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Journal Article 2002; 23(1): 45-48 PubMed PMID: 11880861 Citation  Keywords:  Attention Deficit Disorder with Hyperactivity:drug therapy, Attention Deficit and Disruptive Behavior Disorders:metabolism, Central Nervous System Stimulants:therapeutic use, Child, Dextroamphetamine:therapeutic use, Female, Humans, Hydrocortisone:metabol.   

OBJECTIVES: There is growing interest in the role of the hypothalamic-pituitary-adrenal (HPA) axis in neuropsychiatric disorders and there is some evidence that the HPA axis may be underfunctional in behaviorally disturbed children. However, co-morbidity is common in childhood neuropsychiatric disorders. Stimulant medication is widely used in the treatment of Attention-deficit hyperactivity disorder (ADHD) and can increase cortisol secretion when given acutely. We therefore set out to determine the whether salivary cortisol would be reduced in a group of children with ADHD/ODD (Oppositional-defiant disorder) and to examine the effect of stimulant medication on any such relationship.

DESIGN: Salivary cortisol was determined in thirty-two children with co-morbid ADHD and Oppositional-defiant disorder (ODD) according to DSM-IV criteria, compared to twenty-five healthy controls of similar age and ethnic background. Data were analysed according to prescription of stimulant medication in the patient group.

RESULTS: Salivary cortisol was significantly lower in the ADHD/ODD group than in the controls. Further analysis revealed that this reduction was restricted to the subgroup of patients not prescribed stimulant medication.

CONCLUSIONS: The results support the possibility of a dysfunction of control of the HPA axis in these behaviorally disturbed children. A reduction in salivary cortisol could reflect underarousal, an elevated threshold for detection of stressors or a subsensitivity of the HPA axis itself. It remains to be determined whether the ability of stimulant medications to negate the apparent deficit in cortisol secretion in these ADHD/ODD patients is an unrelated consequence of increased dopamine release or a reflection of their therapeutic benefit. The use of stimulant medication for co-existing ADHD should be taken into account in future studies of cortisol in behaviorally disturbed children....

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Journal Article 2002; 23(1): 33-44 PubMed PMID: 11880860 Citation  Keywords:  Adult, Aged, Arginine Vasopressin:antagonists & inhibitors, Aspartic Acid Endopeptidases:metabolism, Female, Glucocorticoids:therapeutic use, Humans, Hypothalamus:metabolism, Male, Middle Aged, Nerve Tissue Proteins:metabolism, Neuroendocrine Secretory Pr.   

OBJECTIVES: We reported earlier that vasopressin (AVP) peptide expression is significantly decreased in the postmortem hypothalamus of glucocorticoid (GC) treated patients, while such a decrease was not observed in AVP prohormone (proAVP) expression. This indicated a GC-induced suppression of AVP synthesis at the posttranslational level. Here, we investigated in detail whether this decreased levels of AVP expression in GC treated patients might be due to the down regulation of the prohormone convertases PC-1 and PC-2, and the molecular chaperone 7B2, as was reported previously in some AVP-related disorders.

MATERIALS & METHODS: An immunocytochemical study was performed on post-mortem hypothalami of GC exposed patients and controls, in which quantification of proAVP, AVP, neurophysin (NP) and oxytocin (OXT) expression were done along with the quantification of PC1, PC2 and 7B2 expression in the paraventricular nucleus, by using a computerized image analysis system.

RESULTS: Expression of processed AVP in GC exposed patients was significantly decreased (p=0.021), while the amount of proAVP expression was unchanged. Despite the strong correlation between AVP and NP (the other cleavage product of proAVP) expression in the GC group (r=0.917, p=0.004), the mean NP immunoreactivity did not show a significant decrease in this group. Also the OXT expression was similar in both groups. Although in most of the GC treated patients, the expression intensities of PC1 and PC2 were decreased parallel to the decrease in AVP, the mean expression levels of neither of PC1 and PC2, nor of 7B2 were statistically different between the groups (p=0.20-0.80).

CONCLUSION: We conclude that the suppression of AVP expression by GCs is not mediated solely by the down regulation of PC1, PC2 or 7B2. Other mechanisms, which may contribute to the GC-induced posttranslational suppression of AVP, are discussed....

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Journal Article 2002; 23(1): 21-26 PubMed PMID: 11880858 Citation  Keywords:  Alkaloids:metabolism, Animals, Blood Vessels:physiology, Endorphins:physiology, Hormones:physiology, Humans,.   

