Search NEL Online

Journal Article 2009; 30(2): 268-274 PubMed PMID: 19675520 Citation  Keywords:  Animals, Antineoplastic Agents, Hormonal:pharmacology, Apoptosis:drug effects, Cell Line, Tumor, Cell Proliferation:drug effects, Cell Survival:drug effects, Estradiol:analogs & derivatives, Estrogen Antagonists:pharmacology, MAP Kinase Kinase 4:metabolis.   

OBJECTIVES: Unlike the successful endocrine therapy of breast cancers and other estrogen-dependent diseases, little is known about the effect of anti-estrogen treatment on pituitary tumors. Our objectives were to study the effect of fulvestrant, a new type anti-estrogen devoid of any agonistic activities, on prolactinoma cell line MMQ in vitro and its possible mechanisms.

DESIGN: In the experiment, the prolactin concentration, proliferation and apoptosis of the MMQ cell were measured to investigate the anti-tumor effect of the fulvestrant. The expression of estrogen receptor (ESR) mRNA and protein and MAPK pathway-related proteins ERK1 and 2, JNK, and p38 were measured to investigate the possible mechanisms.

RESULTS: Fulvestrant significantly inhibited prolactin secretion (up to 85.5%), decreased proliferation (IC50 = 32.4 nmol/l), and promoted apoptosis of the MMQ cells.

CONCLUSIONS: The suppression was possibly mediated by inhibition of ESR mRNA expression, down-regulation of ESR expression and activation of MAPK pathway-related proteins. Thus, fulvestrant has suppressive effects on prolactinoma cells and its anti-tumor mechanism appears to be related to the inhibition of ESR and the MAPK pathway....

Read abstract  Full text PDF

Journal Article 2009; 30(2): 153-179 PubMed PMID: 19675519 Citation  Keywords:  Animals, Behavior:physiology, Bone and Bones:metabolism, Cannabinoid Receptor Modulators:antagonists & inhibitors, Cardiovascular System:metabolism, Endocannabinoids, Gastrointestinal Tract:metabolism, Humans, Immune System:metabolism, Neoplasms:metabolis.   

: The endocannabinoid system (ECS) is a lipid signalling system, comprising of the endogenous cannabis-like ligands (endocannabinoids) anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which derive from arachidonic acid. These bind to a family of G-protein-coupled receptors, called CB1 and CB2. The cannabinoid receptor 1 (CB1R) is distributed in brain areas associated with motor control, emotional responses, motivated behaviour and energy homeostasis. In the periphery, the same receptor is expressed in the adipose tissue, pancreas, liver, GI tract, skeletal muscles, heart and the reproduction system. The CB2R is mainly expressed in the immune system regulating its functions. Endocannabinoids are synthesized and released upon demand in a receptor-dependent way. They act as retrograde signalling messengers in GABAergic and glutamatergic synapses and as modulators of postsynaptic transmission, interacting with other neurotransmitters. Endocannabinoids are transported into cells by a specific uptake system and degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS is involved in various pathophysiological conditions in central and peripheral tissues. It is implicated in the hormonal regulation of food intake, cardiovascular, gastrointestinal, immune, behavioral, antiproliferative and mammalian reproduction functions. Recent advances have correlated the ECS with drug addiction and alcoholism. The growing number of preclinical and clinical data on ECS modulators is bound to result in novel therapeutic approaches for a number of diseases currently treated inadequately. The ECS dysregulation has been correlated to obesity and metabolic syndrome pathogenesis. Rimonabant is the first CB1 blocker launched to treat cardiometabolic risk factors in obese and overweight patients. Phase III clinical trials showed the drug's ability to regulate intra-abdominal fat tissue levels, lipidemic, glycemic and inflammatory parameters. However, safety conerns have led to its withrawal. The role of endocannabinoids in mammalian reproduction is an emerging research area given their implication in fertilization, preimplantation embryo and spermatogenesis. The relevant preclinical data on endocannabinoid signalling open up new perspectives as a target to improve infertility and reproductive health in humans....

