GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats.

Treatment of tremors, such as in essential tremor (ET) and Parkinson's disease (PD) is mostly ineffective. Exact tremor pathomechanisms are unknown and relevant animal models are missing. GABA-A receptor is a target for tremorolytic medications, but current non-selective drugs produce side effects and have safety liabilities.

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models.

Essential tremor (ET) is one of the most common neurological disorders that often affects people in the prime of their lives, leading to a significant reduction in their quality of life, gradually making them unable to independently perform the simplest activities. Here we show that current ET pharmacotherapy often does not sufficiently alleviate disease symptoms and is completely ineffective in more than 30% of patients. At present, deep brain stimulation of the motor thalamus is the most effective ET treatment.

Blockade of adenosine A receptors inhibits Tremulous Jaw Movements as well as expression of zif-268 and GAD65 mRNAs in brain motor structures.

Tremor is one of the motor symptoms of Parkinson's disease (PD), present also in neuroleptic-induced parkinsonism. Tremulous Jaw Movements (TJMs) are suggested to be a well-validated rodent model of PD resting tremor. TJMs can be induced by typical antipsychotics and are known to be reduced by different drugs, including adenosine A receptor antagonists.

Potential antipsychotic action of the selective agonist of adenosine A1 receptors, 5'-Cl-5'-deoxy-ENBA, in amphetamine and MK-801 rat models.

Background: Disturbances of dopaminergic and glutamatergic transmissions have been suggested to be involved in the pathomechanisms underlying psychotic symptoms of schizophrenia. In line with this concept, hyperlocomotion induced by the dopaminomimetic amphetamine and the uncompetitive antagonist of NMDA receptors MK-801 (dizocilpine) in rodents is a generally established model for screening of new potential antipsychotic drugs. Since recent studies have indicated that receptors for adenosine may be targets for antipsychotic therapy, the aim of the present study was to investigate an influence of 5'-Cl-5'-deoxy-ENBA, a potent and selective adenosine A receptor agonist, on hyperlocomotion induced by amphetamine and MK-801.

Pramipexole Reduces zif-268 mRNA Expression in Brain Structures involved in the Generation of Harmaline-Induced Tremor.

Essential tremor is one of the most common neurological disorders, however, it is not sufficiently controlled with currently available pharmacotherapy. Our recent study has shown that pramipexole, a drug efficient in inhibiting parkinsonian tremor, reduced the harmaline-induced tremor in rats, generally accepted to be a model of essential tremor. The aim of the present study was to investigate brain targets for the tremorolytic effect of pramipexole by determination of the early activity-dependent gene zif-268 mRNA expression.

Inhibition of Excessive Glutamatergic Transmission in the Ventral Thalamic Nuclei by a Selective Adenosine A1 Receptor Agonist, 5'-Chloro-5'-Deoxy-(±)-ENBA Underlies its Tremorolytic Effect in the Harmaline-Induced Model of Essential Tremor.

The primary cause of harmaline tremor, which is a model of essential tremor (ET) in animals, is excessive activation of olivocerebellar glutamatergic climbing fibers. Our recent study indicated that 5'-chloro-5'-deoxy-(±)-N6-(±)-(endo-norborn-2-yl)adenosine (5'Cl5'd-(±)-ENBA), a potent and selective adenosine A1 receptor (A1) agonist, inhibited harmaline tremor. The present study was aimed to evaluate the role of glutamatergic transmission system in 5'Cl5'd-(±)-ENBA tremorolytic action in the harmaline model in rats, by analyzing glutamate release in the motor nuclei of the thalamus and mRNA expression of glutamatergic neuron markers (vGlut1/2) in reference to the general neuronal activity marker (zif-268) in different brain structures.

Tremorolytic effect of 5'-chloro-5'-deoxy-(±)-ENBA, a potent and selective adenosine A1 receptor agonist, evaluated in the harmaline-induced model in rats.

