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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 271 records · Page 15Linked to original sources

Chronic progressive spinocerebellar syndrome associated with antibodies to human T-lymphotropic virus type I: clinico-virological and magnetic resonance imaging studies.

The relationship between HTLV-I infection and the development of spinocerebellar degeneration (SCD) in adulthood was studied. The frequency of anti-HTLV-I antibodies among patients with SCD (8 of 43, 19%) was found to be higher than the seroprevalence rate in the northern part of Kyushu island (6%). All HTLV-I carriers with SCD showed chronic progressive cerebellar ataxia as a predominant feature and cerebellar atrophy was evident in 6 of 8 patients on magnetic resonance imaging (MRI) of the brain. However, SCD patients with anti-HTLV-I antibodies showed a significantly higher frequency of cerebral white matter lesions on brain MRI (6 of 8) and pyramidal tract signs in lower extremities (6 of 8) than did those without the antibodies (35%, P < 0.05 and 26%, P < 0.01, respectively). Moreover, the HTLV-I carriers with SCD exceeded 14 HTLV-I carriers having neither SCD nor HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (21%, P < 0.05), and 59 HTLV-I seronegative patients without brain disorders (19%, P < 0.001) in the frequency of white matter lesions. On the other hand, the HTLV-I carriers with SCD were distinct to the HAM/TSP patients in the predominance of cerebellar involvement. Therefore, the peculiar features of cerebellar, pyramidal and white matter involvement in the HTLV-I-seropositive SCD patients as well as the increased frequency of HTLV-I infection among SCD patients suggest that this syndrome may be a distinct subtype of HTLV-I-associated neurologic diseases.

Aged↗

Cerebral glucose metabolism and striatal 18F-dopa uptake by PET in cases of chorea with or without dementia.

Cerebral glucose metabolism was studied by positron emission tomography with [18F]fluorodeoxyglucose in 12 patients with chorea due to different underlying diseases. The striatal 18F-dopa uptake was also studied with 6-L-[18F]fluorodopa in 6 of them. Five of them were diagnosed as Huntington's disease two were as 'sporadic progressive chorea and dementia' with characteristic symptoms and signs of Huntington's disease but no family histories, two were as choreoacanthocytosis, and two had hemichorea caused by suspected vascular lesions in the contralateral striatum revealed by MRI. Caudate and putaminal glucose metabolism decreased in chorea compared to the controls. Hemichorea showed decreased glucose metabolism only in the contralateral striatum. Moreover the glucose metabolism decreased in demented each 7 patients in the frontal, temporal and parietal cortices as well as in the striatum. The caudate and putaminal 18F-dopa uptake in patients with chorea showed no difference with that in the controls. The pathogenetic mechanism of chorea may involve decreased glucose metabolism and normal presynaptic dopaminergic activity in the striatum, and that of the demented state in chorea may also involve an additional decrease of the glucose metabolism in the frontal, temporal and parietal cortices.

Adult↗

Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion.

Using intracellular recording techniques, we examined the effects of tachykinin receptor agonists and antagonists on electrophysiologically identified tonic neurons of the isolated guinea pig coeliac ganglion. In most of the tonic neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a depolarization. The effects of SP and NKA were blocked by the NK1-selective antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877 (10 microM), whereas the effect of senktide was not affected by these antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked depolarizations in tonic neurons. By contrast, the NK2-selective agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke any significant depolarizing response. Repetitive electrical stimulation of the mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the majority of tonic neurons, which were depressed by GR71251 (5 microM). These results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced response is due to the activation of NK1 receptors. This study also suggests the involvement of NK1 receptors in the slow EPSPs in tonic neurons.

Animals↗

Physicochemical stability of phenobarbital polymorphs at various levels of humidity and temperature.

The physicochemical stability of six phenobarbital modifications [forms A, B, C (monohydrate), D (dioxane solvate), E (hemihydrate), and F] at various levels of humidity and temperature were measured using X-ray diffractometry and differential scanning calorimetry. Form D was identified as a new crystalline form (dioxane solvate). Polymorphic transformations of the modifications were investigated by the Kissinger method under nonisothermal conditions. Change of polymorphic content of phenobarbital modifications under various humidity levels at 45 degrees C was evaluated by X-ray powder diffraction. The polymorphic stability under isothermal conditions was estimated kinetically, based upon the Jander equation. Forms A, B, and F were stable at 0 and 75% RH and 45 degrees C for 3 months. On the contrary, forms C, D, and E transformed during storage. The transformation rates of form D were larger than that of forms C and E.

