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Biomedical subjects

M Yoshioka

Publications and source records attributed to M Yoshioka.

At least 127 records · Page 7Linked to original sources

Pharmacological characterisation of 5-HT receptors positively coupled to adenylyl cyclase in the rat hippocampus.

The pharmacological properties of 5-hydroxytryptamine (5-HT) receptors positively coupled to adenylyl cyclase in the rat hippocampus were investigated using selective agonists and antagonists. 5-HT (0.008-125 microM) stimulated cyclic AMP formation in homogenates of rat hippocampus in a concentration-dependent manner. The maximal increase in cyclic AMP formation occurred at 1 microM (141+/-6%) and the half-maximal effect (EC50) at 50+/-22 nM. Cyclic AMP accumulation induced by 1 microM 5-HT was partly inhibited by the selective 5-HT1A receptor antagonist WAY 100,635 (1 microM), the selective 5-HT4 receptor antagonist SB 203,186 (1 microM), and the 5-HT2A/c/ 5-HT7 receptor antagonist mesulergine (25 microM). WAY 100,635, SB 203,186 and mesulergine inhibited the effect of 5-HT (1 microM) by 47%, 33% and 49%, respectively. The combination of WAY 100,635 (1 microM) with SB 203,186 (1 microM) or mesulergine (25 microM) resulted in stronger inhibition than with each antagonist alone, and the combination of all three antagonists produced almost total blockade (95%) of 5-HT-induced cyclic AMP accumulation. 5-Carboxamidotryptamine (5-CT; 0.008-125 microM), a 5-HT1/5-HT7 receptor agonist, and SDZ 216-454 (0.008-125 microM), a selective 5-HT4 receptor agonist, concentration-dependently stimulated cyclic AMP formation, but the maximal effect of each agonist was smaller than that of 5-HT alone. SDZ 216-454 (5 microM) and 5-CT (5 microM) in combination stimulated cyclic AMP formation in an additive manner. 8-OH-PIPAT and 8-OH-DPAT, two selective 5-HT1A agonists, produced a small but significant increase in cyclic AMP formation at concentrations above 0.04 microM and 10 microM, respectively. These findings suggest that at least three 5-HT receptor subtypes, i.e. 5-HT1A, 5-HT7 and 5-HT4 receptors, are involved in mediating 5-HT-induced cyclic AMP formation in rat hippocampus.

Adenylyl Cyclases↗

Regression of the hyaloid vessels and pupillary membrane of the mouse.

Regression of the pupillary membrane (PM) and hyaloid vessels - hyaloid arteries (HAs), tunica vasculosa lentis (TVL), and vasa hyaloidea propria (VHP) - in mice aged from 0 to 16 days was observed using stereomicroscopy and transmission electron microscopy. Whole-mount stereomicroscopy revealed that the pattern of normal developed vessels was basically the same as that reported in rats and rabbits and that the VHP and PM disappeared between 12 and 16 days and 10 and 12 days, respectively, while certain examples of the TVL and HA remained even at 16 days. In the TVL, VHP and PM, regression occurred segmentally and resulted in a decreased number of interconnections. The ultrastructure of the vessels in the VHP, TVL and PM was consistent with a typical capillary with pericyte covering and no fenestrations. HAs had tunica media and adventitia in the older stages. Some endothelial cells in the TVL and PM attaching to the lens capsule were thin at the side of the lens. Many macrophages were observed in the vitreous and around vessels in the whole-mount specimens at all stages. Some macrophages remained linearly arranged even after vessels became vestigial and disappeared. In transmission electron microscopy, most of these macrophages were seen to possess vacuoles and/or processes, and some of them had phagosomes. Electron microscopic findings from regressing ocular vessels were consistent with the apoptosis of both endothelia and pericytes. Obstruction of the vessels was noted at older stages. These results add further anatomical information to previous studies and suggest that the VHP and TVL as well as PM regress via apoptosis. The precise mechanisms of regression of hyaloid vessels and the role of macrophages remain for further studies.

