Remodelling and dysfunction of the sinus node in pulmonary arterial hypertension.

Patients with pulmonary arterial hypertension (PAH) have a high burden of arrhythmias, including arrhythmias arising from sinus node dysfunction, and the aim of this study was to investigate the effects of PAH on the sinus node. In the rat, PAH was induced by an injection of monocrotaline. Three weeks after injection, there was a decrease of the intrinsic heart rate (heart rate in the absence of autonomic tone) as well as the normal heart rate, evidence of sinus node dysfunction.

and its ingredient biopterin glucoside improved insulin sensitivity in non-alcoholic steatohepatitis model.

Non-alcoholic steatohepatitis is the chronic liver disease leading to cirrhosis and cancer and its prevalence is increasing. Some agents are under clinical trials for non-alcoholic steatohepatitis treatment. We previously reported effectively prevented non-alcoholic steatohepatitis progression in our model rats.

Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups.

Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mouse model.

Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities.

Effects of zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] and eugenol [2-methoxy-4-(2-propenyl)phenol] on the pathological progress in the 6-hydroxydopamine-induced Parkinson's disease mouse model.

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the nigrostriatal system and dopamine (DA) depletion in the striatum. The most popular therapeutic medicine for treating PD, 3-(3,4-Dihydroxyphenyl)-L-alanine (L-DOPA), has adverse effects, such as dyskinesia and disease acceleration. As superoxide (·O(2)(-)) and hydroxyl radical (·OH) have been implicated in the pathogenesis of PD, free radical scavenging and antioxidants have attracted attention as agents to prevent disease progression.

Effects of docosahexaenoic acid in an experimental rat model of nonalcoholic steatohepatitis.

Docosahexaenoic acid (DHA) regulates the lipid metabolism and inflammation that is closely associated with oxidative stress. The present study investigated the effects of DHA on the development of nonalcoholic steatohepatitis (NASH). To induce fatty liver, rats were fed choline-deficient high-fat diets (CDHF).

In vivo tissue uptake of intravenously injected water soluble all-trans beta-carotene used as a food colorant.

Water soluble beta-carotene (WS-BC) is a carotenoid form that has been developed as a food colorant. WS-BC is known to contain 10% of all-trans beta-carotene (AT-BC). The aim of the present study was to investigate in vivo tissue uptake of AT-BC after the administration of WS-BC into rats.

Docosahexaenoic acid ethyl ester enhances 6-hydroxydopamine-induced neuronal damage by induction of lipid peroxidation in mouse striatum.

Superoxide and hydroxyl radicals are implicated in the pathogenesis of Parkinson disease, and induction of lipid peroxidation is an important factor in progression of this disease. Docosahexaenoic acid (DHA) is a key component of the cell membrane, and its peroxidation is inducible due to the double-bond chemical structure. However, DHA has neuroprotective effects.

Eugenol [2-methoxy-4-(2-propenyl)phenol] prevents 6-hydroxydopamine-induced dopamine depression and lipid peroxidation inductivity in mouse striatum.

As superoxide (.O2-) and hydroxyl radical (.OH) have been implicated in the pathogenesis of Parkinson disease, free radical scavenging and antioxidants have attracted attention as way to prevent progression of this disease.

Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] prevents 6-hydroxydopamine-induced dopamine depression in mouse striatum and increases superoxide scavenging activity in serum.

As superoxide (*O(2)-) and hydroxyl radical (*OH) have been implicated in pathogenesis of Parkinson's disease, free radical scavenging, antioxidant, and neuroprotective agents have attracted attention as ways to prevent progression. We examined effects of zingerone, an alkaloid extracted from ginger root, on 6-hydroxydopamine (6-OHDA)-induced dopamine (DA) reduction in mouse striatum. Zingerone administration 1 h before and for 6 more days following one intracerebroventricular 6-OHDA injection prevented reductions of striatal DA and its metabolites, and increased serum *O(2)- scavenging activity.

Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice.

We investigated the modifications in endogenous antioxidant capacity and oxidative damage in the brain, liver, kidney and testis in mice exposed to bisphenol A (BPA), an environmental endocrine disrupter. Mice were exposed to BPA throughout embryonic/fetal life and during lactation by feeding their pregnant/lactating mothers BPA at 5 or 10 microg per milliliter of drinking water. At the age of four weeks, male mice were sacrificed.

Effects of bisphenol A on the metabolisms of active oxygen species in mouse tissues.

We investigated the modifications in endogenous antioxidant capacity, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, oxidative stress index, reduced glutathione (GSH), glutathione disulfide (GSSG), and thiobarbituric acid-reactive substance (TBARS) in the brain, liver, kidney, and testes of mice under bisphenol A (BPA), an endocrine disrupter, treated for 5 days. BPA was administrated intraperitoneally at doses of 25 and 50mg/kg/day. The TBARS levels were not affected by BPA administrations.

alpha-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy.

Intracortical injection of iron ions has been used to model post-traumatic epilepsy. The results obtained using these models suggest that oxidation of neural membranes by active oxygen free radicals may be involved in the etiology of post-traumatic epilepsy. This is a study of the effects of alpha-tocopheryl-L-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), known as a hydroxyl radical scavenger, on the peroxidation of neural membranes by FeCl(3) in vitro and on the occurrence of epileptic discharges in the FeCl(3) injected post-traumatic epilepsy model rats.

Activation of the bulbospinal serotonergic system during experimental tooth movement in the rat.