Calorimetry, Differential Scanning↗

Evaluation of the ratio method compared with graphical analyses for estimating nigrostriatal function in human 18F-dopa PET studies with or without carbidopa.

The striatal to cerebellar (S/C) activity ratio for estimating nigrostriatal function was compared with the Patlak analyses in 18F-dopa (FD) positron emission tomography (PET) with pretreatment with 100 mg carbidopa (CD). Two different time-activity curves of plasma FD or cerebellar 18F were used for the Patlak analyses. The S/C ratio increased linearly with time for 120 min and the ratio at 120 min correlated closely with the uptake constants by the two Patlak analyses (r = 0.94, 0.96) in six normal volunteers and six parkinsonism patients. The S/C ratio and the uptake constant by the cerebellar Patlak analysis without CD also showed a fairly good correlation (n = 30, r = 0.85). Then, the S/C ratios with and without CD were compared. Since CD increased both the striatal and the cerebellar radioactivities proportionally within each subject, CD did not change the S/C ratios. The S/C ratios both with and without CD were simple and comparable to the uptake constants in the FD PET studies.

Adult↗

Depression of primary afferent-evoked responses by GR71251 in the isolated spinal cord of the neonatal rat.

1. The pharmacological profile of GR71251, a new tachykinin receptor antagonist, and its effect on the responses evoked by stimulation of primary afferent fibres were studied in isolated spinal cord preparations of neonatal rats. Potential changes were recorded extracellularly from a lumbar ventral root (L3-L5). 2. Bath-application of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) at 0.01-3 microM to the spinal cord induced depolarization of the ventral root in normal artificial cerebrospinal fluid (CSF). The NK1 agonist, acetyl-Arg6-septide, and the NK3 agonist, senktide, at 0.01-3 microM, also had potent depolarizing actions whereas two NK2 agonists, beta-Ala8NKA4-10 and Nle10NKA4-10, showed little depolarizing effects at 1 microM. 3. GR71251 (0.3-3 microM) caused a rightward shift of the concentration-response curves for SP, acetyl-Arg6-septide and NKA with pA2 values of 6.14, 6.75 or 6.70, respectively. The effects of GR71251 were readily reversible within 15-30 min after its removal. By contrast, GR71251 (1-5 microM) had little effect on the depolarizing responses to NKB and senktide. 4. GR71251 (1-3 microM) did not depress the depolarizing responses to bombesin, neuromedin B and gastrin-releasing peptide in normal artificial CSF. 5. Application of capsaicin to the spinal cord induced a depolarizing response, which was partially depressed by GR71251 (3-10 microM). 6. In the isolated spinal cord preparation, intense electrical stimulation of a dorsal root evoked a slow depolarizing response of the contralateral ventral root of the same segment. A similar slow ventral root depolarization was evoked by electrical stimulation of the ipsilateral saphenous nerve in an isolated spinal cord-saphenous nerve preparation. GR71251 (0.3-10 microM) dose-dependently depressed these slow ventral root potentials.7. In the spinal cord-peripheral nerve preparation, conditioning stimulation of the saphenous nerve evoked an inhibition of the muscle nerve-evoked monosynaptic reflex lasting about 20 s. The late part of the inhibition was markedly depressed by GR71251 (1-3 microM).8. The present results indicate that GR71251 is a potent and specific antagonist for tachykinin receptors in the spinal cord. The present study further provides evidence for the involvement of SP and NKA in the slow ventral root depolarization and the prolonged inhibition of monosynaptic reflex that are evoked by primary afferent stimulation.

Analgesics↗

Effect of humidity on solid-state isomerization of various kinds of lactose during grinding.

The effect of humidity on isomerization during grinding of alpha-monohydrate, alpha-anhydrate and beta-anhydrate of lactose was investigated. Samples were ground in an agate centrifugal ball mill at 270 rev min-1 at room temperature (21 degrees C) and at 5 and 60% relative humidity. Crystallinity of the ground lactose was measured by Hermans' method from the powder X-ray diffraction profiles. The alpha- and beta-lactose content of the ground lactose was measured by using angular rotation spectrophotometry. The crystalline lactose samples were transformed into noncrystalline solids by mechanical stress during grinding. After grinding, the adsorbed water content of all ground lactose samples increased, and the isomerized amount increased with increase of the water content during grinding at 5 and 60% relative humidity. The results suggest that the isomerization rate of alpha-monohydrate during grinding may depend on the crystallinity, but those of alpha- and beta-anhydrate depend on the content of adsorbed water.

