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Journal Article 2006; 27(4): 401-413 PubMed PMID: 16807526 Citation  Keywords:  Child, Preschool, Developmental Disabilities:chemically induced, Diphtheria-Tetanus-Pertussis Vaccine:adverse effects, Haemophilus Vaccines:adverse effects, Humans, Nervous System Diseases:chemically induced, Thimerosal:adverse effects, United States:epid.   

BACKGROUND: Thimerosal is an ethylmercury-containing compound (49.6% mercury by weight) used as at the preservative level in vaccines (0.005% to 0.01%).r />r /> METHODS: Statistical modeling in a meta-analysis epidemiological assessment of the Vaccine Adverse Event Reporting System (VAERS) for neurodevelopment disorders (NDs) reported following Diphtheria-Tetanus-whole-cell-Pertussis (DTP) vaccines in comparison to Diphtheria-Tetanus-whole-cell-Pertussis-Haemophilus Influenzae Type b (DTPH) vaccines (administered: 1994-1997) and following Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP), vaccines in comparison to Thimerosal-free DTaP vaccines (administered: 1997-2000), was undertaken.r />r /> RESULTS: Significantly increased adjusted (sex, age, vaccine type, vaccine manufacturer) risks of autism, speech disorders, mental retardation, personality disorders, thinking abnormalities, ataxia, and NDs in general, with minimal systematic error or confounding, were associated with TCV exposure.r />r /> CONCLUSION: It is clear from the results of the present epidemiological study and other recently published data associating mercury exposure with childhood NDs, additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially from Thimerosal-containing vaccines....

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Clinical Trial 2006; 27(3): 307-313 PubMed PMID: 16816836 Citation  Keywords:  Antidepressive Agents, Second-Generation:blood, Antidepressive Agents, Tricyclic:blood, Erythrocyte Membrane:drug effects, Female, Humans, Male, Neurotransmitter Uptake Inhibitors:blood, Plasma:metabolism, Reference Values, Structure-Activity Relationship.   

OBJECTIVE: The distribution of different antidepressants between plasma and red blood cells (RBCs) or between water and erythrocyte membranes (ghosts) has not been sufficiently compared so far.r />r /> MATERIALS AND METHODS: Distribution of seven antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, didesmethylimipramine, dothiepin, and citalopram) was measured in vitro in small volumes of blood or erythrocyte membrane suspension using radiolabeled drugs. Blood samples were taken from healthy subjects.r />r /> RESULTS: The distribution of antidepressants between plasma and RBCs is strongly affected by temperature; however, it does not depend on the antidepressant concentration in the range of their therapeutic concentrations. The data analysis proved that the ratio of RBCs to plasma volume concentrations is the suitable parameter characterizing antidepressant distribution in whole blood. Significantly higher ratios of RBCs to plasma concentrations were found for demethylated metabolites of tricyclic antidepressants and in the case of citalopram. Citalopram showed the highest accumulation in intact RBCs and at the same time the lowest binding to isolated membranes. The binding of drugs to isolated erythrocyte membranes was much higher than in whole blood.r />r /> CONCLUSION: The concentration ratio of antidepressant in RBCs and in plasma is sensitive not only to the binding properties of plasma proteins and cell membranes, but also to changes in drug molecule, both in aminopropyl chain and in aromatic rings. This ratio is to a large extent characteristic of a particular antidepressant....

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Journal Article 2006; 27(3): 345-349 PubMed PMID: 16816835 Citation  Keywords:  Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Male, Middle Aged, RNA, Messenger:analysis, Receptor, Endothelin A:genetics, Receptor, Endothelin B:genetics, Reference Values, Reverse Transcriptase Polymerase Chain Reaction, Tissue Distribu.   

OBJECTIVES: Endothelin is a potent peptide mediator that is synthesized by a number of cells. Previous studies have revealed the occurrence of endothelin in nerve cell bodies of some peripheral ganglia. Endothelin mediates its effects via two distinct receptor subtypes ETA and ETB. The present study was designed to investigate the presence of these two receptors in the human trigeminal ganglion.r />r /> METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to show the presence of mRNA encoding ETA and ETB receptors in the human trigeminal ganglion. To localize the protein immunocytochemistry with antibodies against the endothelin receptors was used.r />r /> RESULTS: Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed mRNA for both receptor subtypes in the human trigeminal ganglion. Immunocytochemistry revealed numerous cell bodies containing the ETA and the ETB receptor proteins.r />r /> CONCLUSIONS: The expression of ETA and ETB receptors in the human trigeminal ganglion suggests a role for endothelin in autonomic and sensory neural transmission....