Read abstract  Full text PDF

Case Reports 2009; 30(2): 192-194 PubMed PMID: 19675518 Citation  Keywords:  Cesarean Section, Female, Fibroma:complications, Humans, Meigs Syndrome:complications, Ovarian Neoplasms:complications, Pregnancy, Pregnancy Complications, Neoplastic:pathology, Pregnancy Outcome, Virilism:etiology, Young Adult,.   

BACKGROUND: A half of virilizing ovarian tumors in pregnancy are malignant. The risk of cancer increases with ascites and hydrothorax. Our case shows that such tumor can be benign with good outcome.

CASE: Primigravida in 30 weeks with advanced hirsutism (from 15 weeks), vomiting, epigastric pain, dyspnoea, ascites, hydrothorax, ovarian mass and high level of serum testosterone was operated. After the tumorectomy (fibrothecoma) we performed cesarean section (placental abruption suspected). The female fetus had no signs of virilization. In mother all symptoms and effusions resolved.

CONCLUSION: Meigs' syndrome in pregnancy leads to acute clinical symptoms and needs the surgical intervention with the risk of placental abruption. Virilization of mother was the first symptom of ovarian tumor but the female fetus was protected of hyperandrogenism....

Read abstract  Full text PDF

Journal Article 2009; 30(2): 237-244 PubMed PMID: 19675517 Citation  Keywords:  Analysis of Variance, Blood Pressure, Bulimia Nervosa:physiopathology, Cold Temperature, Dietary Sucrose:administration & dosage, Eating:physiology, Female, Heart Rate, Humans, Pain:physiopathology, Pain Threshold, Perception:physiology, Rest:physiology, .   

OBJECTIVES: To investigate if the increased pain threshold in women with bulimia nervosa (BN) may be due to chronic stress-induced analgesia.

METHODS: We measured thermal pain threshold latency, blood pressure and heart rate in 21 women with BN and 21 healthy women (HW) under six consecutive conditions: rest I, mental arithmetic task, rest II, eating sweet food, rest III, cold-pressor test.

RESULTS: Thermal pain threshold latency was longer in BN than in HW in all six conditions. It increased during mental arithmetic test and remained increased during the rest of the experiment in both groups. In the BN group, the increase of pain threshold during mental arithmetic was positively correlated with illness duration. The differential modulation of pain threshold by stress in BN and HW could not be explained by autonomic system reactivity. In HW, the pain threshold increased more during eating and blood pressure increased more during mental stress; in BN, the pain threshold was highest in the mental stress condition and blood pressure was most increased during eating. During the cold pressor test, women with BN showed smaller blood pressure increase and tolerated the cold for shorter time than HW.

CONCLUSION: The observed marked modulation of pain threshold by experimental stress suggests that stress-induced analgesia is unlikely to account for baseline pain insensitivity in BN. Increased pain threshold in BN is a stable yet incompletely understood phenomenon, which may be related to the predisposition to or maintenance of the disorder....

Read abstract  Full text PDF

Journal Article 2009; 30(2): 227-236 PubMed PMID: 19675516 Citation  Keywords:  Adult, Analysis of Variance, Blood Proteins:analysis, Chromatography, High Pressure Liquid, Emotions:physiology, Female, Fibrinogen:metabolism, Humans, Interpersonal Relations, Male, Mass Spectrometry, Serum Albumin:metabolism, Sexual Behavior:physiology,.   

OBJECTIVES: Warm physical contact may positively influence our health and well-being; however, it has not been investigated yet whether serum proteins are influenced by warm physical contact in healthy couples. In this study, we focused on psychological and physiological effects of warm partner contact in healthy couples.

METHODS: When participants freely kissed and hugged their romantic partners, they were asked to subjectively evaluate their present emotions. Furthermore, changes of serum proteins were determined by using ProteinChip surface enhanced laser desorption/ionization-time-of-flight-mass spectrometry (SELDI-TOF-MS). We characterized these proteins by using biochemical techniques combined with gel filtration high performance liquid chromatography (HPLC), reverse-phase HPLC, and sequencing analyses.

