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Comment 2005; 26(6): 757-758 PubMed PMID: 16380670 Citation  Keywords:  Circadian Rhythm:drug effects, Diabetes Mellitus, Type 2:blood, Double-Blind Method, Humans, Hydrocortisone:blood, Hypoglycemic Agents:pharmacology, Hypothalamo-Hypophyseal System:drug effects, PPAR gamma:agonists, Pituitary-Adrenal System:drug effects, T.   

OBJECTIVES: PPAR-gamma agonists are able to inhibit pituitary tumour development and tumoral hormonal secretion in rodents both in vitro and in vivo. Their use for treatment of Cushing Disease (CD) has been suggested but the clinical experience with the two PPAR-gamma agonists commercially available (rosiglitazone and pioglitazone) was not impressive. Short-time treatment has been proposed to be the cause of unsuccessful results on CD in humans. We report here the effect on early-morning plasma cortisol levels of a long-time treatment with rosiglitazone at the highest approved dose.

METHODS: Because PPAR-gamma receptors are located in normal corticotroph cells we tested in a placebo-controlled study the influence of rosiglitazone on cortisol secretion. The study enrolled 30 newly diagnosed type 2 patients which were assigned to receive either rosiglitazone (8 mg/day) or placebo. Plasma morning cortisol (8.00 a.m.) was measured at the baseline and at the end of the study.

RESULTS: Rosiglitazone vs placebo did not modify the early morning plasma levels of cortisol (13 microg/dl [3-21] vs 11 microg/dl [7-23] [median and range]) after 26 weeks of treatment.

CONCLUSION: The discrepancy between in vitro and animal data on one side and clinical data on the other side warrant further investigations into the mechanisms of action of PPAR-gamma agonists on ACTH secretion before other clinical studies will be conducted....

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Clinical Trial 2005; 26(5): 447-452 PubMed PMID: 16264418 Citation  Keywords:  Adolescent, Aging:physiology, Body Height:drug effects, Child, Female, Growth Hormone:therapeutic use, Hormones:blood, Human Growth Hormone:deficiency, Humans, Magnetic Resonance Imaging, Male, Pituitary Gland:anatomy & histology, Predictive Value of Test.   

INTRODUCTION: Certain relationships between pituitary size and growth hormone (GH) secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy.

AIM: Evaluation of relations between GH secretion and the pituitary size in short children and estimation of the efficacy of GH therapy in children with GH deficiency (GHD).

PATIENTS AND METHODS: The analysis comprised 216 short children (159 boys). Two GH stimulation tests, as well as magnetic resonance image (MRI) examination, were performed in each patient. All the patients with GHD were treated with GH for, at least, one year.

RESULTS: Significant correlations were found between pituitary height and GH secretion (p < 0.05). Patients were classified into three (3) groups: 1) pituitary hypoplasia (HP) for height age; 2) HP for the chronological age but not for the height age; 3) normal pituitary size. Significant differences in GH secretion were observed among the groups (6.1+/-5.3 vs. 8.1+/-4.4 vs. 12.3+/-9.1 ng/mL, respectively). There was a negative correlation between GH peak and height gain during GH therapy (r = -0.34). The highest growth improvement was noticed in patients with HP for the height age.

CONCLUSIONS: Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy....

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Journal Article 2005; 26(5): 480-486 PubMed PMID: 16264415 Citation  Keywords:  Adult, Antibodies, Protozoan:analysis, Blood Donors:psychology, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior:physiology, Female, Humans, Male, Personality Tests, Reward, Toxoplasmosis:immunology,.   

OBJECTIVES: Toxoplasma gondii, a parasitic protozoan, infects about 30 - 60% of people worldwide. Toxoplasma is known to induce behavioral changes and an increase of dopamine in mice. The presence of anti-Toxoplasma antibodies (latent toxoplasmosis) is also a risk factor for schizophrenia. Latent toxoplasmosis in men (male soldiers) is associated with lower novelty seeking. As the novelty seeking is supposed to negatively correlate with level of dopamine, the observed effect was interpreted as indirect evidence of increased dopamine levels in subjects with toxoplasmosis. However, it is also possible that the observed effect was caused by association of both novelty seeking and Toxoplasma infection with a third factor, e.g. size of place of residence.