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Comparative Study 2006; 27(3): 351-354 PubMed PMID: 16816834 Citation  Keywords:  Adenocarcinoma:drug therapy, Animals, Antimetabolites, Antineoplastic:pharmacology, Antineoplastic Agents, Hormonal:pharmacology, Antineoplastic Combined Chemotherapy Protocols:pharmacology, Breast Neoplasms:drug therapy, Cell Line, Tumor, Cell Proliferat.   

OBJECTIVES: Melatonin may influence directly tumor cells through the specific binding sites. The best known melatonin binding sites are membrane receptors. Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR receptors in oncostatic action of melatonin on the breast cancer has been widely discussed. The aim of present study was to investigate effects of melatonin, the selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on growth of murine 16/C breast cancer cells.r />r /> MATERIAL AND METHODS: The experiment was performed in vitro. The breast cancer cells were incubated for 2 days in the presence of melatonin, CGP 52608 (at concentrations of 10(-5)M, 10(-7)M, 10(-9)M, 10-(11)M ) and methotrexate (at concentrations of 0.25 and 0.125 microg/ml). The growth of cells was measured using the modified Mossman method.r />r /> RESULTS: All examined compounds significantly inhibited the growth of cancer cells. The effects of MLT and CGP 52 608 were comparable with suppression caused by methotrexate. The significant differences of efficacy between two examined concentrations of methotrexate were not observed.r />r /> CONCLUSION: The obtained data together with our previous results indicate that nuclear receptors RZR/ROR play an important, although not sufficiently recognized role in the oncostatic action of melatonin....

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Controlled Clinical Trial 2006; 27(3): 373-380 PubMed PMID: 16816833 Citation  Keywords:  Bottle Feeding, Chronobiology Phenomena:physiology, Circadian Rhythm:physiology, Double-Blind Method, Feeding Behavior:physiology, Female, Humans, Infant, Infant Formula:pharmacology, Infant Nutritional Physiological Phenomena, Infant, Newborn, Male, Nucl.   

: On the basis of the circadian nutritional variations present in breast milk, and of the implications for the sleep/wake cycle of the nutrients present in infant formula milks, we designed a formula milk nutritionally dissociated into a Day/Night composition. The goal was to improve the bottle-fed infant's sleep/wake circadian rhythm. A total of 21 infants aged 4-20 weeks with sleeping difficulties were enrolled in the three-week duration study. The sleep analysis was performed using an actimeter (Actiwatch) placed on an ankle of each infant to uninterruptedly record movements during the three weeks. The dissociated Day milk, designed to be administered from 06:00 to 18:00, contained low levels of tryptophan (1.5g/100g protein) and carbohydrates, high levels of proteins, and the nucleotides Cytidine 5 monophosphate, Guanosine 5 monophosphate and Inosine 5 monophosphate. The dissociated Night milk, designed to be administered from 18.00 to 06.00, contained high levels of tryptophan (3.4g/100g protein) and carbohydrates, low levels of protein, and the nucleotides Adenosine 5 monophosphate and Uridine 5 monophosphate. Three different milk-feeding experiments were performed in a double-blind procedure covering three weeks. In week 1 (control), the infants received both by day and by night a standard formula milk; in week 2 (inverse control), they received the dissociated milk inversely (Night/Day instead of Day/Night); and in week 3, they received the Day/Night dissociated formula concordant with the formula design. When the infants were receiving the Day/Night dissociated milk in concordance with their environment, they showed improvement in all the nocturnal sleep parameters analyzed: total hours of sleep, sleep efficiency, minutes of nocturnal immobility, nocturnal awakenings, and sleep latency. In conclusion, the use of a chronobiologically adjusted infant formula milk seems to be effective in improving the consolidation of the circadian sleep/wake cycle in bottle-fed infants....

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Clinical Trial 2006; 27(3): 355-358 PubMed PMID: 16816832 Citation  Keywords:  Aged, Amyotrophic Lateral Sclerosis:drug therapy, Analysis of Variance, Dopamine:metabolism, Erythropoietin:metabolism, Female, Humans, Hypothalamo-Hypophyseal System:drug effects, Injections, Intravenous, Male, Middle Aged, Neuroprotective Agents:metabol.   