Animals↗

Identification of connexins in human oral mucosa and therapeutic effect of irsogladine maleate on aphthous stomatitis.

We identified connexins 26 and 32 in human oral mucosa. The presence of the connexins indicates the presence of gap junctions in this tissue. However, immunofluorescence study found no significant differences in the expression of the connexins between patients with aphthons stomatitis and controls. Irsogladine maleate, which reinforces gap junctional intercellular communication in vitro, was effective for the treatment of transient and relapsing aphthous stomatitis, as well as symptomatic and drug-induced aphthous stomatitis. It was also useful for prevention of episodes of relapsing aphthous stomatitis, with daily administration preverting recurrence of stomatitis for more than 4 years one patient. These findings suggest that irsogladine maleate accelerates the wound healing process in oral mucosa by reinforcing gap junctional intercellular communication among oral mucosal cells; and that it is useful for the treatment and prevention of aphthous stomatitis.

Adult↗

Osteoporosis influences the late period of fracture healing in a rat model prepared by ovariectomy and low calcium diet.

To elucidate the influence of osteoporosis on the fracture healing, we produced a rat osteoporosis model by ovariectomy and by maintaining a low calcium diet; and monitored the healing process radiographically, histologically, and biomechanically for 12 weeks. Radiologic, histologic and biomechanical findings of the fracture areas 6 weeks after making the fractures were almost identical in both the osteoporosis group and the control group. However, 12 weeks after making the fractures, newly generated bones in the osteoporosis group showed histological osteoporotic changes and their bone mineral density on the fracture site decreased. These findings show that estrogen-deficient and low calcium conditions greatly affect the bone in the later period of the healing process, but do not affect remarkably the early healing period. This is clinically important when we consider fracture treatments for patients with osteoporosis due to menopause.

Animals↗

Effect of filler content and size to properties of composite resins on microwave curing.

The effect of filler content and size to property of composite resin using high purity spherical silica particles on microwave curing was examined by mechanical means and electron microscope observation to develop microwave-curing composite resin inlay. Increasing filler content in three kinds of filler particles (0.45, 0.96 and 1.46 microm) resulted in increasing compressive strength, diametral tensile strength and knoop hardness and indicated the highest values at the operative mixing limit. The effect of particle size was that the mechanical property of the 0.96 microm filled resin was highest, followed by 1.46 microm and 0.45 microm on the same filler content. The 0.96 microm filled resin had about the same knoop hardness on both surfaces of the cured sample, which means that uniform polymerization occurred in the cured sample. With electron microscope observation, the bubbles of about 1.0 microm and the cracks between the fillers and the matrix were observed in each cured resin. This is caused by the excessive absorption of microwave energy in fillers and surface treatment materials of fillers. Therefore, improvement of the composition of filler and surface treatment material of filler are needed, which makes it harder to absorb the microwave energy.

Journal Article↗

Influence of polymerization initiator for base monomer on microwave curing of composite resin inlays.

Microwave polymerization was used to make composite resin inlays and the effect examined of the concentration of polymerization initiator for the base monomer. The monomers used were 2,2-bis [4-(3-methacriloxy-2-hydroxypropoxy) phenyl] propane (Bis-GMA) and triethyleneglycol dimethacrylate (TEGDMA). Bis-GMA and TEGDMA were mixed in a ratio of 6:4 by weight and were separated into five groups. To each group was added benzoyl peroxide (BPO) in the ratios of 0.1, 0.3, 0.5, 0.7 and 0.9 wt% as the polymerization initiator. These were used as the base monomers. The results showed that the degree of conversion of the cured sample increased with increasing concentration of BPO from 0.1 to 0.5 wt%, however there was no significant difference at 0.5, 0.7 and 0.9 wt% (P> 0.01). Compression strength, diametral tensile strength and the Knoop hardness showed a similar tendency as the degree of conversion. No significant difference was recorded in the Knoop hardness between the top and the bottom surfaces (P> 0.01), which suggested a uniform polymerization in the cured sample. Thus, microwave polymerization would be an efficacious method for making resin inlays with the addition of BPO to the base monomer (Bis-GMA:TEGDMA, 6:4). The maximum conversion was found at a concentration of 0.5 wt%.

