Inhibition of monoamine uptake in synaptosomes by tetrahydroharmane and tetrahydroisoquinoline compounds

Summary The effect of some tetrahydroharmane derivatives on the synaptosomal uptake of monoamines was studied. 1,2,3,4-Tetrahydroharmane (TH), which can be viewed as an analog of tryptamine, inhibited 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA) uptake, but TH was about 10 times less potent than tryptamine. 6-Hydroxy-1,2,3,4-tetrahydroharmane (6-HTH), a 5-HT analog, was slightly more potent an inhibitor of 5-HT uptake than TH, but as catecholamine uptake inhibitors these compounds were equipotent. Harmane-1,2,3,4-tetrahydro-3-carboxylic acid had no effect. Salsolinol and salsolidine, tetrahydroisoquinoline derivatives, were less potent than the harmane derivatives. It is to be concluded that also tetrahydroharmane derivatives have an affinity to the amine pump similarly to that of the tetrahydroisoquinolines, which are the corresponding analogs of catecholamines. These kinds of compounds are important because of the possibility that they may be formed in physiological conditions as condensation products of biogenic amines and aldehydes, e.g. acetaldehyde, which is an intermediate of ethanol metabolism.     

Cardiovascular and behavioural changes after i.c.v. infusions of histamine and agonists in conscious goat

Histamine (3 and 10 moles) raised the blood pressure in the conscious goat when given i.c.v. but lowered it when given intravenously. The results with 2-PEA support the view that central H₁-stimulation raises the blood pressure. However, the results with dimaprit do not exclude the participation of central H₂-receptors in the effect of histamine on the blood pressure.It appears that in the goat the stimulation of central H₁- and H₂-receptors mediates opposite actions on behaviour. H₁-agonist increased and H₂-agonist decreased the general activity of the animal.     

Strain differences in regional brain histamine levels between genetically epilepsy-prone and resistant rats.

In order to further elucidate the possible role of histamine in the seizure model, we determined the histamine levels in different brain regions of genetically epilepsy-prone Krushinski-Molodkina (KM) rats. Histamine levels in the striatum, hippocampus, amygdala, midbrain, thalamus and hypothalamus of KM rats were significantly lower than in the epilepsy-resistant Wistar rats. Previously, we have reported that the audiogenic seizures of KM rats were reduced by metoprine, which can markedly increase brain histamine. These findings are in agreement with the hypothesis that central histamine neuron system may be involved in the inhibitory mechanism of seizures.     

The concentrations of GABA, 5-HIAA and HVA in the cerebrospinal fluid of children with infantile spasms and the effects of ACTH treatment.

Children with infantile spasms (IS) are generally treated with ACTH although little is known of the biochemical basis of the symptoms and the mechanism of this therapy. We have measured the concentrations of gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of IS children, followed the effect of ACTH treatment on these parameters and correlated CSF GABA values with the cause of IS, cranial CT findings and antiepileptic treatment. While significant differences in GABA concentrations were found between the children with IS and those with febrile seizures or nonconvulsive symptoms, these could be accounted for by age, not the disease present. The CSF GABA level was highest in the IS children with normal CT, cryptogenic cause and no antiepileptic treatment, and lowest in those with abnormal CT, symptomatic cause and antiepileptic treatment. The basal level of CSF 5-HIAA in the IS children was higher than that in the nonconvulsive children, but HVA levels did not differ. ACTH therapy did not change the CSF levels of GABA, 5-HIAA and HVA significantly.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin enhances responsiveness to post-ingestive satiety signals

The present study was designed to characterize the hypophagia that is a salient feature of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced wasting syndrome. When TCDD-treated Long-Evans (L-E; dose 50 micrograms/kg) and Han-Wistar (H-W; 3000 micrograms/kg) rats were offered a simultaneous choice of three diets differing in their macronutrient composition, no selective aversion was seen to any of the varieties, although total energy intake decreased drastically and especially so in L-E rats. Further studies in H-W rats showed that TCDD treatment leads to a permanent retardation of weight gain accompanied by a decreased intake of chow and of a 10% sucrose solution, and to a reduced or unchanged consumption of water. In contrast, there was a progressive increase in saccharin drinking (when offered as the only choice) in TCDD-dosed rats with time. TCDD-treated animals also tended to consume a greater proportion of their daily feed intake during the daytime. These results imply that TCDD induces aversion to eating energy-providing food, irrespective of its type, and that TCDD exerts this at least in part by sensitizing the rats to post-ingestive satiety factors.     