RESULTS: Romantic couples became happier and less irritated after kissing and hugging. Accompanying these psychological changes, SELDI-TOF-MS indicated that the intensities of 66-k Da, 11.7-k Da, and 5.9-k Da serum proteins were increased. These proteins were identified as serum albumin and beta2-microglobulin, and probably fibrinogen fragment. The feeling of happiness positively correlated and the feeling of irritation negatively correlated with intensities of serum albumin and beta2-microglobulin.

CONCLUSION: These results suggest that psychological stress may be reduced and we may feel happiness when we kiss and hug a romantic partner. Furthermore, these results also suggest that warm partner contact influences peripheral circulating proteins, more importantly, may promote health and well-being....

Read abstract  Full text PDF

Journal Article 2009; 30(2): 209-214 PubMed PMID: 19675515 Citation  Keywords:  Aged, Aged, 80 and over, Amiodarone:adverse effects, Female, Follow-Up Studies, Goiter:radiotherapy, Humans, Hypothyroidism:chemically induced, Iodine Radioisotopes:adverse effects, Male, Middle Aged, Recurrence, Remission Induction, Thyrotoxicosis:chemic.   

INTRODUCTION: Amiodarone (AM) is frequently used in the therapy of patients with cardiac disorders. However, due to high iodine content, it has side effects on thyroid function. The use of radioiodine therapy (RIT) in amiodarone-induced thyrotoxicosis (AIT) with low radioactive iodine uptake (RAIU) is still controversial. In these patients therapeutic choices for refractory disease include surgery, antithyroid drugs, or glu ocorticosteriods.

AIM: The aim of the study was to evaluate the efficacy of RIT in patients presenting AIT and low RAIU in two-year follow-up.

PATIENTS AND METHODS: 40 patients (25 men and 15 women) aged from 63 to 83 years (x +/- SD: 66.2 +/- 5.0 years; median: 65 years) treated with RIT were included into the study. In these patients AM therapy was essential for the underlying heart disorder, while surgery, antithyroid drugs or glucocorticosteroids, were contraindicated. Forty seven patients with toxic multinodular goiter (TMNG) (39 women and 8 men), matched for age (67 +/- 12 yr; range 54-89 yr), were enrolled into the study as a comparative group. The diagnostic procedures included baseline thyroid function tests (thyrothropin - TSH, free triiodothyronine - fT3 and free thyroxine - fT4 levels), thyroid autoantibodies measurement (antithyroglobulin autoantibodies - TgAb, antithyroid peroxidase autoantibodies - TPOAb, anti-TSH receptor autoantibodies - TRAb), thyroid ultrasonography, thyroid scintiscan and RAIU assessment.

RESULTS: Serum values of TSH, TgAb, TPOAb and TRAb were undetectable in both groups. In patients with AIT fT4 level was 18.7 to 38.7 pmol/l (mean: 27.1 +/- 5.8) and fT3 concentration was 3.9 to 5.6 pmo/l (mean: 5.7 +/- 1.4), while in TMNG patients level of fT4 was 31.5 to 22.2 pmol/l (mean: 25,3 +/- 5,8) and fT3 concentration was 3.8 to 4,2 pmo/l (mean: 4,2 +/- 0,2). Mean RAIU values after 5h and 24h in AIT patients were 2.3 +/- 0.5 and 3.1 +/- 0.9%, while in TMNG patients were 18,0 +/- 3,8 and 35,7 +/- 9,1%, respectively. A significant difference (p<0.001) between 5h and 24h RAIU in AIT compared to TMNG was noted. In all patients with AIT, a dose of 800 MBq of 131I was administered. During two-year-observation recurrence of hyperthyroidism was observed in two patients (5%) with TMNG. These patients received a second radioiodine dose 16.2 +/- 15 months later (the mean re-treatment dose was 735.93 +/- 196.1 MBq). In comparison, none of the patients with AIT required a second 131I dose and only one patient (2.5%) 6 months after ablative 131I dose needed anti-thyroid medication. Transient hypothyroidism was observed in only two patients (5%) with AIH, though was not observed in TMNG. During follow-up time, no sudden deaths in AIT patients were observed; one patient was diagnosed with prostate cancer, and in one patient acute toxic hepatitis after AM occurred.

CONCLUSION: RIT may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated....