Benzoyl Peroxide↗

Changes in renal blood flow in response to sympathomimetics in the rat transplanted and denervated kidney.

BACKGROUND: Renal denervation and re-innervation may affect vascular responses to sympathomimetics, which may play a role in the maintainance of renal blood flow (RBF) following renal transplantation. The purpose of the present study was to elucidate pharmacological alteration of the renal sympathetic response following kidney transplantation. Using the rat kidney transplantation model, we focused on responses to various sympathomimetics in order to investigate the effects of sympathetic denervation and functional remodulation mechanisms in the transplanted kidney. METHODS: Male isogenic rats underwent unilateral kidney denervation or kidney transplantation accompanied by unilateral native nephrectomy. Renal blood flow was evaluated using a laser Doppler flow meter following bolus injection of 50 microg/kg dopamine and continuous infusion of 60 microg/min phenylephrine (PE) at 0, 30, 60, 90 and 240 days after transplantation as well as at 30 days after denervation. RESULTS: Bolus injection of dopamine (50 microg/kg) induced an initial reduction in RBF (that of alpha-adrenoceptors) followed by a long-lasting increase in RBF (that of beta-adrenoceptors) in the native kidney. In grafted or denervated kidneys, the dopamine-induced decrease in RBF mediated by alpha-adrenoceptors was markedly enhanced while the increase in RBF mediated by an action of dopamine on beta-adrenoceptors was blunted. The effects of the post-transplant period on vascular responses to dopamine were significant, but not completely synchronized with the native kidney, even at 240 days. Continuous infusion of PE (60 microg/min) produced a gradual increase in RBF in the native kidney, whereas a sudden reduction (i.e. breakthrough in autoregulation) was observed in the denervated and transplanted kidney. CONCLUSIONS: The responses to sympathomimetics in the grafted kidney were shifted towards flow reduction (i.e. enhanced vasoconstriction via stimulation of alpha-adrenoceptors and blunted vasodilatation via stimulation of beta-adrenoceptors. This functional impairment was recovered in a time-dependent manner. In addition, the hemodynamic autoregulation system in the kidney deteriorated following transplantation or denervation.

Animals↗

Effects of bifemelane on incomplete cerebral ischaemia-induced reduction of long-term potentiation in rat hippocampal neurones in vivo.

In the present study, we investigated the effects of bifemelane on the reduction of hippocampal long-term potentiation after transient ischaemia. Bilateral common carotid arteries were clamped for 10 min. in halothane-anaesthetized rats. Thirty min. before occlusion, bifemelane (25 mg/kg, intraperitoneally) or saline was administered to the rats. Four days after occlusion, we measured long-term potentiation in Schaffer collateral-CA1 synapses and perforant path-dentate gyrus synapses in vivo. Long-term potentiation was significantly reduced in both the Schaffer collateral-CA1 and perforant path-dentate gyrus synapses in the saline-injected group. However bifemelane decreased the ischaemia-induced reduction of long-term potentiation in perforant path-dentate gyrus synapses, but not in Schaffer collateral-CA1 synapses. The findings suggest that bifemelane deserves further attention with regard to possible protective role in ischaemia.

Animals↗

Broader clinical spectrum of Fukuyama-type congenital muscular dystrophy manifested by haplotype analysis.

Fukuyama-type congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease are clinically similar autosomal-recessive diseases, characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. The classification of these disorders remains controversial. We analyzed five patients with congenital muscular dystrophy from four families who had severe eye and brain anomalies, such as retinal dysplasia and hydrocephalus, using polymorphic microsatellite markers flanking the Fukuyama-type congenital muscular dystrophy locus on chromosome 9q31. All patients were heterozygous for the Fukuyama muscular dystrophy founder haplotype with 3-kb insertion. In three cases, the other chromosome without the 3-kb insertion exhibited the same haplotype with a nonsense mutation on exon 3 of the Fukuyama gene. Thus, these three patients were compound heterozygotes for the condition. Severe eye anomalies such as retinal dysplasia or detachment and hydrocephalus could be included in the clinical spectrum of Fukuyama muscular dystrophy. The clinical spectrum of this disease is much broader than previously presumed.