Aim: The aim of this study was to examine the role of adenosine A receptors in the harmaline-induced tremor in rats using 5'-chloro-5'-deoxy-(±)-ENBA (5'Cl5'd-(±)-ENBA), a brain-penetrant, potent, and selective adenosine A receptor agonist.

Methods: Harmaline was injected at a dose of 15 mg/kg ip and tremor was measured automatically in force-plate actimeters by an increased averaged power in the frequency band of 9-15 Hz (AP2) and by tremor index (a difference in power between AP2 and averaged power in the frequency band of 0-8 Hz). The zif-268 mRNA expression was additionally analyzed by in situ hybridization in several brain structures.

Adaptive down-regulation of the serotonin transporter in the 6-hydroxydopamine-induced rat model of preclinical stages of Parkinson's disease and after chronic pramipexole treatment.

Our recent study has indicated that a moderate lesion induced by bilateral 6-hydroxydopamine (6-OHDA) injections into the ventrolateral region of the caudate-putamen (CP) in rats, modeling preclinical stages of Parkinson's disease, induces a "depressive-like" behavior which is reversed by chronic treatment with pramipexole (PRA). The aim of the present study was to examine the influence of the above lesion and chronic PRA treatment on binding to the serotonin transporter (SERT) in different brain regions. As before, 6-OHDA (15 μg/2.

Pramipexole at a Low Dose Induces Beneficial Effect in the Harmaline-induced Model of Essential Tremor in Rats.

Aims: The aim of the study was to examine the effects of preferential agonists of dopamine D3 receptors: pramipexole and 7-OH-DPAT on the harmaline-induced tremor in rats (a model of essential tremor, ET). To study receptor mechanisms of these drugs, rats were pretreated with dopamine D3 receptor antagonists--SB-277011-A and SR-21502, an antagonist of presynaptic D2/D3 receptors--amisulpride, or a nonselective antagonist of D2-like receptors, haloperidol, at a postsynaptic dose.

Methods: For tremor measurement, fully automated force plate actimeters were used and data were analyzed using fast Fourier transform.

Apomorphine enhances harmaline-induced tremor in rats.

Background: Harmaline-induced tremor is a well-known model of essential tremor in humans. The aim of the present study was to examine the influence of apomorphine, a non-selective dopamine receptor agonist, on the tremor induced by harmaline in rats. Propranolol (a first-line drug in essential tremor) was used as a reference compound.

Alterations of BDNF and trkB mRNA expression in the 6-hydroxydopamine-induced model of preclinical stages of Parkinson's disease: an influence of chronic pramipexole in rats.

Our recent study has indicated that a moderate lesion of the mesostriatal and mesolimbic pathways in rats, modelling preclinical stages of Parkinson's disease, induces a depressive-like behaviour which is reversed by chronic treatment with pramipexole. The purpose of the present study was to examine the role of brain derived neurotrophic factor (BDNF) signalling in the aforementioned model of depression. Therefore, we investigated the influence of 6-hydoxydopamine (6-OHDA) administration into the ventral region of the caudate-putamen on mRNA levels of BDNF and tropomyosin-related kinase B (trkB) receptor.

FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group.

Gonadotropin (LH, FSH) levels in serum and cyst fluid in epithelial tumors of the ovary.

Objectives: The aim of this work was to determine gonadotropin (LH, FSH) levels in serum and cyst fluid in various type of ovarian epithelial neoplasms (benign, borderline, malignant) and to compare them with levels in benign cysts. Additionally we decided to estimate if there were some significant correlations between serum and ovarian cyst fluid in gonadotropin levels in all investigated groups.

Materials And Methods: The study group included 74 patients before (n=36) and after (n=38) menopause, divided into four groups depending on the histopathologic diagnosis.

Leptin, neuropeptide Y, beta-endorphin, gonadotropin, and estradiol levels in girls before menarche.

