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Journal Article 2005; 26(4): 277-282 PubMed PMID: 16136024 Citation  Keywords:  Adult, Antibodies:immunology, Dental Amalgam:adverse effects, Female, Humans, In Vitro Techniques, Infertility:epidemiology, Interferon-gamma:metabolism, Lymphocyte Activation:drug effects, Lymphocytes:drug effects, Male, Mercury Poisoning, Nervous System.   

INTRODUCTION: Heavy metals can negatively influence the reproduction due to the fact that they are able to impair the immune reactions including autoantibody production in susceptible individuals. In such a way the infertility could be also caused by altered pathologic immune reaction.

AIM OF THE STUDY: To investigate the in vitro lymphocyte reaction after stimulation with metals and production of gamma interferon and antisperm antibodies in supernatants after lymphocyte stimulation in patients with infertility and with proven antisperm antibodies in their serum. The cause of antisperm antibodies presence was not determined.

METHODS: The diagnosis of metal allergy was performed by the lymphocyte proliferation method modified for metals (MELISA) in supernatants of tissue cultures of lymphocytes without the antigen stimulation and after stimulation with mercury chloride, the in vitro production of gamma interferon and antisperm antibodies was studied by ELISA.

RESULTS: More than 50% of patients were reacting to mercury, iron, aluminium and silver as mean by lymphocyte reactivity. When compared the lymphocyte reaction in patients with and without mercury allergy we found that the lymphocytes of patients with mercury intolerance produced less gamma interferon and more antisperm antibodies in supernatants after mercury stimulation of their lymphocytes.

CONCLUSION: In patients with metal intolerance diagnosed by the MELISA test the release of metal ions from dental materials can be one of the stimulating factors which may adversely affect fertility....

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Journal Article 2005; 26(4): 301-304 PubMed PMID: 16136022 Citation  Keywords:  Adolescent, Amenorrhea:blood, Anorexia Nervosa:blood, Appetite:physiology, Body Weight:physiology, Child, Energy Intake, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Humans, Hydrocortisone:blood, Leptin:blood, Luteinizing Hormone:blood, Ne.   

OBJECTIVES: The pathogenesis of anorexia nervosa (AN) remains still unclear. It has been reported that neuropeptides may play a role in the control of appetite and hormone release contributing to hormonal disturbances in AN. However the question if neuropeptide alterations are consequence or cause of malnutrition is still unresolved.

METHODS: Serum leptin, neuropeptide Y (NPY) concentrations as well as hormones (FSH, LH, estradiol, cortisol and fT4) serum levels were prospectively estimated in 19 girls aged 11.7-17.7 years (mean 15.5 years) with anorexia nervosa (AN) at the admission to the hospital (baseline) and at follow-up after 7.21+ 2.32 months of treatment. The treatment consisted of hypercaloric diet, psychotherapy and vitamins supplementation.

RESULTS: Mean leptin concentration significantly increased from 7.99 + 2.6 to 9.98 + 2.48 microg/ml (p<0.01), whereas mean NPY concentration significantly decreased from 34.10 + 9.81 to 29.6 + 8.04 pmol/l (p<0.01). Leptin/BMI ratio was constant, while NPY/BMI ratio decreased. There were no significant differences between leptin and NPY serum concentrations at baseline and follow-up in eumenorrheic vs. amenorrheic patients. Simple linear correlation analysis showed negative correlation between leptin and NPY concentrations at baseline (r=-0.67; p<0.05) and at follow-up (r=-0.76; p<0.05) only in eumenorrheic subgroup. There were no significant correlations between leptin, NPY and BMI and body weight values.

CONCLUSIONS: 1) Serum concentration of leptin increases and serum concentration of NPY decreases significantly during the treatment of anorectic girls. 2) These changes do not correspond with increasing body weight and BMI suggesting disregulation of appetite and body weight control mechanisms in AN. 3) Altered neuroregulation of the neuropeptides (leptin and NPY) secretion may contribute persistent amenorrhea after weight gain in anorectic patients with low initial BMI....

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Comparative Study 2005; 26(2): 89-97 PubMed PMID: 15855878 Citation  Keywords:  Analysis of Variance, Animals, Base Sequence, Hemolymph:metabolism, Humans, Molecular Sequence Data, Morphine:metabolism, Nephropidae:metabolism, Nerve Tissue Proteins:metabolism, Nervous System:metabolism, Nitric Oxide:secretion, Nitric Oxide Synthase:me.   