Abnormalities, Multiple↗

Studies on interactions between traditional herbal and Western medicines. I. Effects of Sho-seiryu-to on the pharmacokinetics of carbamazepine in rats.

The effects of oral co- and pre-administration of Sho-seiryu-to extract powder (TJ-19, 1 g/kg), a widely used Kampo (traditional Chinese herbal) medicine, on the pharmacokinetics of an anti-epileptic drug, carbamazepine (CBZ), and its active metabolite (carbamazepine-10,11-epoxide, CBZ-E) after oral administration of CBZ (50 mg/kg) were examined in male rats. The simultaneous administration of TJ-19 significantly lengthened the time to reach the peak plasma concentration (Tmax), but did not influence the peak plasma concentration, area under the plasma concentration-time curve or terminal elimination half-life (t1/2). Each parameter for CBZ or CBZ-E with a single pretreatment with TJ-19 was not significantly different from that with the vehicle. Tmax and the elimination rate constant for CBZ were significantly increased by 1-week repeated pretreatment with TJ-19, by 83% (p<0.01) and 88% (p<0.001), respectively. t1/2 and the mean residence time from zero to infinity (MRT0-infinity) in the TJ-19 pretreatment group were significantly shortened, by 52 and 34% (p<0.005), respectively. No significant difference in the bound fraction of each drug at two concentrations (1 and 10 microg/ml) was observed between the control and TJ-19 pretreatment groups. These results indicate that simultaneous oral administration of TJ-19 delays the oral absorption of CBZ, while 1-week repeated pretreatment with TJ-19 accelerates the metabolism of CBZ in rats, without affecting the protein binding of CBZ.

Analysis of Variance↗

[Effects of isatin, an endogenous MAO inhibitor, on dopamine (DA) and acetylcholine (ACh) concentrations in rats].

Isatin (indole-2,3-dione), an endogenous inhibitor of monoamine oxidase (MAO), has several physiological properties for stress and anxiety. We previously identified isatin in the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using gas-chromatography mass spectrometry. This study elucidated the effects of isatin on the ACh and DA levels of brain tissues in rats. Furthermore, we evaluated the effect of isatin on DA levels in a rat model of Parkinson's disease induced by Japanese encephalitis virus. Striatal ACh and DA levels significantly increased at 2 hours after isatin (50-200 mg/kg, i.p.) administration. Perfused through a microdialysis probe, isatin (10(-6)-10(-4) M) also produced a significant and concentration-dependent increase in the ACh and DA concentrations in the perfusate from the rat striatum. Furthermore, urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. Isatin (100 mg/kg, i.p.) significantly increased striatal DA levels in a rat model of Parkinson's disease. These results suggest that urinary isatin may become a diagnostic marker for the clinical severity of Parkinson's disease and that endogenous isatin, a new biological modulator, may play a role in the regulation of the brain levels of ACh by increasing the level of DA under stress.

Acetylcholine↗

[Assessment of oxygen transport in individual splanchnic organs using critical oxygen extraction].

Vulnerability in individual organs under ischemic stress can be assessed by critical oxygen extraction (critical O2ER). We measured critical O2ER in the whole-body, total splanchnic organs, liver and gut using a biphasic regression model of the oxygen delivery-consumption relationship in 7 dogs subjected to hemorrhagic stress under 1% isoflurane anesthesia. The difference in critical O2ER between the whole-body and total splanchnic organs was not significant, while hepatic critical O2ER was significantly larger than that of the gut (P < 0.05), 89.7 +/- 2.4% (mean +/- SD) and 66.1 +/- 5.1%, respectively. This finding indicated that the liver functions well under ischemic conditions due to its excellent ability to extract oxygen. The anatomical character of the sinusoid and the microcirculatory improving effect of isoflurane may affect the ability of oxygen extraction of the liver. The critical threshold of hepatic venous oxygen saturation as a marker of hepatic oxygen imbalance was considered to be below 10%.