Crystallization↗

Effect of environmental humidity on the transformation pathway of nitrofurantoin modifications during grinding and the physicochemical properties of ground products.

The effect of humidity on the physicochemical properties of nitrofurantoin anhydrate and monohydrate during grinding in a humidity-controlled system was investigated using X-ray diffraction analysis, IR spectroscopy, thermal analysis and scanning electron microscopy. Anhydrate and monohydrate were transformed into a noncrystalline solid and a stable monohydrate, respectively, during grinding in a closed system. During grinding in an open system, in which the humidity level of the air was controlled (5, 50 and 75% r.h.), the anhydrate absorbed moisture from the supplied air and water content was increased at 75% r.h.; thereafter the compound was transformed into monohydrate II. The anhydrate did not absorb at 5 or 50% r.h. and was transformed into a noncrystalline solid. Monohydrate I desorbed crystal water during grinding at 5% r.h. and was transformed into a noncrystalline solid. However, monohydrate I was transformed into monohydrate II at 50 and 75% r.h. without desorption of crystal water. These results suggest that the solid-state transformation of nitrofurantoin during grinding depends upon the environmental humidity.

Anhydrides↗

Radial arterial spasm in uremic patients undergoing construction of arteriovenous hemodialysis fistulas: diagnosis and prophylaxis with intravenous nicardipine.

Radial arterial spasm in uremic patients undergoing construction of internal arteriovenous (AV) dialysis fistulas was investigated transcutaneously using ultrasonic Doppler flowmetry. In 5 of 15 patients, radial arterial blood flow was significantly decreased 5 min after anastomosing the radial cephalic vein with the radial artery (14.3 +/- 4.5%, mean +/- SE, of the initial value; p < 0.001 vs. the initial blood flow), indicating vasospasm. Vasospasm disappeared 20 min after anastomosing. In 10 patients who were continuously given nicardipine intravenously (1 microgram/kg/min) during surgery, vasospasm did not occur. Arterial blood flow was significantly increased in patients who received nicardipine as compared with patients who did not receive nicardipine and did not have vasospasm, both at 10 min (171.2 +/- 16.2 vs. 124.3 +/- 11.9%, p < 0.05) and at 20 min (176.5 +/- 17.6 vs. 130.2 +/- 11.2%, p < 0.05) after anastomosing. Mean blood pressure was significantly reduced without causing hypotensive symptoms in patients who received nicardipine as compared with patients who did not receive nicardipine and did not have vasospasm. Our study suggests that ultrasonic Doppler flowmetry is useful for diagnosing vasospasm in patients undergoing the creation of AV fistulas and that nicardipine may be effective in preventing vasospasm safely.

Adult↗

Striatal glucose metabolism and [18F]fluorodopa uptake in a patient with tumor-induced hemiparkinsonism.

We studied a patient with a falx meningioma in the right supplementary motor area and a left-sided hemiparkinsonism that resolved after the tumor was removed. Because there was no evidence of distortion of the basal ganglia and midbrain by the tumor on neuroradiological examination, the possible mechanism of parkinsonism is an impairment of the basal ganglia output to the supplementary motor area. Positron emission tomography scans with 2-[18F]fluoro-2-doxy-D-glucose and 6-L-[18F]fluorodopa were performed to measure regional cerebral glucose metabolism and striatal dopamine metabolism, respectively. Regional cerebral glucose metabolism was decreased in the striatum of the side of the lesion, although dopamine metabolism was normal. These data suggest that the tumor may have impaired synaptic function of the striatum as a whole, giving rise to contralateral hemiparkinsonism without an impairment of the presynaptic dopaminergic nerve terminals in the striatum.

Blood Glucose↗

Particle size effect of metastable calcium phosphates on crushing strength of self-setting bioactive calcium phosphate cement.

The resistance to crushing after a self-setting bioactive calcium phosphate cement, consisting of various particle sizes of tetracalcium phosphate (TECP), dicalcium phosphate dihydrate (DCPD) and hydroxyapatite (HAP), had hardened was tested after setting at 37 degrees C, 100% RH. X-ray diffraction suggested that the cement containing fine particles of DCPD and TECP was completely transformed to HAP, but that containing larger particles was not. Since particle size of both DCPD and TECP affected the dissolution rate, the crystal growth of HAP during cement formation depended on the specific surface area (Sw) of the raw materials. The crushing strength of the cement after hardening increased with an increase of its Sw.

Bone Cements↗

[Stimulus time dependence of cerebral blood flow response to photic stimulation].