OBJECTIVES: The study was designed to determine if morphine was present in lobster tissues. It was also important to determine, as in other animals, if its levels would change in response to stress. In this regard, it was also important to determine if lobster immune and neural tissues express the mu opiate receptor subtype, which was coupled to constitutive nitric oxide synthase derived nitric oxide release.

METHODS: Homarus americanus were used in these experiments. Morphine was purified in lobster tissues via high pressure liquid chromatography coupled to UV detection. It was quantified via radioimmunoassay (RIA) and was identified via quadruple time of flight - mass spectrometry. Animals were subject to 2 forms of trauma, namely pereiopod-ablation or lipopolysaccaride (LPS) - injection, and morphine levels determined in nerve cord or hemolymph. Real-time nitric oxide production was determined via an amperometric probe. RT-PCR was used to determine the presence of a micro opiate receptor transcript.

RESULTS: In Homarus americanus hemolymph and nerve cord morphine was found. RIA revealed morphine levels of 3.36 pg/mg +/ - 0.48 SEM (N=8) in nerve cord and 717.88 pg/ml +/ - 56.77 SEM (N=58) in hemolymph. In stressed (pereiopod-ablated or LPS-injected) animals, the endogenous morphine levels initially increased significantly by 24% for hemolymph and 48% for nerve cord. By day 5, the stressed and control values for endogenous morphine, in both tissues, was lower and non-distinguishable. In both hemocytes and neural cells, morphine, not met-enkephalin, stimulated constitutive nitric oxide release in a naloxone antagonizable manner, demonstrating a mu opiate receptor mediated phenomenon and suggesting the presence of the mu opiate receptor subtype, micro3, since it is opiate alkaloid selective and opioid peptide insensitive. RT-PCR revealed the presence of a micro opiate receptor transcript in Homarus neural and immune tissues, which exhibits a 100% sequence identity with its human counterpart.

CONCLUSION: Taken together, after eliminating all sources of contamination, morphine is present in lobster tissues, potentially demonstrating hormonal and neurotransmitter functions that are involved in the animals' stress response....

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Comparative Study 2004; 25(3): 176-177 PubMed PMID: 15349081 Citation  Keywords:  Alzheimer Disease:blood, Cognition:physiology, Humans, Nervous System:physiopathology, Reference Values, Vitamin B 12:blood,.   

: In this contribution we investigated the correlation between plasma vitamin B12 levels and cognitive impairment in Alzheimer's disease. We could demonstrate a significant inverse correlation when the MMSE scores of those patients with the lowest 10% Vitamin B12 plasma levels (<184 ng/ml) were compared with the upper 10% Vitamin B12 plasma levels (>598 ng/ml): p=0.008, Spearman-Rho= -0.36. MMSE in the upper percentile of plasma B12 levels was 20.0 +/- 4.6 and in the lower percentile 15.7 +/- 6.1, resulting in a difference of 4.3 MMSE points. We conclude, that vitamin B12 deficiency could aggravate or accelerate the course of Alzheimer disease as vitamin B12 possesses neuroprotective and anti-inflammatory properties....

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Journal Article 2004; 25(1-2): 24-30 PubMed PMID: 15159678 Citation  Keywords:  Adolescent, Animals, Arachidonic Acids:physiology, Cannabinoid Receptor Modulators:physiology, Central Nervous System:embryology, Child, Child, Preschool, Endocannabinoids, Feeding Behavior:physiology, Humans, Mice, Neuroprotective Agents:metabolism, Poly.   

