Immunohistochemical analysis of MMP-9 and COX-2 expression in carotid atherosclerotic plaques among patients undergoing carotid endarterectomy: A prospective study.

Background: Matrix metalloproteinase-9 protein (MMP-9) and cyclooxygenase-2 (COX-2) proteins may have a role in remodelling of atherosclerotic plaques. We analysed and compared the radiological, histological and immunohistochemical characteristics of carotid atherosclerotic plaques between symptomatic and asymptomatic patients who underwent carotid endarterectomy (CEA).

Methods: This prospective single-blinded study included 31 patients (70 [64-75] years, 58% males, 42% symptomatic) who underwent CEA and a total of 155 carotid plaque sections that were analysed.

The role of magnetic resonance imaging and the expression of MMP-9 protein in the analysis of carotid atherosclerotic plaques in patients undergoing carotid endarterectomy: a prospective pilot study.

Components of carotid atherosclerotic plaque can be analysed preoperatively by non-invasive advanced imaging modalities such as magnetic resonance imaging (MRI). The expression of matrix metalloproteinase-9 protein (MMP-9), which has a potential role in remodelling of atherosclerotic plaques, can be analysed immunohistochemically. The aim of the present prospective pilot study is to analyse histological characteristics and expression of MMP-9 in carotid plaques of patients undergoing carotid endarterectomy (CEA) and to investigate the correlation with preoperative clinical symptoms and MRI features.

Serotonin level and serotonin uptake in human platelets: a variable interrelation under marked physiological influences.

Background: Although it is known that platelet serotonin level (PSL) depends directly on platelet serotonin uptake (PSU) through the plasma membrane, reports on their interrelation are inconsistent. The aim of this study was to systematically explore the relationship between these two platelet serotonin parameters in large human population.

Methods: PSL and full-kinetics of PSU were determined on 318 blood donors (276 males, 42 females; 20-67 years).

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia.

Background: Genome-wide studies on autism spectrum disorders (ASDs) have mostly focused on large-scale population samples, but examination of rare variations in isolated populations may provide additional insights into the disease pathogenesis.

Methods: As a first step in the genetic analysis of ASD in Croatia, we characterized genetic variation in a sample of 103 subjects with ASD and 203 control individuals, who were genotyped using the Illumina HumanHap550 BeadChip. We analyzed the genetic diversity of the Croatian population and its relationship to other populations, the degree of relatedness via Runs of Homozygosity (ROHs), and the distribution of large (>500 Kb) copy number variations.

Association of serotonin transporter promoter (5-HTTLPR) and intron 2 (VNTR-2) polymorphisms with treatment response in temporal lobe epilepsy.

Purpose: Temporal lobe epilepsy (TLE) is the most common epilepsy and about 30% of patients have poorly controlled seizures. Neurobiology underlying responsiveness to medical treatment in TLE patients is unclear and there are currently no biological tests to predict course of the disease. Animal and human studies repeatedly suggested serotonergic dysfunction in subjects with TLE.

Platelet serotonin transporter (5HTt): physiological influences on kinetic characteristics in a large human population.

The present study had two goals: first, to give a detailed description of a reliable method for full kinetic analysis of serotonin transporter (5HTt) on the membrane of human platelets, and second, as a main issue, to report on physiological influences on kinetic characteristics of this transmembrane transport on a large population of healthy individuals. Full kinetic analyses of platelet serotonin uptake were performed on 334 blood donors of both sexes by the use of 14C-radioisotopic method, which was first optimized according to assumptions of enzyme kinetic analyses, with regard to platelet concentration, duration of uptake, concentration of substrate as well as important technical parameters (underpressure of filtration, blanks, incubating temperature, etc). Kinetic parameters of platelet serotonin uptake in the whole population were for V(max): 142 +/- 25.

5-HT2A receptor gene polymorphisms in Croatian subjects with autistic disorder.

Disturbances in the expression/function of the 5-HT2A receptor are implicated in autism. The association of the 5-HT2A receptor gene with autism was studied in the Croatian population. Distribution frequencies for alleles, genotypes and haplotypes of -1438 A/G and His452Tyr polymorphisms were compared in samples of 103 autistic and 214 control subjects.

5HT-1A receptors and anxiety-like behaviours: studies in rats with constitutionally upregulated/downregulated serotonin transporter.

Altered activity of brain serotonergic (5HT) system has been implicated in a wide range of behaviours and behavioural disorders, including anxiety. Functioning of 5HT-1A receptor has been suggested as a modulator of emotional balance in both, normal and pathological forms of anxiety. Here, we studied serotonergic modulation of anxiety-like behaviour using a genetic rat model with constitutional differences in 5HT homeostasis, named Wistar-Zagreb 5HT (WZ-5HT) rats.

Epilepsy and serotonin (5HT): variations of 5HT-related genes in temporal lobe epilepsy.

Several lines of evidence point to the role of serotonin (5HT) neurotransmission in the epileptogenesis. The present preliminary study investigated possible association of the temporal lobe epilepsy (TLE) with the polymorphisms in several 5HT-related genes, including serotonin transporter (5HTT), monoamine oxidase A (MAO-A) and serotonin receptors 5HT-1A, 5HT-1B and 5HT-2C. All participants (101 TLE patients and 170 healthy controls) were unrelated individuals of Croatian origin.

