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Journal Article 2008; 29(3): 313-319 PubMed PMID: 18580855 Citation  Keywords:  Adult, Analysis of Variance, Blood-Air Barrier:physiology, Depressive Disorder, Major:complications, Fatigue Syndrome, Chronic:complications, Female, Humans, Immunoglobulin A:immunology, Immunoglobulin M:immunology, Intestinal Mucosa:physiology, Male, Mid.   

BACKGROUND: It has been shown that chronic fatigue syndrome (CFS) and major depression (MDD) are accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS and MDD are accompanied by an IgM-mediated immune response directed against nitro-serum bovine albumin (BSA), which is a neoepitope of BSA formed by damage caused by nitrosative stress.

AIMS: Toward this end, we examined serum IgM antibodies to nitro-BSA in 13 patients with CFS, 14 subjects with partial CFS, 16 patients with MDD and 11 normal controls.

RESULTS: We found that the prevalence and mean values for the serum IgM levels directed against nitro-BSA were significantly greater in patients with partial CFS, CFS and MDD than in normal controls, and significantly greater in CFS than in those with partial CFS and MDD. We found significant and positive correlations between serum IgM levels directed against nitro-BSA and symptoms of the FibroFatigue scale, i.e. aches and pain and muscular tension. There was also a strong positive correlation between serum IgM titers directed against nitro-BSA and an index of increased gut permeability ("leaky gut"), i.e. serum IgM and IgA directed against LPS of different gram-negative enterobacteria.

DISCUSSION: The abovementioned results indicate that both CFS and MDD are accompanied by a) an increased gut permeability which has allowed an exaggerated passage of BSA through a compromised epithelial barrier; b) increased nitrosative stress which has induced damage to BSA; and c) an IgM-mediated immune response which is directed against the nitro-BSA neoepitopes. Nitrosative stress is one of the factors underpinning the comorbidity and clinical overlap between CFS and MDD....

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Journal Article 2008; 29(3): 320-327 PubMed PMID: 18580852 Citation  Keywords:  Adolescent, Attention:drug effects, Attention Deficit Disorder with Hyperactivity:epidemiology, Biomarkers, Central Nervous System Stimulants:therapeutic use, Child, Czech Republic:epidemiology, Discrimination (Psychology):physiology, Form Perception:phys.   

OBJECTIVES: The objective was to make a contribution to deepening the knowledge of the etiopathogenesis of ADHD.

DESIGN: In an association study design, an analysis of polymorphisms of selected genes was conducted in 119 hyperkinetic boys and a control group of boys, aged 7-13. Furthermore several psychologically determined subgroups were identified. A connection between psychological functions (endophenotypes) and genes were looked for.

RESULTS: There was a statistically significant difference found in allelic and genotype frequencies of the TaqI A polymorphism of the DRD2 gene. The frequency of the allele A1 in hyperkinetic boys and the control subjects was 0.26 and 0.15, respectively (p<0.003). A statistically significant occurrence of atypical genotypes (8/10, 7/10 and 10/11) of the DAT1 gene was also found in hyperkinetic boys and a connection between the M235 polymorphism of the angiotensinogene gene and the positive family history of psychiatric illness was found in probands (p=0.031). Significant correlations between the results of some neuropsychological tests and genes for neuro-/immunomodulators (IL-6, TNF-alpha) and the gene for the brain-derived neurotrophic factor (BDNF) were found.

CONCLUSION: The study showed a statistically significant prevalence of A1 allele of the DRD gene in the hyperkinetic group. We also found a significantly higher incidence of atypical DAT genotypes in the hyperkinetic group. Furthermore we found significant connections with particular gene polymorphisms which may hypothetically represent a neurodevelopmental risk factor in the etiopathogenesis of the disorder (IL-2, IL-6, TNF-alpha, BDNF). We further found a connection of the M235 polymorphism of the AGT (angiotensinogene) gene to positive family history of psychiatric illness (p=0.031). As for cognitive characteristics, we identified three subtypes with different cognitive performance profiles. This finding shows interindividual variability of cognitive style in the group of hyperkinetic boys....

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Journal Article 2008; 29(3): 341-346 PubMed PMID: 18580851 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Adult, Biomarkers, Body Mass Index, Cohort Studies, Female, Glycopeptides:analysis, Humans, Hydrocortisone:blood, Hypothalamus:metabolism, Male, Middle Aged, Sex Characteristics, Stress, Psychological:metabolism, Vasopre.   

BACKGROUND: During stress, vasopressin is a potent synergistic factor of CRH as a hypothalamic stimulator of the HPA axis. The measurements of CRH and vasopressin levels are cumbersome because of their instability and short half-life. Copeptin is a more stable peptide stoichiometrically released from the same precursor molecule. The aim of our study was to compare copeptin and cortisol levels in different stress situations.

