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Journal Article 2006; 27(4): 539-546 PubMed PMID: 16891988 Citation  Keywords:  Animals, Astrocytes:physiology, Brain Injuries:pathology, Capillaries:metabolism, Cell Differentiation:physiology, Cerebral Cortex:blood supply, Endoplasmic Reticulum:metabolism, Endothelium, Vascular:cytology, Immunohistochemistry, Male, Microscopy, Elec.   

OBJECTIVES: We investigated neovasculatization in the cerebral cortex of the adult rat after surgical brain injury by ultrastructural, immunocytochemical and immunochemical means. Previously we described endothelial-like cell that participates in new vessel formation on plasma proteins that served as a provisional matrix in the region immediately adjacent to the traumatic injury. In the present study we describe new vessel formation in the multistep process with the alterations in endothelial-like cell immunophenotype.

METHOD: The observations were conducted from 2 to 7 days after induction of cortical trauma. Traumatic injury was induced in the frontotemporal region of cerebral cortex.

RESULTS: We show that endothelial-like cell could not successfully terminate its development without the presence of pericyte and astrocyte. New formed blood vessels were accompanied by fibroblast and lipofibroblast cells differentiated probably from common progenitor.

MAIN FINDINGS: Our result suggests that endothelial-like cell is committed endothelial cell between progenitor endothelial cell and terminally differentiated endothelium stage. Therefore, we propose that our of endothelial stem cells present in blood at different stages of morphogenetic differentiation and specifically arrested in "check points" of development trauma mobilize the group of the most differentiated progenitors. These may contribute to new vessel formation.

CONCLUSION: Our model should be useful for the characterization of endothelial commitment and endothelial cell differentiation after brain injury....

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Comparative Study 2006; 27(4): 493-500 PubMed PMID: 16891987 Citation  Keywords:  Adiponectin:blood, Adipose Tissue:metabolism, Adult, Aged, Aged, 80 and over, Aging:metabolism, Blood Pressure, Body Mass Index, Cholesterol, HDL:blood, Cholesterol, LDL:blood, Energy Metabolism:physiology, Female, Humans, Insulin:metabolism, Insulin Resi.   

OBJECTIVES: Adipose tissue secretes proteins which regulate energy metabolism and insulin sensitivity. Adiponectin possesses anti-diabetic, anti-atherogenic and insulin-sensitizing properties. To assess the prognostic factors in prolonged survival and the potential protective role of adiponectin in aging, we examined the release of adiponectin in relation to the metabolic status of centenarians, compared with young, early elderly and obese subjects.

MATERIAL AND METHODS: The study was carried out on 122 women: 22 centenarians aged 100-102 yrs, 45 younger women aged 20-43 yrs, 19 early elderly women aged 64-67 yrs, and 36 obese women aged 26-54 yrs. Anthropometric data, clinical features and blood samples were obtained. Plasma adiponectin and insulin concentrations were measured by RIA methods. Fasting plasma glucose levels, lipid profile and creatinine concentrations were determined using routine laboratory procedures.

RESULTS: In centenarians we found that adiponectin concentrations were significantly increased, compared with young, early elderly and obese women. Insulin concentrations were lower than those in young and obese subjects. HOMA-IR was significantly lower than in obese women. Positive correlations were found between adiponectin and HDL, and negative correlations between adiponectin and HOMA-IR, total cholesterol, LDL, triglycerides, blood pressure and BMI.

CONCLUSION: Our results indicate that adiponectin may play a protective role that contributes to longevity....

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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%).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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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