Hyperserotonemia in autism: the potential role of 5HT-related gene variants.

Increased platelet serotonin level (PSL) has been consistently found in a portion of autistic patients. Suggested mechanisms for hyperserotonemia in autism have been increased synthesis of serotonin (5HT) by tryptophan hydroxylase (TPH), increased uptake into platelets through 5HT transporter (5HTt), diminished release from platelets through 5HT2A receptor (5HT2Ar) and decreased metabolism by monoamine oxydase (MAOA). The allelic influence of genes, encoding the mentioned 5HT elements, on PSL was investigated in 63 autistic subjects.

Expression of 5HT-1A and 5HT-1B receptor genes in brains of Wistar-Zagreb 5HT rats.

By selective breeding, two sublines of rats with high or low activity of platelet serotonin (5HT) transporter (5HTt) have been developed (Wistar-Zagreb 5HT rats). Previous studies demonstrated significant differences between the sublines in the expression of platelet 5HTt at the level of both, mRNA and protein. Pharmacological studies showed marked alterations in brain 5HTt function, indicating differences in central serotonin homeostasis, although analysis of regional brain 5HTt gene expression did not show analogous differences.

Platelet monoamine oxidase kinetics, alcoholism subtypes and cigarette smoking.

In trying to dissociate the effect of alcohol and tobacco use on platelet monoamine oxidase-B (MAO-B) activity, we compared the enzyme kinetics in controls (n = 66) and alcohol-dependent patients (n = 81), subdivided according to the severity of both, alcohol and tobacco use. Platelet MAO-B kinetics was measured spectrophotofluorimetrically in chronic alcohol intoxication and after 3 weeks abstinence. In alcoholic patients, an increased Michaelis-Menten constant (16%, p < 0.

Effect of apomorphine on striatal synaptotagmin 7 mRNA levels in reserpinized rats.

Synaptotagmin 7 (Syt 7) is a Ca2+ sensor implicated in the regulation of membrane fusion in vesicular transport, but its precise role in neurons is still a matter of controversy. Dopaminergic drugs have been shown to modulate its expression in the striatum. Here we investigate whether dopamine receptor agonist-up-regulation of Syt 7 mRNA is specifically involved in the pathophysiological adaptations of hypersensitive striatum by analyzing other dopaminergic neurons containing brain regions.

Hyperserotonemia in adults with autistic disorder.

Hyperserotonemia is the most consistent serotonin-related finding in autism. The basis of this phenomenon, and its relationship to the central serotonergic dysfunction remains unclear. Platelet serotonin level (PSL) in 53 autistic adults and 45 healthy controls was measured.

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment.

Perinatal asphyxia is a concern for public health and may promote subtle and long-lasting neuropsychiatric disorders. In the present study, newborn Wistar rat pups underwent a repeated 20-min exposure to a 100% N2 atmosphere (or air) on postnatal days (pnd) 1, 3, 5, and 7. Half of the animals were housed during adolescence (pnd 21-35) in an enriched environment.

Rats with constitutionally upregulated/downregulated platelet 5HT transporter: differences in anxiety-related behavior.

Serotonin (5-hydroxytryptamine, 5HT) plays important roles in both embryonic development as a mediator of neurogenesis and in the mature brain as a neurotransmitter. Disturbances in serotonergic transmission have been indicated in several psychiatric disorders. In the search for the biological substrates of psychiatric diseases, studies using animal models represent complementary approaches to studies on human subjects.

Serotonin transporter kinetics in rats selected for extreme values of platelet serotonin level.

By selective breeding of Wistar rats for the extreme values of platelet serotonin (5HT) level (PSL), we have developed earlier two sublines of animals differing markedly in this parameter. Further studies, performed on the protein and mRNA levels, revealed platelet serotonin transporter (5HTt) as parameter underlying mentioned differences in PSL between sublines. In this work, we have performed full-kinetic analysis of platelet serotonin uptake (PSU) in animals from the genetically selected sublines.

Monoamine oxidases A and B gene polymorphisms in migraine patients.

Abnormal cortical activity and brainstem functioning are considered the possible etiopathogenetic factors of migraine. Monoamine oxidase A and B (MAO-A and -B) regulate the levels of monoamine neurotransmitters, so changes in their activity could participate in migraine pathogenesis. We have investigated the possible association of MAO-A and -B alleles and haplotypes with two common types of migraine, i.

Expression of brain and platelet serotonin transporters in sublines of rats with constitutionally altered serotonin homeostasis.

By selective breeding, two sublines of rats, termed Wistar-Zagreb 5HT rats, with constitutionally high or low values of platelet serotonin (5HT) level and activity of platelet serotonin transporter (5HTt) have been developed. Previous studies demonstrated significant differences between the sublines in the expression of platelet 5HTt at the level of both mRNA and protein. Neurochemical and behavioural studies demonstrated differences in functional activity of brain 5HTt indicating that, similarly to platelets, differences in mRNA level might be expected in brains of selected animals.