: The distribution of morphine-containing cells in the central nervous system, adrenal gland, and its presence in blood may serve to demonstrate that this signal molecule can act as a hormone besides its role in cell-to-cell signaling within the brain. This speculative review is the result of a literature evaluation with an emphasis on studies from our laboratory. Opioid peptides and opiate alkaloids have been found to influence cardiac and vascular function. They have also been reported to promote ischemic preconditioning protection in the heart. Given the presence of morphine and the novel mu(3) opiate receptor on vascular endothelial cells, including cardiac and vascular endothelial cells in the median eminence, it would appear that endogenous opiate alkaloids are involved in modulating cardiac function, possible at the hormonal level. This peripheral target tissue, via nitric oxide coupling to mu opiate receptors, may serve to down regulate the excitability of this tissue given the heart's high performance state as compared to that of the saphenous vein, a passive resistance conduit. With this in mind, morphine and other endogenous opiate alkaloids may function as a hormone....

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Journal Article 2002; 23(1): 13-20 PubMed PMID: 11880857 Citation  Keywords:  Actomyosin:physiology, Animals, Energy Metabolism, Heart:physiology, Humans, Models, Cardiovascular, Muscle Fibers, Skeletal:physiology, Myocardial Contraction:physiology, Myocardium:metabolism, Ventricular Function,.   

: The aim of this thesis is to investigate the link between biochemical intracellular processes and mechanical contraction of the cardiac muscle. First, the regulation of intracellular energy fluxes between mitochondria and myofibrils is studied. It is shown, that the experimentally observed metabolic stability of the cardiac muscle is reproducible by a simple feedback regulation mechanism, i.e., ATP consumption in myofibrils and ATP production in mitochondria are balanced by the changes of the high energy phosphate concentrations. Second, an important property of energy transformation from biochemical form to mechanical work in the cardiac muscle, the linear relationship between the oxygen consumption and the stress-strain area, is replicated by a cross-bridge model. Third, by using the developed cross-bridge model, the correlation between ejection fraction of the left ventricle and heterogeneity of sarcomere strain, developed stress and ATP consumption in the left ventricular wall is established. Fourth, an experimentally observed linear relationship between oxygen consumption and the pressure-volume area can be predicted theoretically from a linear relationship between the oxygen consumption and the stress-strain area. Summing up, it is shown how the macrovariables of a cardiac muscle are interwoven with intracellular physiological processes into a whole....

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Journal Article 2001; 22(6): 467-474 PubMed PMID: 11781546 Citation  Keywords:  Animals, Cannabinoid Receptor Modulators, Humans, Invertebrates, Neuroimmunomodulation:immunology, Opioid Peptides:immunology,.   

: There is today growing evidence that the nervous and the immune systems can exchange information, mainly through small molecules, either cytokines or neuropeptides. Furthermore, it appears that some so-called neurotransmitters like neuropeptides can function as endogenous messengers of the immune system, and that they most likely participate in an important part in the regulation of the various components of the immune response. In this context, it is widely accepted that all organisms have processes that maintain their state of health. Failure of these processes, such as those involving naturally occurring antibacterial peptides, may lead to pathological events. The presence of antibacterial peptides on both proenkephalin invertebrate (Leeches) and vertebrate (Human) neuropeptide precursors such like enkelytin, peptide B, further supports the hypothesis that some of neuropeptide precursors are implicated in immune response. Indeed, their peptides, with their high antibacterial activities further associate opioid peptides with immune related activities. We surmise that immune signalling molecule may lead to enhanced proenkephalin proteolytic processing by prohormone convertase freeing both opioid peptides and antibacterial peptides during innate immune response. However, because it is necessary to modulate inflammation, invertebrates like leeches are also able to synthesize panoply of messengers that modulate inflammation e.g. endocannabinoids, opiates and pro-opiomelanocortin derived peptides such like adenocorticotrophin and melanostimulating hormone. This demonstrates that the equilibrium between the stimulation and the inhibition of the immune response has evolved sooner that it can be thought....

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Journal Article 2001; 22(6): 461-466 PubMed PMID: 11781545 Citation  Keywords:  Adrenal Glands:chemistry, Animals, Brain-Derived Neurotrophic Factor:analysis, Chromaffin Cells:physiology, Colitis:immunology, Gene Expression:immunology, Glial Cell Line-Derived Neurotrophic Factor, Male, Nerve Growth Factor:analysis, Nerve Growth Facto.   