More than two decades of clinical studies have provided us with the opportunity to develop and implement criteria that distinguish three phases during pre-menarche, paralleling rising levels of estrogens, namely 'pre-estrogenization', 'onset of estrogenization' and 'full estrogenization'. The aim of this study was to examine the relationships between somatic features and levels of leptin, neuropeptide Y (NPY), beta-endorphin, gonadotropin and estradiol in pubertal girls before menarche. Weight, height, body mass index (BMI), tertiary sex features, estrogen-related changes in hymen, fat and lean body mass were studied on a quarterly basis in 45 girls.

[Age at menarche and the investigation of selected biophysical parameters in the course of menarche].

Design: The aim of our study was a currently clinical analysis of menarche.

Materials And Methods: The mean age of menarche was investigated in 4497 girls between 1975-1997 69 girls were examined throughly in the course of menarche. Age at menarche, body weight, height, body mass index (BMI), some of the hormones and ultrasonography of sexual organs were investigated.

[The levels of selected hormones in serum and ovarian cyst fluid in girls and young women].

Objectives: The aim of the study was to determinate levels of the FSH, LH and E2 in serum and ovarian cyst fluid in neoplastic tumors (7 benign, 1 of low malignant potential) and functional cysts.

Material And Methods: We measured the concentrations of the FSH, LH and E2 at 12 girls and young women hospitalized in our teaching department using immunoenzymatic method.

Results: We found higher levels of gonadotropins in serum and particular in ovarian cyst fluid at neoplastic tumors in comparison with functional cysts.

[The comparison of CA-125 and CEA levels in serum and ovarian cyst fluid in girls and young women].

Objectives: The aim of the study was to compare the CA-125 and CEA levels in serum and ovarian cyst fluid.

Materials And Methods: Concentration of the CA-125 and CEA were measured at 12 girls and young women with benign, low malignant potential and functional cysts hospitalized in our teaching department. Concentrations were measured using immunoenzymatic method.

[Most common neoplasms of female genital organs and hypo-thalamic-hypophysial-ovarian regulation in the postmenopausal period].

Levels of FSH, LH and E2 were evaluated by means of EIA methods in 62 post-menopausal women qualified for operation treatment. In 46 cases neoplasms of uterus body and in 16 cases neoplasms of uterus cervix and an ovary were stated. Higher level of estradiol and lower levels of gonadotrophins were shown in cases with uterus body neoplasms and opposite, lower estradiol levels and higher gonadotrophins values in cases with cervix and ovarian neoplasms.

[Ultrasonography, laparoscopy, neoplastic markers--new possibilities of conservative operative treatment for ovarian neoplasms in girls and young women].

The knowledge of ovarian physiopathology and the employing of modern diagnostic methods (ultrasonography, laparoscopy) allow to avoid to operate patients with functional cysts. Girls and young women should be evaluated individually for ovarian surgical procedures. The operative treatment should be so conservative as possible employing all diagnostic and monitoring methods including specific markers assays.

[Behavior of SCC antigen in girls with a high risk of developing cervical carcinoma].

The work presents the results of studies on level of SCC antigen in 28 patients of 14 girls, sexual clinical active with cervical erosion type II, among which in 10 cases HPV virus were founded. The second group consists of 14 women from normal environments, treated for CIN. The antigen SCC was determined in patients blood serum by immunoenzymatic method.

[Activity of b-endorphin in patients with premature ovarian failure].

Examination of B-endorphin blood serum levels of 27 girls and young women with premature ovarian function depression was performed Patients were not pregnant before. The 54 young, regularly menstruating, healthy women composed the control group, who were divided into two groups according to the menstrual phase. Levels of B-endorphin were lower in examined group than in control one.

[Behavior of SCC marker level in cervix erosion, cervix dysplasia and cervical pre-invasive carcinoma].

The work presents the results of studies on the behaviour of SCC antigen in 52 patients aged 21-70 years, with pathologic changes involving the uterine cervix and classified to the groups of erosion, dysplasia and carcinoma in different stage of advancement. The SCC antigen was determined in patients blood sera by radioimmunologic method, on the basis of Abbott Firm testes. An increase in concentration was observed exceed the norm (2 ng/ml) in cases of CIN and CIS.