OBJECTIVES: The presence of erythropoietin (EPO) and its receptors in several central nervous system regions indicates additional functions beside its hematopoietic role. Preclinical data suggest that it may slow down the process of neuronal loss, and that EPO may cause dopamine release, and thus influence hormone release, especially prolactin. This possibility has not yet been studied in humans.r />r /> METHODS: During a clinical trial on possible protective effects in patients with amyotrophic lateral sclerosis (ALS), we studied the acute effects of EPO administration on prolactin, the release of which is under tonic inhibition of hypothalamic-pituitary dopaminergic activity. Prolactin as well as EPO levels were estimated in blood samples taken every 30 min over 2 hours after administration of 3000 IU EPO i.v. in seven male and four female patients with ALS.r />r /> RESULTS: The baseline PRL levels of the 11 patients were all within normal range (4.5-10.5 ng/ml). EPO administration caused a significant reduction in prolactin levels, maximal at 60 min after administration. Reductions in PRL were not related to EPO dose (IU per kg body weight), or to duration of illness.r />r /> CONCLUSIONS: The findings indicate that EPO promotes dopamine release in humans, and is consistent with preclinical data showing that EPO releases dopamine from rat striatal slices. Previous reports showed that dopaminergic neurons express EPO receptors, which exert a facilitating action on dopamine release, and the present data indicate that this may hold true in humans....

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Comparative Study 2006; 27(3): 359-364 PubMed PMID: 16816831 Citation  Keywords:  Adult, Analysis of Variance, Circadian Rhythm:physiology, Estradiol:blood, Female, Follicular Phase:blood, Humans, Linear Models, Luteinizing Hormone:blood, Ovulation:blood, Periodicity, Progesterone:blood, Reference Values, Substance P:blood,.   

OBJECTIVES: In order to determine the exact pattern of plasma Substance P (SP) concentration during the LH preovulatory surge and the functional correlates which could exist between plasma SP, LH, 17 beta-estradiol (E2) and Progesterone, we performed a detailed analysis of changes in plasma SP concentration, during the critical phases of the LH preovulatory surge in the Human.r />r /> METHODS: The experimental study was performed in 21 women between the ages of 26 and 35 years. For each subject, blood samples were taken every 15 min, between 07:00 a.m. and 09:00 a.m. for 3 consecutive days when E2 plasma values reached at last 125 pg/ml. Then, each subject, according to the mean LH value of each day, was classified into one of the following groups: 1) the day before the day of the ascending phase, 2) the day of the ascending phase, 3) The day of the LH surge, 4) the day of the descending phase, 5) the day after the day of the descending phase.r />r /> RESULTS: Mean SP plasma values for the day of the LH peak, the day of the descending phase and the day after the day of the descending phase were all significantly higher than the values of the day of the ascending phase. Overall, there was an almost linear increase for plasma SP values between the day before the day of the ascending phase and the day after the day of the descending phase Also,this linear increase in plasma SP concentration exhibited a positive correlation (p = 0.016) with plasma progesterone concentrations which also started to increase on the day of the ascending phase of the LH surge.r />r /> CONCLUSIONS: Taken together with previous results which have shown that the administration of a SP antagonist reduces both the amplitude and the duration of the preovulatory LH surge in the monkey, the increase in plasma SP concentrations, possibly driven by the rise in serum progesterone concentration, which take place at the time of the preovulatory LH surge, is certainly an important element of the Hypothalamo-Pituitary-Gonadal interactive network necessary for the full development of the preovulatory LH surge in the Human....

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Comparative Study 2006; 27(3): 365-368 PubMed PMID: 16816830 Citation  Keywords:  Animals, Female, Glutathione:metabolism, Glutathione Peroxidase:metabolism, Glutathione Transferase:metabolism, Kidney:enzymology, Liver:enzymology, Male, Melatonin:physiology, Mice, Random Allocation,.   

OBJECTIVES: The changes in reduced glutathione (GSH), activity of glutathione transferase (GST) and glutathione peroxidase (GSPx) after administration of exogenous melatonin (N-acetyl-5-methoxy-tryptamine) at a dose 20 mg/kg b.w. were investigated for five and ten days in the liver and kidney of male and female mice.r />r /> METHODS: The liver and kidney were homogenized in 0.1 M phosphate buffer. Glutathione level and activity of studied glutathione enzymes were determined in the supernatants.r />r /> RESULTS: Melatonin caused an increase in glutathione level, the activity of glutathione peroxidase as well as glutathione transferase in the examined organs.r />r /> CONCLUSION: Melatonin may exert some effects on the activity of enzymes engaged in the metabolism of thiol compounds in the cell. Glutathione may be useful for monitoring melatonin's protective role on cell damage....

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