Read abstract  Full text PDF

Journal Article 2009; 30(2): 245-255 PubMed PMID: 19675514 Citation  Keywords:  Acromegaly:blood, Acylation, Adult, Aged, Blood Glucose:metabolism, Cholesterol:blood, Female, Ghrelin:blood, Growth Hormone:blood, Humans, Hypercholesterolemia:blood, Hyperglycemia:blood, Hyperinsulinism:blood, Insulin:blood, Insulin-Like Growth Factor I.   

UNLABELLED: It is unknown if altered ghrelin secretion might contribute to the development of metabolic complications in acromegaly. The AIM OF THE STUDY was to: 1) assess if serum concentrations of total and acylated ghrelin in patients with acromegaly differ in the presence of various metabolic complications (hypercholesterolemia, hyperinsulinemia, hyperglicemia). 2) assess the correlations between concentrations of ghrelin and concentrations of GH, IGF-1, cholesterol, insulin and glucose in patients with acromegaly.

MATERIALS: 24 patients with previously diagnosed acromegaly (11 subjects with active and 13 subjects with inactive disease) and 12 healthy subjects. 23 subjects were treated in the past with neurosurgery, 3 subjects with radiotherapy. 7 patients were receiving octreotide LAR at the time of the study.

METHODS: In all studied subjects the concentrations of total ghrelin, acylated ghrelin, GH, IGF-1, insulin, glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglicerydes, were measured.

RESULTS: The concentrations of total and acylated ghrelin did not significantly differ between patients with active and inactive disease. The mean concentrations of total and acylated ghrelin were significantly higher in acromegalic patients who presented with hypercholesterolemia compared with patients with normocholesterolemia. In patients with hypercholesterolemia the ratio of acylated/total ghrelin was 16%. In patients with active acromegaly there was a statistically significant positive correlation between the concentration of total ghrelin and the concentration of total cholesterol and LDL cholesterol. There was also a positive correlation between the concentration of acylated ghrelin and LDL cholesterol (without statistical significance). In patients with inactive acromegaly there was a statistically significant positive correlation between the concentration of acylated ghrelin and the concentration of triglycerides and a positive correlation between total ghrelin and triglycerides, but statistically insignificant. There were no differences in ghrelin levels depending on the insulin and glucose concentrations.

CONCLUSIONS: Some metabolic complications of the disease might result not only from GH hypersecretion but also from altered ghrelin secretion....

Read abstract  Full text PDF

Journal Article 2009; 30(2): 215-220 PubMed PMID: 19675513 Citation  Keywords:  Acetic Acid, Adrenergic alpha-Agonists:pharmacology, Analgesics, Non-Narcotic:pharmacology, Analysis of Variance, Animals, Dose-Response Relationship, Drug, Drug Synergism, Ibuprofen:pharmacology, Male, Mice, Motor Activity:drug effects, Oxazoles:pharmaco.   

OBJECTIVES: The aim of the study was to ascertain whether rilmenidine, a second generation imidazoline-alpha-2-adrenoreceptor agonist, is able to increase analgesic effects of ibuprofen in the writhing test in mice. Experimental studies combining these agents have not yet been published.

METHODS: An acetic acid (0.7%) solution was injected into the peritoneal cavity and the number of writhes was counted. The influence on locomotor performance was tested using the rotarod test.

RESULTS: Rilmenidine, ibuprofen, and rilmenidine-ibuprofen fixed-ratio combinations produced dose-dependent antinociceptive effects. ED50 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical additive ED50 value for the rilmenidine-ibuprofen combination was 34.00 +/- 9.39 mg/kg. This value was significantly greater than the observed ED50 value which was 18.07 +/- 5.41 mg/kg, indicating a synergistic interaction. Rilmenidine did not impair motor coordination, as measured by the rotarod test, at antinociceptive and higher doses.

CONCLUSIONS: The present results suggest that rilmenidine enhances the analgesic activity of ibuprofen. If rilmenidine produces antinociception in humans, then the synergistic antinociception of rilmenidine with ibuprofen could offer therapeutic advantage for clinical treatment of pain....

Read abstract  Full text PDF