The time dependency of rCBF response to photic stimulation in the primary visual cortices was studied using H215O bolus-injection and PET. The subjects consisted of 5 normal volunteers aged from 25 to 40 years old. Their regional CBF was measured at 2 min and 7 min after the start of photic stimulation (frequency, 10 Hz). The percentage increases of rCBF were 19.6 +/- 7.9% (mean +/- SD, range: 8.9-27.6%) in the primary visual cortex on the left side and 23.2 +/- 13.6% (2.5-35.8%) on the right side at 2 min, respectively, while, in comparison, they were 25.3 +/- 20.0% (1.8-49.7%) on the left side and 25.3 +/- 16.4% (3.5-44.5%) on the right side at 7 min, respectively. No significant difference was found in the rCBF responses between at 2 min and 7 min. Therefore, the taming effect does not need to be considered when carrying out a photic stimulation study.

Adult↗

A novel skeletal drug delivery system using self-setting bioactive glass bone cement. IV: Cephalexin release from cement containing polymer-coated bulk powder.

A novel device consisting of Eudragit-coated cephalexin as a model drug and a self-setting bioactive cement based upon CaO-SiO2-P2O5 glass was investigated. The glass cement hardened within 5 min of mixing with a phosphate buffer. After setting, in vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 2 weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite and decreased in volume by about 5% during drug release in SBF. Consequently, 30% of the loaded drug was initially released from the homogeneous cement system, and thereafter it was released more slowly. Since the heterogeneous system consisting of the cement and a 50% polymer coated, drug-loaded pellet avoided this drug's burst, the drug was released over a longer period than that in the homogeneous system. The heterogeneous system released the polymer-coated drug very slowly, because it completely avoided the initial burst, and sustained the release over a long period.

Biocompatible Materials↗

[Difference in the distribution of 123I-IMP and 99mTc-HMPAO in the striatum--comparison with 15O-PET].

Brain perfusion SPECT studies of 123I-IMP and 99mTc-HMPAO were performed in 10 patients with various brain disorders and the difference in the distribution of 123I-IMP and 99mTc-HMPAO in the cortices and striatum was compared with the cerebral blood flow by 15O-PET method. The ratios of the radioactivity in 14 ROIs of the cortices, striatum and cerebellum to that of the reference region or the right frontal cortex were compared among the 3 studies. The coefficient variance between 123I-IMP and PET was 0.71 and that between 99mTc-HMPAO and PET was 0.74 in the regions excluding the striatum. The striatal activity ratio in 123I-IMP was slightly less than those in 99mTc-HMPAO and PET which were close to each other. The visual activity in the striatum in 123I-IMP was also slightly less than those in 99mTc-HMPAO and PET. All the striatal lesions of decreased perfusion diagnosed by PET were observed in 123I-IMP, however 2 lesions were missed in 99mTc-HMPAO. This seems to be relevant to the difference in the distribution of 123I-IMP and 99mTc-HMPAO.

Adolescent↗

[Leptomeningeal abnormality on Gd-DTPA enhanced MRI in a case of SLE presenting diffuse organic brain syndrome].

Involvement of the central nervous system associated with SLE (CNS lupus) is not rare. Two types of CNS lupus are noted clinically; one group manifesting focal neurological symptoms and another group showing mental symptoms. Though it is well known that neurological symptoms are caused by arteritis and thrombus, pathophysiological mechanisms leading to mental symptoms remain obscure and there is no established clinical evidence responsible for these symptoms. A 41-year-old woman was confused and her attention was markedly impaired. Her mental symptoms consisted of disorientation, restlessness, euphoria and emotional incontinence. There were neither focal neurological signs nor meningeal signs. Cerebrospinal fluid (CSF) examination showed increased number of polymorphonuclear cells and permeability of the blood-brain barrier, calculated based on the CSF/plasma protein ratio, was also elevated. Repeated bacteriological examinations revealed to be negative. Gd-DTPA MRI demonstrated diffuse enhancement of the cerebral leptomeninges. Methylprednisolone pulse therapy ameliorated her mental deterioration effectively, and subsequently the leptomeningeal enhancement with Gd-DTPA MRI disappeared in parallel. These radiological and laboratory findings suggest that SLE itself causes inflammation of vessels in the leptomeninges and adjacent cerebral cortex. We consider mental symptoms associated with SLE may be caused, at least in part, by this mechanism. To our knowledge, we could not find similar reports in the literature. Gd-DTPA enhanced MRI seems to be of clinical use for making diagnosis, evaluating clinical activity and understanding of CNS lupus.

Adult↗