METHODS: Personality profile of 290 blood donors (205 men and 85 women) were measured by Cloninger's TCI (Temperament and Character Inventory) and their blood samples were assayed for the presence of anti-Toxoplasma antibodies. Difference between Toxoplasma-infected and Toxoplasma-free subjects was tested with ANCOVA method with gender, size of place of residence, and age as covariates.

RESULTS: The present analysis revealed that lower novelty seeking was associated with latent toxoplasmosis both in men and women. The effect of infection on novelty seeking remained significant even after adjustment for size of place of residence (p<0.01).

CONCLUSION: Decreased novelty seeking in Toxoplasma-infected subjects have been already confirmed in three independent populations (male soldiers and male and female blood donors). These findings suggest that the local inflammation-induced increase in dopamine in the brain of infected subjects can represent a missing link between toxoplasmosis and schizophrenia....

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Journal Article 2005; 26(5): 487-492 PubMed PMID: 16264414 Citation  Keywords:  Aging:metabolism, Antigens, CD:metabolism, Antigens, CD3:metabolism, Antigens, Differentiation, T-Lymphocyte:metabolism, Biomarkers, CD8-Positive T-Lymphocytes, Dehydroepiandrosterone Sulfate:blood, Fatigue Syndrome, Chronic:blood, Female, Humans, Inflamm.   

: There are a few reports that chronic fatigue syndrome (CFS) may be accompanied by changes in hormones, such as dehydroepiandrosterone (DHEA) and insulin-like growth factor (IGF1). This study examines the serum concentrations of DHEA-sulfate (DHEAS), IGF1 and IGF1 binding protein-3 (IGFBP3) in 20 patients with CFS and in 12 normal controls. The IGFBP3/IGF1 ratio was computed as an index for IGF1 availability. We found significantly lower serum DHEAS concentrations in CFS, but no significant differences either in IGF1 or the IGFBP3/IGF1 ratio between CFS patients and normal controls. The decrease in serum DHEAS was highly sensitive and specific for CFS. There were significant and positive correlations between serum DHEAS and serum zinc and the mitogen-induced expression of the CD69 molecule on CD3+CD8+ T cells (an indicator of early T cell activation). There was a significant and negative correlation between serum DHEAS and the increase in the serum alpha-2 protein fraction (an inflammatory marker). Serum IGF1, but not DHEAS, was significantly and inversely correlated to age. The results show that CFS is accompanied by lowered levels of DHEAS and that the latter may play a role in the immune (defect in the early activation of T cells) and the inflammatory pathophysiology of CFS....

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Clinical Trial 2005; 26(5): 493-498 PubMed PMID: 16264413 Citation  Keywords:  Adult, Circadian Rhythm:physiology, Humans, Light, Lighting, Male, Melatonin:blood, Middle Aged, Photic Stimulation, Pupil:physiology, Retina:physiology, Signal Transduction:physiology,.   

OBJECTIVES: Published data, both on nocturnal melatonin suppression in humans and on widely accepted retinal structure and function, suggest that spectral opponency plays a role in human circadian phototransduction. We directly test subadditivity, implied by spectral opponency, in human circadian phototransduction in response to nearly monochromatic and to polychromatic light.

METHODS: Adult male human subjects were exposed for 60 minutes to two intensities each of two lighting conditions, during nighttime experimental sessions. One condition consisted of light from mercury vapor lamps (450 and 1050 lx), and one condition consisted of light from these lamps filtered such that only the spectral line from this lamp at 436 nm was presented to subjects (7.5 and 15 lx).

RESULTS: Melatonin suppression from the filtered illumination at 436 nm alone was greater than mercury lamp illumination (containing energy at 436 nm in addition to other wavelengths), even when the sources exposed subjects' retinae to equal amounts of irradiance at 436 nm.

CONCLUSION: This direct test of subadditivity, together with evidence from neuroanatomy, supports the inference that spectral opponency is a fundamental characteristic of human circadian phototransduction....