Anesthesia, Inhalation↗

Pharmacokinetic and pharmacodynamic interactions among haloperidol, carteolol hydrochloride and biperiden hydrochloride.

A beta-adrenoceptor blocker and an anticholinergic agent are often prescribed concomitantly for the treatment of neuroleptic-induced akathisia. The aim of this study was to investigate possible pharmacokinetic interactions of neuroleptic haloperidol with the beta-blocker carteolol and the anticholinergic biperiden. In a 5-step, open-labeled, oral single-dose study, eight healthy male volunteers received 2 mg haloperidol, 10 mg carteolol hydrochloride, and 2 mg biperiden hydrochloride: first each drug alone, then a combination of haloperidol and carteolol, and then all three drugs concurrently. Serum concentrations of haloperidol, carteolol, and biperiden were determined up to 24 hr postdosing, and a safety evaluation was conducted throughout the study. Carteolol increased the area under the haloperidol serum concentration-time curve (AUC0-t) 1.4-fold (P = 0.0014) and decreased the serum clearance of haloperidol up to 67% (P = 0.0127). Biperiden reduced the serum haloperidol concentrations increased by the administration of carteolol. No significant changes of the serum pharmacokinetics of carteolol and biperiden were found as a result of any drug combinations. Adverse events of the central nervous system such as sleepiness and changes in pupil size were observed, but all were mild with clinical insignificance.

Adrenergic beta-Antagonists↗

Significance of three-field lymphadenectomy for carcinoma of the thoracic esophagus based on depth of tumor infiltration, lymph nodal involvement and survival rate.

BACKGROUND: Significance of three-field lymhpadenectomy for carcinoma of the thoracic esophagus was examined retrospectively based on depth of tumor infiltration, lymph nodal involvements and long-term survival. METHODS: One hundred and fifty-two consecutive patients who underwent curative esophagectomy for thoracic carcinoma invading to submucosa (pT1) or deeper layers of the esophageal wall from 1983 to 1996 were examined. Sixty-six patients underwent three-field lymphadenectomy (3F) and 86 underwent two-field lymphadenectomy (2F). Survival curves were compared between 3F and 2F after stratifications according to depth of tumor infiltration, the number of positive nodes (0, 1 to 4, 5 or more), and positive intrathoracic recurrent nerve-chain nodes. RESULTS: Overall 5-year survival rate for 3F was 43.8%, while it was 30.2% for 2F (p = 0.07). In 41 patients with pT1 cancers, the 5-year survival rate for 3F was 55.7%, while it was 41.4% for 2F (p = NS). In patients with cancers invading to muscularis propria (pT2), the 5-year survival rate for 3F was 49.4%, while it was 30.7% for 2F (p = 0.06). In patients with tumors invading to adventitia, there was no significant difference. In patients with one to four positive nodes, the 5-year survival rates for 3F was 50.1%, while it was 24.1% for 2F (p = 0.01). There was no significant difference in the subgroups with no positive nodes and five or more. In subgroups with positive recurrent nerve-chain nodes, the 5-year survival rate for 3F was 27.9%, while it was 0% for 2F (p = 0.01). CONCLUSIONS: Significance of three-field lymphadenectomy was found in patients with one to four positive nodes or positive intrathoracic recurrent nerve-chain nodes.

Adenocarcinoma↗

Efficacy of two dentifrices on removal of natural extrinsic stain.

