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M Relja

Publications and source records attributed to M Relja.

At least 19 recordsLinked to original sources
PubMed2006

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study.

Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.

Adult↗
PubMed2006

Safety and efficacy of botulinum toxin type A following long-term use.

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.

Animals↗
PubMed2005

Botulinum toxin type A in experimental neuropathic pain.

A peripheral application of botulinum toxin type A (7 U/kg) has significantly reduced thermal and mechanical hypersensitivity in rats with the partial sciatic nerve transection as a classical model of surgical neuropathy.

Animals↗
PubMed2000

No evidence for a parent-of-origin effect detected in the pattern of inheritance of schizophrenia.

BACKGROUND: Schizophrenia is a complex genetic disorder with no clear pattern of inheritance. Epigenetic modification of genes may thus play a role in its transmission. METHODS: In our study, 439 families with at least two ill siblings with schizophrenia (208 with unilineal transmission) were examined for evidence of a parent-of-origin effect (e.g., evidence of parental imprinting on the familial transmission of schizophrenia). RESULTS: No significant difference in the prevalence of maternal compared with paternal transmission was found. In addition, affected male subjects did not differ from affected female subjects in the proportion of their offspring diagnosed with schizophrenia. CONCLUSIONS: Although the transmission of schizophrenia may be influenced by epigenetic events, our study fails to find evidence that one epigenetic mechanism, a parent-of-origin imprinting effect, determines whether an individual expresses the illness.

Adult↗
PubMed2000

Genotyping of CYP2D6 in Parkinson's disease.

Parkinson's disease is characterized by progressive degradation of dopaminergic neurons. Cytochrome P450 CYP2D6 enzyme is one of the most investigated and highly polymorphic isoforms, which metabolizes many drugs and is also involved in the metabolism of dopamine. Using allele-specific multiplex PCR, we genotyped 186 subjects for CYP2D6 *3, *4, *6, *7, and *8 alleles in order to estimate allelic, genotype and predicted phenotype frequencies in the control and patient groups, and to investigate the possible statistical difference between Parkinson's disease patients (n=41) and healthy controls (n=145). Parkinson's disease patients were further divided into two subgroups according to Hoehn and Yahr staging of the disease (HY), i.e. groups with HY stage less than 2.5 (HY <2.5; n=27) and more than 2.5 (HY >2.5; n=14). A subgroup of Parkinson's disease patients exhibiting side effects such as "on-off" phenomenon and dyskinesia (both suggesting favorable response to therapy) were compared with a subgroup of patients showing no such response. The preliminary results of this study showed that only the prevalence of CYP2D6 *4 allele differed significantly between the PD patients and control group (20.7% vs. 11.0%; p=0.027; RR=2.1, 95%CI 1.113-3.994). In the HY >2.5 subgroup, the CYP2D6*4 allelic difference was even greater (25.0% vs. 11.0% in controls; p=0.062, RR=2.69, 95%CI 1.090-6.624). Genotype frequencies differed only in the HY >2.5 subgroup, however with a level of significance of p=0.095.

Adult↗
PubMed1998

Neuronal histamine deficit in Alzheimer's disease.

Histamine is known to be a neurotransmitter in the brain, but it has not been clearly implicated in major diseases. All histaminergic neurons reside in the posterior hypothalamus and innervate most brain areas, which is compatible with the concept that histamine is involved in general central regulatory mechanisms. A sensitive high-performance liquid chromatographic fluorimetric method was used to measure histamine contents in post mortem Alzheimer brains and age-matched controls. The cellular storage sites and distribution of histaminergic nerve fibers were examined with a specific immunohistochemical method. The histamine content was significantly reduced in the hypothalamus (42% of control value), hippocampus (43%) and temporal cortex (53%) of Alzheimer brains. Differences in other cortical areas, putamen and substantia nigra were not significant. Histamine-containing nerve fibers were found in the hippocampus, parahippocampal gyrus and subiculum of both Alzheimer brains and controls. No histamine-containing mast cells were seen in these temporal structures. Histamine in the human temporal lobe is stored in nerve fibers originating from the posterior hypothalamus, and not in mast cells. Decrease in brain histamine may contribute to the cognitive decline in Alzheimer's disease directly or through the cholinergic system. Development of drugs that penetrate the blood brain barrier and increase histaminergic activity might be beneficial in Alzheimer's disease.

Aged↗
PubMed1990

Effect of long-lasting diabetes mellitus on rat and human brain monoamines.

