.     

Selective Mutism Questionnaire: measurement structure and validity

ObjectiveTo evaluate the factor structure, reliability, and validity of the 17-item Selective Mutism Questionnaire (SMQ).MethodDiagnostic interviews were administered via telephone to 102 parents of children identified with selective mutism (SM) and 43 parents of children without SM from varying U.S. geographic regions. Children were between the ages of 3 and 11 inclusive and comprised 58% girls and 42% boys. SM diagnoses were determined using the Anxiety Disorders Interview Schedule for Children-Parent Version; SM severity was assessed using the 17-item SMQ; and behavioral and affective symptoms were assessed using the Child Behavior Checklist. An exploratory factor analysis was conducted to investigate the dimensionality of the SMQ and a modified parallel analysis procedure was used to confirm exploratory factor analysis results. Internal consistency, construct validity, and incremental validity were also examined.ResultsThe exploratory factor analysis yielded a 13-item solution consisting of three factors: social situations outside of school, school situations, and home and family situations. Internal consistency of SMQ factors and total scale ranged from moderate to high. Convergent and incremental validity was also well supported.ConclusionsMeasure structure findings are consistent with the three-factor solution found in a previous psychometric evaluation of the SMQ. Results also suggest that the SMQ provides useful and unique information in the prediction of SM phenomena beyond other child anxiety measures. J. Am. Acad. Child Adolesc. Psychiatry, 2008;47(10):1197–1204.     

A comparative study of obsessive-compulsive disorder in Costa Rica and the United States

This study compares the presentation and expression of obsessive-compulsive symptoms between a Latin-American and North American sample. In Costa Rica (CR) and the United States (US), respectively, 26 and 52 affected individuals with early-onset obsessive-compulsive disorder (OCD) were recruited. The Yale Brown Obsessive Compulsive Scale (YBOCS), a semi-structured psychiatric interview, and self-report questionnaires were administered. Age of onset and the distribution of OCD across men and women were similar across groups. Both CR and US participants reported obsessions and compulsions, with similar frequencies of symptoms, and contamination, symmetry, and hoarding as the most common symptom subtypes. The US sample had higher YBOCS total severity scores than the Costa Rican group. Similarly, there were significant ethnicity effects for YBOCS compulsion [F(1, 70)=17.88, P<.001] and obsession severity [F(1, 70)=8.78, P<.001], with Caucasians having higher scores than Costa Ricans on both subscales. Comorbidity rates were higher for US Caucasians than Costa Ricans for all disorders; differences were significant for mood disorders [64.7% versus 34.6%], alcohol use [21.3% versus 3.8%], cannabis use disorders [19.1% versus 0%], and other substance use disorders [39.4% versus 0%]. Regression analyses revealed that ethnicity, trait anxiety, and proband status were the only significant predictors of total YBOCS severity. Findings suggest that the core phenotype of OCD is the same in both CR and the US, and perhaps biologically driven. However some features of OCD, such as impairment, may be culturally influenced, leading to differences in prevalence rates and treatment utilization.