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Journal Article 2005; 26(Suppl 1): 27-47 PubMed PMID: 16361987 Citation  Keywords:  Antidepressive Agents, Second-Generation:therapeutic use, Antipsychotic Agents:therapeutic use, Bipolar Disorder:drug therapy, Clinical Trials as Topic, Depressive Disorder:diet therapy, Humans, Treatment Outcome,.   

: Antidepressants have insufficient effect in 20-40% of patients treated for depressive disorders. This is particularly true for psychotic and agitated depression. When administered on a long-term basis, antidepressants cause a switch into mania in 25-40% of patients and induce rapid cycling. Classical antipsychotics have exhibited good therapeutic efficacy in the treatment of various forms of depression, especially psychotic and agitated forms, albeit burdened with many, above all extrapyramidal, side effects. When administered over long periods of time, classical antipsychotics may have a depressogenic effect. Second-generation antipsychotics have started to be increasingly used in this indication for a variety of reasons including: their antidepressant effect attributable to raised concentrations of catecholamines in the prefrontal cortex, their impact on serotonin transmission, their antipsychotic effect due to their mode of action including the mesolimbic blockade of dopamine D2 receptors, and the low incidence of extrapyramidal and other side effects. The following text encompasses the results of controlled trials using second-generation antipsychotics in the treatment of acute depressive disorders....

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Journal Article 2005; 26(1): 51-54 PubMed PMID: 15726020 Citation  Keywords:  Animals, Carcinogens:administration & dosage, Cell Survival:drug effects, Diethylstilbestrol:administration & dosage, Drug Implants, Hypoglycemic Agents:pharmacology, Ligands, Male, PPAR gamma:drug effects, Pituitary Neoplasms:chemically induced, Prolacti.   

OBJECTIVES: PPAR-gamma is a member of the nuclear receptor superfamily. PPAR-gamma activation is associated with glucose metabolism regulation, adipocyte differentiation, inhibition of macrophage and monocyte activation and anti-angiogenesis. PPAR-gamma ligands thiazolidinediones (TZDs) have been shown to inhibit the growth and secretory activity of several rat and murine pituitary tumors in vivo as well as in vitro (ACTH-secreting AtT20, PRL- and GH-secreting GH3, LH-secreting LbetaT2 and alpha-T3 cells). TZDs have been demonstrated to induce G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, murine corticotroph and gonadotroph pituitary tumor cells. In the present study we have investigated for the first time the effects of PPAR-gamma receptor ligand rosiglitazone on the rat estrogens-induced, PRL-secreting pituitary tumor cells in vitro.

MATERIAL AND METHODS: Four weeks old male Fischer 344 rats were used in the experiment. Pituitary tumors were induced by subcutaneous implantation of capsules containing diethylstilboestrol (DES). Eight weeks after the implantation of capsules the rats were sacrificed and pituitary tumors were collected. Tumorous cells were isolated and exposed in the primary culture to rosiglitazone at the concentrations 10(-10) - 10(-4)M for 24 hours. The cell growth was estimated by the measurement of the cells metabolic activity using the EZ4U system.

RESULTS: We have demonstrated that rosiglitazone at the concentrations 10(-10) - 10(-4)M significantly decreases the number of viable rat PRL-secreting pituitary tumor cells in vitro.

CONCLUSION: These results suggest that PPAR-gamma receptor agonists thiazolidinediones may be useful in the medical treatment of pituitary tumors....

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Journal Article 2001; 22(5): 343-348 PubMed PMID: 11600876 Citation  Keywords:  Animals, Antineoplastic Agents:therapeutic use, Apoptosis:drug effects, Bromocriptine:therapeutic use, Cell Division:drug effects, DNA Fragmentation, Diethylstilbestrol:administration & dosage, Drug Implants, In Situ Nick-End Labeling, Male, Octreotide:th.   

OBJECTIVES: The purpose of the study was to compare the effects of bromocriptine (BC) - D-2 receptor agonist and octreotide (OCT) - somatostatin analog on the tumor weight, prolactin (PRL) secretion, cell proliferation and apoptosis in the diethylstilboestrol (DES)-induced rat prolactinoma.

MATERIAL AND METHODS: Male four-week Fisher 344 rats were used in the experiment. The animals were implanted subcutaneously (s.c.) with capsules containing DES. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24 h s.c.) or BC (3 mg/kg b.w./24 h s.c.) for 10 days. The incorporation of bromodeoxyuridine (BrDU) into the tumor cell nuclei was used as an index of cell proliferation (labeling index - LI). The labeling of nuclear DNA fragmentation according to the TUNEL method was considered as an index of apoptosis (AI). PRL was measured by radioimmunoassay (RIA).