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Journal Article 2005; 26(5): 439-446 PubMed PMID: 16264412 Citation  Keywords:  Autistic Disorder:chemically induced, Autoimmune Diseases:chemically induced, Chelating Agents:therapeutic use, Child, Humans, Inflammation:chemically induced, Mercury:analysis, Mercury Poisoning:epidemiology,.   

: The causes of autism and neurodevelopmental disorders are unknown. Genetic and environmental risk factors seem to be involved. Because of an observed increase in autism in the last decades, which parallels cumulative mercury exposure, it was proposed that autism may be in part caused by mercury. We review the evidence for this proposal. Several epidemiological studies failed to find a correlation between mercury exposure through thimerosal, a preservative used in vaccines, and the risk of autism. Recently, it was found that autistic children had a higher mercury exposure during pregnancy due to maternal dental amalgam and thimerosal-containing immunoglobulin shots. It was hypothesized that children with autism have a decreased detoxification capacity due to genetic polymorphism. In vitro, mercury and thimerosal in levels found several days after vaccination inhibit methionine synthetase (MS) by 50%. Normal function of MS is crucial in biochemical steps necessary for brain development, attention and production of glutathione, an important antioxidative and detoxifying agent. Repetitive doses of thimerosal leads to neurobehavioral deteriorations in autoimmune susceptible mice, increased oxidative stress and decreased intracellular levels of glutathione in vitro. Subsequently, autistic children have significantly decreased level of reduced glutathione. Promising treatments of autism involve detoxification of mercury, and supplementation of deficient metabolites....

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Case Reports 2005; 26(5): 499-502 PubMed PMID: 16264411 Citation  Keywords:  Adrenal Insufficiency:complications, Adrenocorticotropic Hormone:deficiency, Adult, Autonomic Nervous System:physiopathology, Chromosomes, Human, Pair 12:genetics, Conjunctival Diseases:complications, Electroencephalography, Epilepsy:genetics, Hormone Rep.   

: Allgrove syndrome is a rare autosomal recessive disease with achalasia, alacrima, adrenocortical insufficiency, autonomic neuropathy and other neurological disturbances. A case of two brothers with Addison s disease from early childhood is presented. The younger brother with Addison disease died at the age of 5. The older brother was treated for adrenocortical insufficiency from the age 3, and then treated for achalasia and epilepsy from the age of 5. The patient is currently 26 years old and suffers from achalasia and adrenocortical insufficiency. He also suffers from alacrima, autonomic neuropathy, epilepsy and other damages of the central and peripheral nervous system. The clinical picture is typical for Allgrove or 4A syndrome, and the diagnosis was confirmed by means of molecular analysis of a new AAAS gene mutation....

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Journal Article 2005; 26(5): 521-525 PubMed PMID: 16264407 Citation  Keywords:  Adult, Aged, Aging:physiology, Carcinoma, Papillary:genetics, Chromosomes:genetics, Genetic Markers, Humans, Loss of Heterozygosity:genetics, Microsatellite Repeats, Middle Aged, Protein-Tyrosine Kinases:genetics, RNA, Messenger:biosynthesis, Reverse Tran.   

OBJECTIVES: The aim of the study was to establish the LOH frequency of selected polymorphic markers in different histological types of thyroid tumors: 18 colloid goiters (CG), five follicular adenomas (FA), nine follicular carcinomas (FTC), 40 papillary carcinomas (PTC), and one anaplastic carcinoma (ATC). For PTC, tumors negative for RET/PTC rearrangements were preferred.

METHODS: LOH studies were performed using 14 highly polymorphic markers previously described as frequently lost in thyroid tumors.

RESULTS: In 20 cases (27%) the loss of at least one marker was found. No difference between the frequency of the LOH in FTC and PTC tumors was revealed (33% v. 33%). No differences between histopathological subtypes of PTC in LOH were found. Papillary thyroid carcinomas showed a tendency to higher LOH frequency from patients older than 45 years of age compared to younger ones (9/23 v. 4/17) although it was not statistically significant.

CONCLUSIONS: We conclude that papillary thyroid cancers, particularly those diagnosed in patients older than 45 years of age, do exhibit LOH at least with the same frequency as follicular cancers. This increased number of LOH events may contribute to the clinical aggressiveness of cancer in older patients....

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