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Journal Article 2007; 28(6): 854-860 PubMed PMID: 18063937 Citation  Keywords:  Animals, Antipsychotic Agents:pharmacology, Clozapine:pharmacology, Dose-Response Relationship, Drug, Glucose:pharmacology, In Vitro Techniques, Insulin:secretion, Islets of Langerhans:drug effects, Male, Rats, Rats, Wistar, Statistics, Nonparametric,.   

OBJECTIVES: Treatment with the atypical antipsychotic clozapine is frequently associated with metabolic side-effects such as weight gain, lipid abnormalities and diabetes mellitus. Since insulin is a hormone that is involved in both the regulation of body weight, as well as in lipid metabolism and glucose regulation, an effect of clozapine on insulin secretion and/or on insulin action - at least in part - might explain its capability to induce these side-effects. The aim of this study was therefore to examine the influence of clozapine on insulin release in vitro.r />r /> METHODS: The effect of clozapine in three different concentrations, 10(-6), 10(-5) and 10(-4) M, was investigated on both basal (i.e. 3.3 mM glucose) and glucose-stimulated (i.e. 16.7 mM glucose) insulin release, using isolated rat islets of Langerhans.r />r /> RESULTS: The presence of clozapine in the concentrations of 10(-6), 10(-5) and 10(4 )M significantly increased basal insulin release compared to the control after 4 h (but not after 1 h) of incubation. As regards the glucose-stimulated insulin release, the presence of clozapine in the concentrations of 10(-5) and 10(-4) M, but not in that of 10(-6) M, significantly inhibited the glucose-stimulated insulin release compared to the control after both 1 and 4 h of incubation.r />r /> CONCLUSION: This study demonstrates that the atypical antipsychotic clozapine exerts dual effects on insulin release in vitro, through stimulating basal insulin release and inhibiting glucose-stimulated insulin release. Both these effects of clozapine on insulin release may contribute to its disadvantage inducing metabolic side-effects....

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Journal Article 2007; 28(6): 815-821 PubMed PMID: 18063936 Citation  Keywords:  Adolescent, Adult, Analysis of Variance, Courtship, Female, Genetic Load, Humans, Love, Male, Personality:genetics, Polymorphism, Genetic, Receptor, Serotonin, 5-HT2A:genetics, Receptors, Dopamine D2:genetics, Receptors, Dopamine D4:genetics, Serotonin Pl.   

OBJECTIVES: It has been hypothesized that cerebral neurotransmitters such as dopamine and serotonin could play a role in human romantic bonding. However, no data on the genetic basis of human romantic love are currently available. To address this issue, we looked for associations between markers in neurotransmitter genes (the serotonin transporter gene, 5-HTT; the serotonin receptor 2A, 5HT2A; the dopamine D2 receptor gene, DRD2; and the dopamine D4 receptor gene, DRD4) and the six styles of love as conceptualized by Lee (Eros, Ludus, Storge, Pragma, Mania and Agape).r />r /> DESIGN: A total of 350 healthy young adults (165 males and 185 females, mean age: 24.1+/-3.9 years, range 18-32 years) filled the 24-item Love Attitudes Scale (LAS) and were genotyped for the following six polymorphic markers: the serotonin transporter-linked polymorphic region (5-HTTLPR), the 5HT2A T102C and C516T polymorphisms, the DRD2 TaqI A and TaqI B variants, and the DRD4 exon 3 VNTR polymorphism.r />r /> RESULTS: Statistical analysis revealed a significant association between the DRD2 TaqI A genotypes and "Eros" (a loving style characterized by a tendency to develop intense emotional experiences based on the physical attraction to the partner), as well as between the C516T 5HT2A polymorphism and "Mania" (a possessive and dependent romantic attachment, characterized by self-defeating emotions). These associations were present in both sexes and remained significant even after adjustment for potential confounders.r />r /> CONCLUSIONS: Our data provide the first evidence of a possible genetic loading on human loving styles....

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Journal Article 2007; 28(6): 775-780 PubMed PMID: 18063935 Citation  Keywords:  Acetylation:drug effects, Apoptosis:drug effects, Cell Proliferation:drug effects, Dose-Response Relationship, Drug, Down-Regulation, Enzyme Inhibitors:pharmacology, Histone Deacetylase Inhibitors, Histones:metabolism, Humans, Immunohistochemistry, Multip.   