Experimental tooth movement is known to induce characteristic delayed and continuous nociception. Nociceptive somatic stimuli activate endogenous pain control systems such as descending monoaminergic pathways, which modulate the transmission of ascending sensory messages. To test the hypothesis that bulbospinal serotonergic pathways modulate subchronic nociception, we assayed the medulla at the level of the subnucleus caudalis and peri-aqueductal grey by high-performance liquid chromatography with electrochemical detection for the serotonin (5-hydroxytryptamine, 5-HT) and its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) 24 hrs after the onset of experimental tooth movement.

Effects of magnetic fields on the accumulation of thiobarbituric acid reactive substances induced by iron salt and H(2)O(2) in mouse brain homogenates or phosphotidylcholine.

In this study, we examined the effects of magnetic fields (MFs) on the generation of thiobarbituric acid reactive substances (TBARS) in the mouse brain homogenates or phosphotidylcholine (PC) solution, incubated with FeCl(3) and/or H(2)O(2). Active oxygen species were generated and lipid peroxidation was induced in mouse brain homogenates by incubation with iron ions, resulting in the accumulation of TBARS. Lipid peroxidation was induced in PC by incubation with iron ions and H(2)O(2).

Medullary monoamine levels during experimental tooth movement.

We investigated possible influence of nociception induced by experimental tooth movement on the medullary monoaminergic inhibitory systems. Forty-eight hours after the start of the experimental tooth movement, significant increases in dorsal serotonin (5-HT), dopamine (DA), norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), and dihydroxyphenylacetic acid (DOPAC) levels were detected with ipsilateral dominance. These results suggest that the nociception induced by experimental tooth movement might be under modulation of serotonergic, noradrenergic, and dopaminergic systems.

Alternate magnetic fields potentiate monoamine oxidase activity in the brain.

Catecholamines and serotonin, which act as neurotransmitters and regulate blood circulation, are degraded by monoamine oxidase (MAO) [EC 1.4.3.

Effects of an in vivo 60 Hz magnetic field on monoamine levels in mouse brain.

We studied the effects of electromagnetic fields (EMF) on mouse brain monoamine levels in models of (1) chronic exposure (7 days) of EMF (60 Hz, 10 Gauss) to mice in a vertical orientation, (2) prolonged chronic exposure (84 days) of EMF (60 Hz, 10 Gauss) to mice in a horizontal mode, (3) acute exposure (6 h) of EMF (60 Hz, 10 Gauss) to senescence accelerated mice (SAM-P8) at ages 1, 3, 6, 9 and 12 months in the horizontal mode, and (4) acute exposure (1 h) of EMF (60 Hz, 1, 3.3 and 10 Gauss) to restrained mice in the horizontal mode. No model except the restrained one changed their monoamine or metabolite levels by exposure to EMF.

Continuous monitoring of nitric oxide release induced by cholecystokinin from the choledochal sphincter in guinea pigs.

Background/aims: Many in vitro studies in the choledochoduodenal junction of the guinea pig have shown that cholecystokinin (CCK) contracts the sphincter of Oddi (SO). This study, using the choledochal sphincter of the guinea pig as the SO, evaluates the hypothesis that effects of CCK on the SO were mediated by nitric oxide (NO).

Methods: Spontaneous motility and effects of CCK on the choledochal sphincter were recorded using a constant-perfusion technique, and direct measurement of NO release using a specific NO sensor was performed at the same time.

EPC-K1, a hydroxyl radical scavenger, prevents 6-hydroxydopamine-induced dopamine depletion in the mouse striatum by up-regulation of catalase activity.

We examined the effect of pretreatment with EPC-K1, a potent hydroxyl radical scavenger, on 6-hydroxydopamine (6-OHDA)-induced reduction of dopamine (DA) and its metabolites in the mouse striatum. EPC-K1 was mixed with diet (0.2%, wt/wt) for 1 or 2 weeks, and then 6-OHDA (60 microg in 2 microl of saline solution) was injected intracereberoventricularly.

Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist.

Recent information suggests that free radicals are closely involved in the pathogenesis and/or progression of Parkinson's disease (PD). High-dose levodopa therapy has been suggested to increase oxidative stress, thereby accelerating the progression of PD. Based on this viewpoint, free radical scavenging, antioxidant and neuroprotective agents which may prevent the progression of PD have recently attracted considerable attention.

Is low density lipoprotein apheresis effective for coronary artery disease?

Low density lipoprotein (LDL) apheresis is one type of therapy currently being used for coronary artery disease; however, there has been no study to compare the effectiveness of this therapy with the effectiveness of other treatments, such as coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). In this study, we evaluated the clinical results of these three therapies to compare their individual effectiveness for the treatment of coronary artery disease. Forty-four patients with two vessel disease (plasma cholesterol levels > 250 mg/dl) were divided into three groups (L, LDL apheresis; C, CABG; I, PTCA).

Effects of kynurenine metabolites on the electrocorticographic activity in the rat.

We examined the effects of kynurenine metabolites administered into the right cerebroventricle (1 micromol) on the electrocorticogram (ECoG) of rats to establish the role of kynurenines on brain function. Kynurenine, anthranilic acid, quinaldic acid, xanthurenic acid or 8-hydroxyquinaldic acid showed no effect on ECoG throughout the recording period of 4 hours. 3-Hydroxykynurenine had a transient suppressive effect on the ECoG, while kynurenic acid caused a slight suppression of ECoG activity.

Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation.

Purpose: Intracortical injection of iron ion induces recurrent seizures and epileptic discharges in the electrocorticogram. This observation may be used as a model of posttraumatic epilepsy. The involvement of iron-mediated oxygen free radical species and neuronal lipid peroxidation in iron-induced seizure has been suggested.