METHODS: Three groups of patients with increasing stress levels were investigated: a) healthy controls without apparent stress (n=20), b) hospitalized medical patients with moderate stress (n=25) and c) surgical patients 30 minutes after extubation, with maximal stress (n=29). In all patients we assessed cortisol and copeptin levels. Copeptin levels were measured with a new sandwich immunoassay.

RESULTS: Cortisol levels in controls were (median, IQ range, 486 [397-588] nmol/L), not significantly different as compared to medical patients (438 [371-612] nmol/L, p=0.69). Cortisol levels in surgical patients after extubation were higher (744 [645-1062] nmol/L p<0.01 vs controls and medical patients). Copeptin levels in controls were 4.3 [3.2-5.5] pmol/L, which was lower as compared to medical patients (17.5 [6.4-24.1], p<0.001) and surgical patients after extubation (67.5 [37.8-110.0] pmol/L, p<0.001). The correlation between copeptin levels and cortisol was r=0.46, p<0.001.

CONCLUSION: Copeptin is a novel marker of the individual stress level. It more subtly mirrors moderate stress as compared to cortisol values....

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Journal Article 2008; 29(3): 334-340 PubMed PMID: 18580850 Citation  Keywords:  Adolescent, Alleles, Antigens, CD:genetics, Autoimmune Diseases:epidemiology, CTLA-4 Antigen, Celiac Disease:epidemiology, Child, Cohort Studies, Diabetes Mellitus, Type 1:epidemiology, Endocrine System Diseases:epidemiology, Female, Genetic Markers, Geno.   

OBJECTIVES: The aim of the study was to determine the association of two CTLA-4 gene polymorphisms (CT60, +49 A/G) with Hashimoto thyroiditis (HT), type 1 diabetes mellitus (T1DM) and celiac disease (CD) as well as with the occurrence of multi-organ involvement by autoimmunity in children.

METHODS: Genotyping was done by RFLP analysis in Slovak children with HT (n=63) and CD (n=120) and both Slovak and Slovene children with T1DM (n=320) and healthy controls (n=231).

RESULTS: We found a significant association of the G allele of the CT60 polymorphism with HT (p<0,0005) in the Slovak population and T1DM in both Slovak (p<0.01) and Slovene populations (p<0.005). The G allele of the +49A/G polymorphism was significantly, though less strongly, associated with T1DM (p<0.05) and HT (p<0.05). Distribution of genotypes of CTLA-4 gene polymorphisms in CD patients did not differ significantly from controls. None of the polymorphisms was associated with multi-organ involvement by autoimmunity.

CONCLUSION: The G allele of both examined CTLA-4 gene polymorphisms predisposes to HT and T1DM, but not to CD. No association with multi-organ involvement was found. The GG genotype of the CT60 polymorphism may identify CD patients at an increased risk for concomitant T1DM and HT. Further studies to assess the predictive value of CTLA-4 polymorphisms for the co-occurrence of HT and T1DM in CD patients are needed....

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Journal Article 2008; 29(3): 366-372 PubMed PMID: 18580848 Citation  Keywords:  Acetyltransferases:metabolism, Animals, Blotting, Western, Dihydroalprenolol:pharmacology, Drugs, Chinese Herbal:pharmacology, Male, Melatonin:biosynthesis, Pineal Gland:drug effects, Plant Extracts:pharmacology, RNA, Messenger:biosynthesis, Radioimmunoas.   

OBJECTIVES: The purpose of this study is to investigate if the aqueous extract of the Chinese medicine Danggui-Shaoyao-San (DSS) can increase the plasma level of melatonin and enhance the function of the pineal gland of naturally aged rats.

METHODS: The rats were treated with DSS at doses of 3ml or same volume of distilled water by oral administration at 11 p.m. for three weeks. The plasma level of melatonin were measured by radioimmunoassay. The function of pineal gland were measured through three parameters: pineal beta adrenergic receptor binding investigated by [3H]DHA binding; pineal expression of NAT mRNA detected by real-time RT-PCR; phosphorylation of CREB (P-CREB) and total level of CREB (T-CREB) measured by western blot analysis.

RESULTS: DSS significantly increased melatonin level at night after oral administration for 3 weeks. By measurement of pineal [3H]DHA binding, it was found DSS improved the beta-adrenergic receptors binding in pineals. The stimulatory effect of DSS on the expression of NAT mRNA in the old rat pineal gland has been demonstrated in this study. Western blot analysis showed that DSS significantly increased phosphorylation of CREB.

CONCLUSIONS: Our results indicate that a downstream pathway for DSS induction of melatonin synthesis in the rat pineal gland acts via cyclic AMP-dependent cascade and transcription mechanism....

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Journal Article 2008; 29(3): 359-365 PubMed PMID: 18580846 Citation  Keywords:  Adrenal Cortex Hormones:metabolism, Adrenocorticotropic Hormone:blood, Animals, Cell Proliferation:drug effects, Cells, Cultured, Corticosterone:blood, Immunity, Cellular:physiology, Indicators and Reagents, Injections, Intraventricular, Leukocytes:drug e.   