RESULTS: It has been found that OCT and BC significantly decreased the tumor weight and LI of tumor cells to the same extent. Both OCT and BC suppressed the PRL levels, but the inhibitory effect of BC was stronger than that of OCT. BC and OCT significantly enhanced the number of apoptotic cells in the tumor, but the pro-apoptotic effect of BC was more pronounced. The joint treatment exerted additive effects on tumor mass reduction, PRL secretion and cell proliferation, but OCT attenuated the pro-apoptotic effect of BC.

CONCLUSIONS: Summing up, both OCT and BC inhibit PRL secretion and cell proliferation. The anti-tumoral action of BC, and to some extent the action of OCT, is also connected with induction of apoptosis....

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Journal Article 2018; 39(4): 325-330 PubMed PMID: 30531702 Citation  Keywords:  Adolescent, Adult, Diet, Dietary Exposure, Female, Humans, Meat, Milk, Human:chemistry, Trichothecenes:analysis, Turkey, Young Adult, Zearalenone:analysis,.   

INTRODUCTION: Zearalenone (ZEA) and deoxynivalenol (DON) are toxic fungal secondary metabolites, found mainly in contaminated food, that are associated with serious health problems. It is important to identify undesirable toxins and metabolites that may be present in human milk. The aim of this study was to evaluate human milk ZEA and DON levels, total daily intake of ZEA and DON; and their possible relationship with maternal dietary habits. METHODS: We enrolled 90 lactating mothers who had 7- to 90-day-old babies. A dietary questionnaire was completed by each of the mothers. Human milk samples were obtained from 90 mothers, and human milk ZEA and DON levels were evaluated with the solid-phase direct enzyme immunoassay. The total daily intake (TDI) was calculated for the 63 exclusively breastfed infants. RESULTS: ZEA was detected in all human milk samples; median was 173.8 ng/L (35.7-682 ng/L). The calculated median TDI for ZEA was 33.0 ng/kg body weight (bw) (10.4-120.5 ng/kg) among exclusively breast-fed infants, none of them had a TDI that was above the previously defined threshold levels. Human milk ZEA levels were associated with the maternal consumption of meat, fish, dry fig, dried apricot, flaked red spice and spice. The median DON levels was 3924 ng/L (400-14997 ng/L). The median TDI of DON was 750 ng/kg (240-2774 ng/kg) among exclusively breastfed infants and 36% out of them, the TDI for DON was above the previously defined threshold level. Human milk DON levels were associated with the maternal meat consumption. CONCLUSIONS: Our findings are indicative of dietary exposure to mycotoxins during the pregnancy and lactation periods in nursing mothers. Further, the excessive TDI values for DON observed in 36% of the exclusively breastfed infants point to the need for further regulations and recommendations on the dietary habits of pregnant/nursing mothers in order to avoid exposure to potential mycotoxins....

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Journal Article 2019; 39(7): 501-514 PubMed PMID: 30860682 Citation  Keywords:  Biomarkers:blood, Dietary Supplements:adverse effects, Double-Blind Method, Female, Ferritins:blood, Folic Acid:blood, Glycated Hemoglobin A, Homocysteine:blood, Humans, Iron:blood, Male, Prospective Studies, Sex Factors, Time Factors, Vitamin B 12:blood,.   

OBJECTIVES: Pregnancy is a period in life with a high demand of micronutrients. A prophylactic supplementation of folic acid to reduce the risk of neurological malformations in the newborn is common practice. The array of essential micronutrients during pregnancy includes neurotropic vitamins (Vitamin B6, B12 and folic acid), minerals like iron, and trace elements like zinc. As the serum level of most micronutritients is actively regulated by the organism, a prophylactic broad supplementation with a mild, but effective supplementation typically does not pose any risk for exaggerated serum levels, therefore prophylactic intake may be prefered to blood screening and specific interventions. METHODS: To investigate the ingredients' bioavailability of the complex vitamin-mineral-trace element composition LaVita® we recruited healthy volunteers for six months and observed the changes of pregnancy relevant parameters by means of laboratory measures. The study design was prospective, double blind, placebo controlled, and included a "male group control". We determined baseline parameters of folate, vitamin B6 and vitamin B12, iron, zinc, homocysteine and Hb-alpha-1c. After three and six months of daily intake of the study substance the blood tests were repeated and compared to the baseline levels. RESULTS: The regular intake resulted in an increase of the supplemented substances' serum levels. The metabolic parameter homocysteine decreased significantly, Hb-alpha-1c was slightly lowered. CONCLUSION: The regular intake filled up the respective storage compartments and reservoirs in the tissues, and improved the metabolic status. Female participants tended to benefit more than male. We conclude that the composition is safe, and warrants optimized micronutrient supply during pregnancy or postnatal breastfeeding....

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