PURPOSE: To evaluate the 6-week effect on natural extrinsic dental stain from the use of a dentifrice containing 10% aluminum oxide, 1500 ppm sodium monofluorophosphate in a precipitated calcium carbonate (PCC) base or a second dentifrice containing 0.5% calcium peroxide (CP), 1500 ppm sodium monofluorophosphate in a PCC base compared to a fluoride placebo dentifrice without stain removal ingredients. MATERIALS AND METHODS: A total of 94 subjects were entered in the study, and stratified into three balanced groups according to their baseline mean Lobene Stain Index scores. The three groups were randomly assigned to use one of the two test dentifrices or the placebo dentifrice. The three groups were well balanced with regard to their mean baseline stain index scores, gender and tobacco habits. Subjects were instructed to brush their teeth twice daily (morning and evening) for 1 minute with their assigned dentifrice and a commercially available soft bristled toothbrush. Extrinsic dental stain examinations, which included mean stain area and mean stain intensity, were conducted at baseline and 6 weeks. Examinations were conducted by the same dental examiner (F.A.) on the subjects at each examination. RESULTS: After 6 weeks' use of their assigned products, those subjects in the aluminum oxide/PCC dentifrice group and those subjects in the CP/PCC dentifrice group demonstrated statistically significant improvements, as compared to the fluoride placebo dentifrice group without stain removal ingredients.

Adolescent↗

Effects of red pepper on appetite and energy intake.

Two studies were conducted to investigate the effects of red pepper (capsaicin) on feeding behaviour and energy intake. In the first study, the effects of dietary red pepper added to high-fat (HF) and high-carbohydrate (HC) meals on subsequent energy and macronutrient intakes were examined in thirteen Japanese female subjects. After the ingestion of a standardized dinner on the previous evening, the subjects ate an experimental breakfast (1883 kJ) of one of the following four types: (1) HF; (2) HF and red pepper (10 g); (3) HC; (4) HC and red pepper. Ad libitum energy and macronutrient intakes were measured at lunch-time. The HC breakfast significantly reduced the desire to eat and hunger after breakfast. The addition of red pepper to the HC breakfast also significantly decreased the desire to eat and hunger before lunch. Differences in diet composition at breakfast time did not affect energy and macronutrient intakes at lunch-time. However, the addition of red pepper to the breakfast significantly decreased protein and fat intakes at lunch-time. In Study 2, the effects of a red-pepper appetizer on subsequent energy and macronutrient intakes were examined in ten Caucasian male subjects. After ingesting a standardized breakfast, the subjects took an experimental appetizer (644 kJ) at lunch-time of one of the following two types: (1) mixed diet and appetizer; (2) mixed diet and red-pepper (6 g) appetizer. The addition of red pepper to the appetizer significantly reduced the cumulative ad libitum energy and carbohydrate intakes during the rest of the lunch and in the snack served several hours later. Moreover, the power spectral analysis of heart rate revealed that this effect of red pepper was associated with an increase in the ratio sympathetic: parasympathetic nervous system activity. These results indicate that the ingestion of red pepper decreases appetite and subsequent protein and fat intakes in Japanese females and energy intake in Caucasian males. Moreover, this effect might be related to an increase in sympathetic nervous system activity in Caucasian males.

Adult↗

The release of tumor necrosis factor-alpha, interleukin-1, interleukin-6 and prostaglandin E2 in bovine Kupffer cells stimulated with bacterial lipopolysaccharide.

Kupffer cells, in response to gut-derived bacteria, viruses and endogenous endotoxins, are thought to be a major source of proinflammatory cytokines and other mediators. In the present study, we investigated the mode of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) production by bovine Kupffer cells in response to LPS in vitro. By semi-quantitative reverse transcription-polymerase chain reaction, both TNF-alpha and IL-1beta mRNAs were expressed between 3 and 12 h after stimulation with 1 microg/ml of LPS. The IL-1alpha transcript also increased at 3 h, and then disappeared at 6 h. Although IL-6 mRNA was slightly expressed without stimulation, it increased and reached a peak after 6 h, and then decreased to normal levels by 24 h. The secretion of TNF-alpha and IL-1 was detected after 3 h and increased until 12 and 24 h, respectively, as detected by bioassay. IL-6 was secreted at a low level without stimulation, peaked 6 h after stimulation and remained elevated until 24 h. The secretion of prostaglandin E2 continued to increase for 24 h. These results suggest that several inflammatory cytokines released from bovine Kupffer cells are regulated in different modes.

Animals↗