OBJECTIVE: Cocaine-amphetamine regulated transcript peptides (CART) belong to a neuropeptide family expressed in the central nervous system, especially in the hypothalamus, and also in peripheral tissues. The physiological functions of CART include modulation of pituitary hormone release, regulation of body weight, and the control of feeding behavior and metabolic activity. The reciprocal relationships between CART and immune system function have to be established. Therefore, in the present study we aimed to investigate the influence of CART, administered intracerebroventricularly (icv), on selected immune parameters and pituitary-adrenal axis hormone secretion in the rat.

RESEARCH METHODS: In rats submitted to icv infusion of CART or artificial cerebrospinal fluid (aCSF, control) selected immune parameters: splenocyte proliferation (spontaneous and mitogen-stimulated) and peritoneal leukocyte (PTL) activity (spontaneous and phorbol myristate acetate (PMA)-stimulated) were examined 60 and 120 min after treatment. The direct effect of CART on splenocytes in culture in vitro was also examined. Concentration of adrenocorticotrophic hormone (ACTH) and corticosterone was also measured in serum of control and CART infused rats.

RESULTS: Splenocytes isolated 60 min after CART infusion exhibited a decreased, albeit non-significant, ability to proliferate spontaneously and were unable to answering to the mitogenic stimulation. This effect was not seen 120 min after CART treatment, which restored splenocyte proliferation decreased by aCSF infusion. CART addition in vitro did not influence proliferation of splenocytes from control rats. Spontaneous activity of peritoneal leukocytes was not modified by CART infusion. PMA-stimulated PTL activity was significantly decreased in aCSF-infused rats 120 min after treatment and CART infusion antagonized this effect. Non-significant increase in serum cortisol after 60 min followed by a significant decrease after 120 min with no change in ACTH concentration was found.

CONCLUSION: The immunomodulatory activity of icv-infused CART appears to consist in the creation of a short-lasting immunosuppressive internal milieu, followed by the immunostimulatory one. This first effect was most probably due to the activation of the HPA axis and/or other immunosuppressive peptides, but not through the direct action of CART on immune cells. Thus, CART appears to be short-lasting and indirect modulator of immunity....

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Journal Article 2008; 29(3): 292-294 PubMed PMID: 18580844 Citation  Keywords:  Abnormalities, Multiple:surgery, Adult, Amoxicillin:therapeutic use, Anti-Bacterial Agents:therapeutic use, Cesarean Section, Female, Humans, Infant, Newborn, Infant, Premature, Ischium:abnormalities, Kidney Function Tests, Laparotomy, Male, Pelvis:abnorm.   

: We present a case of a pregnancy in a 24 year old woman who was born with ectopia vesicae, split pelvis and hypoplasia of ischial bones. From childhood to adulthood she had undergone reconstructive surgeries of the abdomen and perineum, as well as urine diversion surgery. During pregnancy she experienced recurrent urinary tract infections which were treated with antibiotics. In spite of tocolysis, she delivered by cesarean section a premature baby boy at 35th week of gestation due to premature uterine contractions. The postoperative period was uneventful and they were discharged from the hospital in a good general condition....

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Journal Article 2008; 29(3): 287-291 PubMed PMID: 18580840 Citation  Keywords:  Animals, Anti-Inflammatory Agents:pharmacology, Antidepressive Agents:pharmacology, Biomarkers, Brain Chemistry:drug effects, Cytokines:physiology, Depression:drug therapy, Humans, Inflammation:drug therapy, Intestinal Absorption:physiology, Intestinal Mu.   

: This paper hypothesizes that inflammatory, oxidative and nitrosative (IO&NS) pathways, and an increased translocation of LPS from gram-negative bacteria are causally related to depression following external (psychological) and internal (organic) stressors and that IO&NS pathways are novel targets for antidepressant development. We review that depression is accompanied by an inflammatory reaction as indicated by an increased production of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN)-gamma. These cytokines are stress-sensitive and may cause depressive behaviors. The latter may be induced by an increased catabolism of tryptophan, the precursor of serotonin, to neurotoxic TRYCATs (tryptophan catabolites along the indoleamine oxidase pathway). Inflammatory biomarkers are detected in animal models of depression. Newly developed animal models of depression are based on induced inflammation. Most if not all antidepressants have specific anti-inflammatory effects. Anti-inflammatory compounds may augment the clinical efficacy of antidepressants. Depression is also accompanied by an IgM-related (auto)immune response directed against disrupted lipid membrane components, such as phosphatidyl-inositol, by-products of lipid peroxidation, e.g. azelaic acid and malondialdehyde, and NO-modified amino-acids, which are normally not detected by the immune system but due to damage caused by O&NS have become immunogenic. Increased translocation of lipopolysaccharide from gram-negative bacteria, which may be induced by internal and external stressors, may further aggravate the induced IO&NS pathways....

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