Experimental alloxan- or streptozotocin-produced diabetes in rats was accompanied by an increase in the levels of norepinephrine, dopamine, and serotonin, whereas the contents of metabolites, i.e., 5-hydroxyindoleacetic acid and homovanillic acid, in the whole brain gradually decreased with the duration of diabetes. Among the striatum, thalamus, and hypothalamus of alloxan diabetic rats, monoamine alterations were observed only in the hypothalamus; after 1 week an increase of norepinephrine content and after 13 weeks an increase of norepinephrine and dopamine contents were found. Tissues of 11 brain regions of 10 diabetic and 12 control patients post mortem were investigated for monoamine concentrations. Patients were all male, of similar age and interval between death and autopsy. Diabetic patients had an increase in the content of serotonin in the medial and lateral hypothalamus. The content of dopamine increased in the medial hypothalamus, putamen, and medial and lateral pallidus. In diabetic patients, the content of norepinephrine increased in the lateral pallidus and decreased in the nucleus accumbens and claustrum. Thus, it seems that diabetes mellitus in rats, as well as in humans is associated with regionally specific changes in brain monoamines.

Aged↗
PubMed1990

[Hepatolenticular degeneration].

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.

Adolescent↗
PubMed1988

Serotonin and norepinephrine in the spinal cord of man.

The content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) was analysed in 71 human spinal cords obtained post-mortem. The highest content of 5-HT, 5-HIAA and NE was found in the lumbar enlargement of the spinal cord. 5-HT and 5-HIAA content increased from fetal to adult spinal cord whereas the content of NE decreased. Characteristic segmental distribution of measured monoamines was present in adult spinal cord only. In two patients spinal cord lesion led to the reduction in spinal cord content of 5-HT, 5-HIAA and NE and loss of characteristic segmental distribution of these substances. These results are in general agreement with observations on spinal cord of different animal species.

Adult↗
PubMed1983

Evidence for a widely distributed peripheral dopaminergic system.

The hypothesis presented in this paper is that dopamine (DA) is a widely distributed neurotransmitter and/or cotransmitter in the autonomic nervous system. This hypothesis is based on the following evidence. Morphologically, DA-containing neurons have been demonstrated in autonomic ganglia, and dopaminergic axons have been identified in kidney and canine paw pad. On the basis of pharmacological experiments, the existence of dopaminergic nerves was suggested in vas deferens, stomach, and mesenteric artery. Biochemically, we found intensive catabolism of DA in different peripheral tissues of the rat and human. Furthermore, dopaminergic receptors have a widespread distribution in the body, and a high concentration of DA occurs in plasma with only some originating from the adrenal gland. The concentration of plasma DA closely reflects the activity of the autonomic nervous system. These observations together with our finding of relatively high concentrations of DA and its metabolites in several peripheral nerves suggest the possibility of a widely distributed peripheral dopaminergic system.

Animals↗
PubMed1982

Evidence for the presence of dopaminergic receptors in vas deferens.

Specific dopaminergic recognition sites were identified in membranes prepared from rat vas deferens with the ligand (3H)-haloperidol. Specific binding, defined as the difference of (3H)-haloperidol binding in the presence or absence of an excess of unlabelled haloperidol (100 microM), was saturable and a Scatchard analysis of the data revealed a Kd = 21 nM and a Bmax = 74 fmol/mg prot. (+)-Butaclamol was several times more active in displacing (3H)-haloperidol from binding sites than its pharmacologically inactive enantiomer, (-)-butaclamol, demonstrating stereospecificity of binding. Dopamine displaced 50% of (3H)-haloperidol binding at a concentration of approximately 10 microM, while norepinephrine, epinephrine and serotonin were practically ineffective at this concentration. Our results support the notion that there are dopaminergic receptors in the rat vas deferens. We speculate that some of the known effects of dopamine and dopaminergic drugs on sexual behavior may be mediated peripherally and not solely via the CNS as is usually assumed.

Animals↗
PubMed1982

Catabolism of endogenous dopamine in peripheral tissues: is there an independent role for dopamine in peripheral neurotransmission?

Dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), have been measured in peripheral tissues of the rat and human by gas chromatography-mass spectrometry. The content of HVA and DOPAC in peripheral tissue is higher than in blood and is usually higher than the content of DA. In the rat, chemical denervation with 6-hydroxydopamine decreased the tissue content of DOPAC. Inhibition of monoamine oxidase increased tissue DA. Apparently, in vivo, a large quantity of peripheral DA is catabolized rather than converted to norepinephrine (NE). These observations suggest that either NE synthesis is inefficient, with a large quantity of DA wasted and not converted to NE, or that DA is physiologically utilized as a neurotransmitter and/or cotransmitter in many peripheral nerves. A survey of the reported actions of DA on peripheral tissues suggests that the latter proposal is more likely.

3,4-Dihydroxyphenylacetic Acid↗