: Endogenous cannabinoids (endocannabinoids) and their cannabinoid CB1 and CB2 receptors, are present from the early stages of gestation and play a number of vital roles for the developing organism. Although most of these data are collected from animal studies, a role for cannabinoid receptors in the developing human brain has been suggested, based on the detection of "atypically" distributed CB1 receptors in several neural pathways of the fetal brain. In addition, a role for the endocannabinoid system for the human infant is likely, since the endocannabinoid 2-arachidonoyl glycerol has been detected in human milk. Animal research indicates that the Endocannabinoid-CB1 Receptor ('ECBR') system fulfills a number of roles in the developing organism: 1. embryonal implantation (requires a temporary and localized reduction in anandamide); 2. in neural development (by the transient presence of CB1 receptors in white matter areas of the nervous system); 3. as a neuroprotectant (anandamide protects the developing brain from trauma-induced neuronal loss); 4. in the initiation of suckling in the newborn (where activation of the CB1 receptors in the neonatal brain is critical for survival). 5. In addition, subtle but definite deficiencies have been described in memory, motor and addictive behaviors and in higher cognitive ('executive') function in the human offspring as result of prenatal exposure to marihuana. Therefore, the endocanabinoid-CB1 receptor system may play a role in the development of structures which control these functions, including the nigrostriatal pathway and the prefrontal cortex. From the multitude of roles of the endocannabinoids and their receptors in the developing organism, there are two distinct stages of development, during which proper functioning of the endocannabinoid system seems to be critical for survival: embryonal implantation and neonatal milk sucking. We propose that a dysfunctional Endocannabinoid-CB1 Receptor system in infants with growth failure resulting from an inability to ingest food, may resolve the enigma of "non-organic failure-to-thrive" (NOFTT). Developmental observations suggest further that CB1 receptors develop only gradually during the postnatal period, which correlates with an insensitivity to the psychoactive effects of cannabinoid treatment in the young organism. Therefore, it is suggested that children may respond positively to medicinal applications of cannabinoids without undesirable central effects. Excellent clinical results have previously been reported in pediatric oncology and in case studies of children with severe neurological disease or brain trauma. We suggest cannabinoid treatment for children or young adults with cystic fibrosis in order to achieve an improvement of their health condition including improved food intake and reduced inflammatory exacerbations....

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Journal Article 2004; 25(1-2): 14-23 PubMed PMID: 15159677 Citation  Keywords:  Animals, Cannabinoid Receptor Modulators:physiology, Cannabinoids:pharmacology, Cardiovascular Physiological Phenomena:drug effects, Cardiovascular System:drug effects, Central Nervous System:drug effects, Dronabinol:pharmacology, Humans, Psychotropic Dru.   

: Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the pharmacological effects caused by the use of cannabis, is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several countries. The non-psychotropic cannabidiol (CBD), some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues including spleen, leukocytes; reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart. Five endogenous cannabinoids have been detected so far, of whom anandamide and 2-arachidonylglycerol are best characterized. There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of re-uptake into cells and inhibition of their degradation to increase concentration and duration of action. Properties of cannabinoids that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, anti-inflammation, anti-allergic effects, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects....

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Letter 2003; 24(6): 469-473 PubMed PMID: 15073578 Citation  Keywords:  Adrenergic beta-Antagonists:therapeutic use, Autonomic Nervous System Diseases:drug therapy, Humans, Immunity, Cellular:drug effects, Immunocompromised Host:drug effects, Stress Disorders, Traumatic:complications,.   

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Journal Article 2003; 24(6): 431-434 PubMed PMID: 15073570 Citation  Keywords:  Adult, Anorexia Nervosa:metabolism, Appetite:physiology, Diabetes Mellitus:metabolism, Feedback, Physiological, Female, Glucose Tolerance Test, Human Growth Hormone:metabolism, Humans, Hypertension:metabolism, Leptin:blood, Luteinizing Hormone:metabolism,.   

OBJECTIVE: It has been reported that neuropeptides may play a role in the control of appetite and in the mechanism of hormone release. Neuropeptides such as beta-endorphin, neuropeptide Y (NPY), galanin and leptin may affect hormones release, on the other hand the hormonal status may modulate neuropeptide activity.

METHODS: The material consisted of 90 obese women, 30 women with Anorexia Nervosa, and 30 healthy, lean women of control group. Plasma beta-endorphin, NPY, leptin, somatostatin and serum pituitary and gonadal hormones concentrations were measured with RIA methods.

RESULTS: We observed the highest plasma NPY levels in obese hypertensive and diabetic patients. After carbohydrate administration (OGTT) a marked increase of insulin, beta-endorphin and NPY was found. The blunted response of GH to GH-RH may be connected with increased somatostatin activity and hyperinsulinemia. The abnormal response of LH to opioid blockade may be a result of disturbed opioid and NPY activities in obese patients. However in patients with anorexia nervosa, plasma leptin and NPY concentrations were low. The disturbances in beta-endorphin release are also observed.

CONCLUSIONS: The neuroendocrine disturbances in obesity and in anorexia nervosa are opposite. The feedback mechanism between leptin and NPY is disturbed in both in obesity and in anorexia nervosa. An abnormal activity of neuropeptides may lead to disturbed control of appetite and hormonal dysregulation in eating disorders....

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