Inhibition of experimental caries by plaque prevention

abstract – The purpose of this study was to test the hypothesis that a frequent intake of sucrose does not produce caries if the teeth are regularly treated with an antibacterial agent. Twenty-four students with clean teeth and normal gingivae were assigned to one of the following three groups: (1) eight individuals ceased all active oral hygiene measures and rinsed 9 times daily with 50% sucrose, (2) eight students refrained from all active oral hygiene procedures, rinsed 9 times daily with sucrose and twice daily with 10 ml 0.2% chlorhexidine gluconate, (3) the third group consisted of two subgroups each comprising 4 students. One subgroup ceased all oral hygiene procedures and rinsed twice daily with 0.2% chlorhexidine gluconate. The other was instructed to practice meticulous tooth brushing twice daily. The experiment lasted for 22 days. The group who rinsed with sucrose showed heavy plaque accumulation, those who rinsed with sucrose + chlorhexidine showed a drastic reduction in the formation of plaque. In the subgroup rinsing with chlorhexidine only and in that performing good oral hygiene, plaque was non-existent. The gingival state essentially paralleled the plaque formation. The sucrose group showed a definite increase in Caries Index. No significant changes occurred in the group rinsing with sucrose + chlorhexidine, with chlorhexidine only, or in the group performing good oral hygiene. It is concluded that prevention of plaque formation inhibits the development of gingivitis and dental caries, even with frequent rinses of sucrose.     

Integrated modeling assessments of the population exposure in Finland to primary PM2.5 from traffic and domestic wood combustion on the resolutions of 1 and 10 km

This study assesses population exposure caused by the emissions of primary fine particulate matter (PM_2.5) originated from road traffic and domestic wood combustion in Finland in 2000 and 2020. The evaluations were performed using source-receptor matrices (SRMs) based on the computations using a local and a regional scale atmospheric dispersion model, on two different grid resolutions: 1 and 10 km. Road traffic and domestic wood combustion are nationally the most important emission source categories of primary PM_2.5; they were projected to contribute to 42% of the Finnish total emissions in 2020. Although traffic exhaust emissions were projected to decrease considerably in the future, by 91% from 2000 to 2020, non-exhaust emissions were predicted to increase. Traffic emissions were found to cause on the average considerably higher population-weighted concentration (PWC) to primary PM_2.5, compared with domestic wood combustion emissions. Based on the computation with 1-km resolution SRMs, the exhaust and non-exhaust traffic emissions were projected to cause 5.5% and 62% of the PWC, respectively, of the total combined PWC caused by traffic and domestic combustion in Finland in 2020. Regarding the sub-categories of domestic wood combustion, supplementary wood heating was found to cause relatively high PWC, 22% in 2020. The modeling of traffic emissions and dispersion using the regional scale model on a resolution of 10 km resulted in PWC that is more than an order of magnitude smaller, compared with the corresponding computations using a local scale model on a resolution of 1 km. The general implication of this study is that the PWC values evaluated using integrated assessment models can be sensitive to the methodology, especially these can substantially increase with an increasing spatial resolution.     

Serum interleukin-2 receptor in infants and young children

Soluble interleukin-2 receptor (IL-2R) concentrations were measured in 110 serum samples from 102 children undergoing routine small bowel biopsy for a wide range of gastrointestinal symptoms. Young children in the control group who had no gastrointestinal disease and a normal intestinal mucosa were found to have high concentrations of IL-2R. There was a significant inverse relationship between IL-2R concentration and age in the control group. Children with a gastrointestinal diagnosis appeared to have increased IL-2R concentrations, although some of the diagnostic groups were too small in size for statistical analysis. Children with cow's milk sensitive enteropathy had IL-2R concentrations equivalent to those of age-matched controls. High concentrations of IL-2R in young healthy children implies that serum IL-2R is of no clinical use as an index of inflammation in this age group.