: The expression of vascular endothelial growth factor receptor 1(VEGFR-1) in human multiple myeloma KM3 cells in vitro, effects of valproic acid (VPA), as a histone deacetylase inhibitor, on cell proliferation and apoptosis and the underlying molecular mechanism were investigated. The effects of VPA on the growth of KM3 cells were studied by MTT assay. The apoptosis rate was determined with flow cytometry. The mRNA level of VEGFR was determined by RT-PCR; and immunocytochemistry was used to detect the protein level of ac-H4 and VEGFR. VPA inhibited proliferation of KM3 cells in a time- and dose-dependent manner. Treatment with VPA (4, 2, 1 and 0.5 mmol/L) for 48h, the apoptosis rates of KM3 cells were (13.27+/-3.54)%, (22.13+/-1.20)%, (24.41+/-2.23)% and(40.62+/-4.28)% respectively. The expression of VEGFR-1 in KM3 cells were decreased in VPA-treated group by the immunochemistry and RT-PCR, whereas the acetylated histone H4(ac-H4) accumulated. It suggested VPA could decrease the expression of VEGFR-1 in KM3 cells, and it might play an important role in regulating the proliferation and apoptosis of multiple myeloma cell line KM3 cells. These results provide the framework for clinical trials....

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Journal Article 2007; 28(6): 861-867 PubMed PMID: 18063934 Citation  Keywords:  Adult, Analysis of Variance, Antibody Formation:immunology, Autoimmunity:immunology, Depression:blood, Depressive Disorder, Major:blood, Fatigue:blood, Fatigue Syndrome, Chronic:blood, Female, Humans, Immunoglobulin M:blood, Male, Middle Aged, Neuropsycho.   

: Major depression and chronic fatigue syndrome (CFS) are accompanied by signs of oxidative and nitrosative stress (O&NS) and an inflammatory response. Phosphatidyl inositol (Pi) is thought to play a role in depression. The aim of the present study is to examine whether depression and CFS are characterized by an IgM-mediated immune response directed against Pi. Toward this end, this study examines the serum IgM antibodies directed against Pi in 14 patients with major depression, 14 patients with CFS, 14 subjects with partial CFS, and in 11 normal controls. We found that the prevalence and mean value for the serum IgM levels directed against Pi were significantly greater in patients with major depression and CFS than in normal controls and patients with partial CFS. There were significant and positive correlations between serum IgM levels directed against Pi and two symptoms of the FibroFatigue Scale, i.e. fatigue and depression. The results show that an IgM-related immune response directed against Pi may occur in both depression and CFS and may play a role in the pathophysiology of the key symptom of CFS and major depression. It is suggested that the above disorders in Pi result from increased O&NS in both depression and CFS. Autoanti-Pi antibodies may have biological effects, for example, by changing inositol 1,4,5-triphosphate (IP3), phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol and phosphatidylinositol-3,4,5-triphosphate (PIP3) production, thus interfering with intracellular signalling processes. Future research in major depression and CFS should focus on the functional consequences of the immune responses directed against Pi....

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Clinical Trial 2007; 28(6): 727-733 PubMed PMID: 18063933 Citation  Keywords:  Acromegaly:drug therapy, Adult, Antineoplastic Agents:administration & dosage, Blood Glucose:metabolism, Delayed-Action Preparations, Drug Administration Schedule, Female, Follow-Up Studies, Homeostasis:drug effects, Human Growth Hormone:blood, Humans, In.   

OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin sensitivity markers among acromegalic patients with pituitary tumors.r />r /> DESIGN: Prospective clinical trial with six months of follow-up.r />r /> SETTING: A tertiary endocrinology clinic.r />r /> MATERIALS AND METHODS: Naïve patients (patient No. 1 and patient No. 3) and patients who experienced prior somatostatin analogue treatment (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after 6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was determined using homeostasis model assessment of insulin resistance and beta-cell function formula. Euglycemic hyperinsulinemic clamp test was also performed to evaluate whole insulin sensitivity and was indicated as an 'M' index.r />r /> RESULTS: All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2 and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The increases in M indices of these patients were with marked decreases in GH levels (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively). Minor decline in HOMA-beta and worsened M index and almost stable GH were observed in patients Nos. 4 and 5. Except for patient No. 3, all participants showed declining HOMA-IR.r />r /> CONCLUSIONS: Short-term Lanreotide Autogel treatment has been observed to improve M indices of acromegalic patients whose GH levels exhibited marked reduction. This amelioration seemed to be related to decreases in GH levels rather than to a direct drug effect....

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Journal Article 2007; 28(6): 841-845 PubMed PMID: 18063932 Citation  Keywords:  Adult, Dopamine Agonists:adverse effects, Female, Follow-Up Studies, Humans, Intracranial Hemorrhages:etiology, Magnetic Resonance Imaging, Male, Pituitary Neoplasms:blood, Prolactin:blood, Prolactinoma:blood, Radiography, Receptors, Dopamine D2:agonists,.   