OBJECTIVES: Neurotrophins and GDNF have been recently recognized as important local regulators of inflammatory processes of the gut.

RESULTS: We now demonstrate that experimental TNBS-colitis is associated with the increased expression of neurotrophins and GDNF in the adrenal glands. In histological sections of the adrenals from untreated control animals, faint immunolabeling for BDNF, NT-3 and NGF was detectable in the adrenal cortex, with some additional labeling for NGF over the adrenal medulla, whereas GDNF immunolabeling was confined to the adrenal medulla. Induction of TNBS-colitis markedly increased NGF, BDNF, and NT-3 expression within the adrenal cortex after 8 h. NGF declined to basal levels after 7 days. In case of BDNF and NT-3 basal expression levels were reached after 14 days. GDNF expression was robustly upregulated in the adrenal medulla 8 h after induction of colitis and stayed elevated for up to 14 days.

CONCLUSION: Together these observations suggest that neurotrophins and GDNF might act as local modulators of components of the HPA-axis during peripheral inflammation....

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Journal Article 2001; 22(6): 453-459 PubMed PMID: 11781544 Citation  Keywords:  Amino Acid Sequence, Animals, Antibody Specificity, Immunohistochemistry, Leeches:enzymology, Male, Nervous System:enzymology, Rabbits, Rats, Rats, Wistar, Renin:analysis, Urinary Tract:enzymology, Water-Electrolyte Balance:physiology,.   

OBJECTIVES: The purpose of this study was to localize in leeches the renin-like enzyme previously characterized as well as the leech angiotensin-converting like enzyme (ACE).

METHODS: Immunocytochemical as well as whole mount experiments were performed with an antibody raised against a fragment of the leech renin-like enzyme (VLWAAEKTQLDTGSS) and with anti-leech ACE.

RESULTS: Anti-leech renin stains the vascular pole of the glomerulus and the afferent arteriole of the rat kidney. Immunostaining of leech sections revealed labeling in neurons and glial cells of the central nervous system (CNS), immunocytes and the nephridial canal, canaliculi and the periphery of the ciliated funnel, as well as the epithelium lining nephridia. Co-localization between antibodies raised against this fragment and a fragment of leech angiotensin-converting enzyme was demonstrated in neurons and glial cells of the leech CNS, as in vertebrates

MAIN FINDING: Leech renin is localized in leeches like in vertebrate in the excretory system and in the nervous system.

CONCLUSIONS: Our findings suggest the presence of a renin-angiotensin system involved in osmoregulation in leeches....

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Journal Article 2001; 22(6): 432-434 PubMed PMID: 11781540 Citation  Keywords:  Animals, Antioxidants:pharmacology, Carcinoma, Ehrlich Tumor:drug therapy, Cattle, Cell Extracts:pharmacology, Male, Melatonin:pharmacology, Mice, Mice, Inbred AKR, Neoplasm Transplantation, Pineal Gland:physiology, Survival Rate,.   

UNLABELLED: OBJECTIVES Pineal gland may have a role in organism's protection against cancer. Melatonin as well as still unidentified low-weight molecular pineal substance(s) have been reported to have growth inhibitory effect on different tumor cells. We tested the influence of melatonin and of a bovine pineal extract on the survival rate of AKR mice inoculated with Ehrlich ascites. The tumor is known to have an accelerated development after pinealectomy.

MATERIAL AND METHODS: Male AKR mice, kept under a 14/10 hours - Light /Dark cycle, were inoculated intraperitoneally (i.p.) with 1.5x 10(6) Ehrlich ascites cells. On day three after inoculation the animals were divided in three groups (n=10). Each animal received i.p. daily (20.00H), until their death, 250 microl of solution containing melatonin (250 microg), pineal extract (equivalent of 1 bovine pineal gland) or saline.

RESULTS: The average survival rate of the animals treated with melatonin was shorter (14.8+/-2.23 days) compared to control animals (21.9+/-2.21 days)(p=0.01). The animals treated with the pineal extract had a longer survival rate (22.6 +/- 1.8 days) but not statistically significant. The pineal extract was not available for testing at higher doses.

CONCLUSION: In our model, melatonin had a deleterious effect on the survival rate raising the question whether it is correct to assume that the hormone shows lack of adverse reactions....

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