OBJECTIVES: Retrospective follow-up study on patients suffering from macroprolactinomas which were treated with agonists of D2 receptors; the MRI results were correlated with the clinical symptomatology and with the level of prolactin in the blood.r />r /> METHODS: From 1996 to 2006 we followed 38 patients diagnosed with macroprolactinoma. All patients underwent MRI in same protocol two times. The indication for MRI was based on the clinical symptomatology (signs of hormonal dysfunction, visual fields impairment) or increased blood level of prolactin.r />r /> RESULTS: The first predominant clinical signs in males were local manifestations of expansive process and in women hormonal dysfunction. Intratumorous haemorrhage in patients undergoing the treatment with the agonists of D2 receptors is common, it was encountered in 25 cases, but only in two cases it was followed by a more serious clinical symptomatology, which had to be referred to the department of the neurosurgery. Even when there were pronounced regressions or near complete disappearance of the tumour and normalisation of the blood level of prolactin, withdrawal of the treatment with agonists of D2 receptors caused increase in size of the adenoma and increase of level of prolactinaemia.r />r /> CONCLUSION: Only two patients presented with serious clinical symptomatology associated with intratumoral hemorrhage. The hemorrhages are more common during the first weeks of therapy, but can happen at any time thought out the treatment with D2 receptor agonists. Our hypothesis: the prolactinomas with higher level of prolactin have greater tendency for larger hemorrhages....

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Case Reports 2007; 28(6): 745-748 PubMed PMID: 18063931 Citation  Keywords:  Adrenal Insufficiency:blood, Adrenocorticotropic Hormone:blood, Empty Sella Syndrome:blood, Female, Hormone Replacement Therapy, Humans, Hydrocortisone:blood, Hypoglycemia:blood, Hyponatremia:blood, Methylprednisolone:therapeutic use, Middle Aged, Pituita.   

: Isolated ACTH deficiency is an uncommon cause of secondary adrenocortical insufficiency and accompaniment with primary empty sella has been reported in several cases. We present a case of isolated ACTH deficiency associated with empty sella. A sixty-two year old woman was admitted to our endocrine clinic with complaints of weakness, fatigue, weight loss, nausea, vomiting, and lack of appetite for about one month. Physical examination indicated orthostatic hypotension and epigastric tenderness. Laboratory investigations revealed hypoglycemia, hyponatremia and anemia, in addition low plasma cortisole and ACTH levels. Serum cortisole responses to short and prolonged ACTH stimulation were tested and partial and accurate responses were obtained, respectively. Plasma ACTH and serum cortisole levels failed to respond after intravenous injection of human corticotropin releasing hormone. Other hypophysial hormone levels were within the normal reference ranges. Although cranial and abdominal computerized tomography images were evaluated as normal, cranial magnetic resonance imaging of the pituitary gland revealed 'primary empty sella turcica'. Replacement therapy with methylprednisolon resulted in the improvement of hypoglycemia, hyponatremia and clinical symptoms. Based on these results, the patient was diagnosed as isolated ACTH deficiency and was scheduled for follow up by our outpatient clinic. Our report is consistent with other reports pointing out that primary empty sella may be responsible for pathogenesis of isolated ACTH deficiency....

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Journal Article 2007; 28(6): 757-760 PubMed PMID: 18063930 Citation  Keywords:  Activity Cycles:physiology, Aging:immunology, Animals, Columbidae, Leukocytes:physiology, Melatonin:physiology, Neuroimmunomodulation:physiology, Phagocytosis:physiology, Serotonin:blood, Sleep:physiology, Superoxides:blood, Tryptophan:physiology, Wakeful.   

: All organisms present circadian rhythm in most of their physiological functions, and among them there stand out sleep, motor activity, immune function, the secretion of melatonin, and the production and release of numerous neurotransmitters, in particular of serotonin because of its relationship with the aforementioned factors. Aging changes these rhythms, altering sleep quality and contributing to immunosenescence. Treatment with exogenously administered melatonin or tryptophan may restore these impaired functions due to aging. In our animal model (Streptopelia risoria), both the hormone and the amino acid acted on the activity-rest rhythms, modulating the circulating levels of melatonin and serotonin, and increased the cell viability and resistance to induced oxidative stress of blood heterophils, at the same time as enhancing the phagocytic function and neutralizing the superoxide anions deriving from this immune function. Also, in the old individuals, the treatments with melatonin and tryptophan at the concentrations and times of administration considered suitable improved nocturnal rest besides reverting the immunosuppressory and oxidative effects accompanying phagocytosis at these advanced ages....

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