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Biomedical subjects

J Minamikawa

Publications and source records attributed to J Minamikawa.

At least 19 recordsLinked to original sources

NaBH4 in N-methylpyrrolidone: a safe alternative for hydride displacement reaction.

Enhanced reactivity of NaBH4 was observed as a solution in N-methylpyrrolidone (NMP). Thus, a simple protocol for debromination of alkyl bromide and sulfonate is devised with NMP as a key solvent. Also described is a new mixed borohydride system, NaBH4-LiOTf-NMP, which works as an alternative to NaBH3CN for the SN2 type displacement. No reports have ever revealed usefulness of NMP in borohydride reduction.

Borohydrides↗

An efficient conversion of 5-nitroisatin into 5-nitroindole derivative.

Our process research on OPC-35564 revealed that a mixed borohydride reducing agent (ZrCl4/NaBH4) in DME (Itsuno system) afforded a rapid and direct conversion of N-alkyl-nitroisatin into nitroindole nucleus. Comparison with other reducing agents indicated the superiority of the present system and the key function of ZrCl4. For the manipulation of base-labile isatin, a useful procedure for its N-alkylation using Cu2CO3 is also presented.

Alkylation↗

Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes.

There have been increasing evidences that thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, may have some antiatherogenic actions. We have previously reported that troglitazone has a potent inhibitory effect on common carotid arterial intima-media thickness (IMT) in subjects with type 2 diabetes. However, some studies suggested a possibility that PPARgamma activators may have protoatherogenic actions, raising concern about their detrimental effects in diabetic subjects. In the present study, we investigated the effect of treatment with pioglitazone, another PPARgamma agonist, on IMT in a total of 106 Japanese subjects with type 2 diabetes. Pioglitazone (30 mg daily) was administered for 6 months in 53 patients. Compared to control group (n = 53), the group given pioglitazone showed a significant decrease in IMT as early as 3 months after the administration. The decrease in IMT was also found after 6 months (IMT change: -0.084[SE 0.023] mm vs. control 0.022[SE 0.006] mm, P < 0.001), although the difference between those after 3 and 6 months did not reach any statistical significance. These findings indicate that thiazolidinediones cause an inhibition of early atherosclerotic process PPARgamma activation.

Arteriosclerosis↗

Modulation of the Cs2CO3-promoted catalytic amination by a crown ether.

The catalytic addition of 18-Crown-6 in some Cs2CO3-promoted amination of triflates and bromides was beneficial to improve sluggish reaction with suppression of the unwanted side products. The protocol was useful for the preparation of chlorinated aryl piperazines from phenol derivatives.

Amination↗

Beneficial effect of cesium salts on Pd-catalyzed hydroxycarbonylation.

A Pd(0)-catalyzed hydroxycarbonylation of the aryl bromide was effectively carried out in the presence of some Cs salts such as cesium carbonate, cesium bicarbonate, and cesium acetate in wet DMF solution. For the understanding of their function, an oxy-coordinated intermediate arising from a Cs oxygen-Pd interaction has been postulated, which is likely to be responsible for related Cs assisted catalytic processes.

Bromides↗

Decrease in carotid intima-media thickness after 1-year therapy with etidronate for osteopenia associated with type 2 diabetes.

It has been suggested that bisphosphonates may have some antiatherogenic actions in experimental animals or in vitro, but their effects on the atherogenic process in humans has not been reported. In the present study the effect of etidronate treatment on carotid arterial intima-media thickness was prospectively examined in 57 subjects with type 2 diabetes associated with osteopenia. After 1 yr of therapy with cyclical etidronate (200 mg/day for 2 weeks every 3 months), intima-media thickness showed a decrease (mean +/- SE, 0.038 +/- 0.011 mm), which was significantly different from a change in 57 control subjects (0.023 +/- 0.015 mm; P < 0.005). Cardiovascular parameters were not changed after etidronate treatment. These findings suggest that etidronate in clinical dosage may have an antiatherogenic action, at least in type 2 diabetes, although its mechanisms remain to be elucidated.

Bone Diseases, Metabolic↗

Effect of calcium channel blocker amlodipine on the intimal-medial thickness of carotid arterial wall in type 2 diabetes.

Although several reports have suggested that calcium channel blockers may inhibit progression of atherosclerosis in animals, it is still controversial whether they have any clinically significant antiatherogenic action in humans. The measurement of intimal-medial thickness (IMT) of the common carotid artery by B-mode ultrasound technique has been recognized as a powerful and noninvasive method to evaluate early atherosclerotic lesions. We investigated the effect of treatment with amlodipine, a powerful calcium channel blocker, on IMT. Twenty-two hypertensive patients with type 2 diabetes were enrolled in a prospective open study. An amlodipine group (amlodipine, 5 mg; n = 11) and a control group receiving angiotensin-converting enzyme inhibitors (n = 11) were studied before and 6 months after treatment. Amlodipine treatment caused a significant decrease in IMT compared with control (-0.052 +/- 0.017 vs. 0.011 +/- 0.021 mm; p < 0.05). Although the exact mechanisms remain to be elucidated, our preliminary result suggests that amlodipine has an antiatherogenic action in type 2 diabetes.

Aged↗

Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes.

There is increasing evidence that insulin resistance may be causally related to atherosclerosis. The measurement of common carotid arterial intimal and medial complex thickness (IMT) by B-mode ultrasound technique has been recognized as a powerful and non-invasive method to evaluate early atherosclerotic lesions. We investigated the effect of treatment with troglitazone, an insulin sensitizer, on IMT in a total of 135 Japanese subjects with type 2 diabetes. Troglitazone (400 mg daily) was administered for 6 months in 57 patients. Compared to control group (n = 78), the group given troglitazone showed a significant decrease in IMT as early as 3 months after the administration (IMT change: -0.080[SE 0.016] mm vs. control 0.027[SE 0.007] mm, P < 0.001). The decrease in IMT was also found after 6 months, although further decrease was not observed. Both HbA1c and postprandial serum triglycerides were decreased after troglitazone, but there was no statistically significant relation between a decrease in IMT and those in HbA1c or postprandial triglycerides. These findings indicate that troglitazone has a potent inhibitory effect on progression of early atherosclerotic lesions probably through the decreased insulin resistance in type 2 diabetes.

Carotid Arteries↗

Low bone mineral density in a case of mosaicism Klinefelter syndrome: rapid response to testosterone therapy.

Male hypogonadism has been recognized as one of the major causes of secondary osteoporosis, but most cases seem to be left undiagnosed. We report a 54-year-old case of mosaicism Klinefelter syndrome lacking typical clinical features such as tall stature or low intelligence, who was found to have marked decrease in lumbar bone mineral density (BMD: 0.686 g/cm2) during treatment of diabetes mellitus. In investigation for etiologies of secondary osteoporosis, he was diagnosed as having mosaicism Klinefelter syndrome (XXY/XY/XX). Although he was infertile, he lacked typical clinical features of Klinefelter syndrome. Testosterone replacement was started, which resulted in an increase in BMD up to 0.712 g/cm2 two months after the initiation of therapy. The fact that BMD increased shortly after the initiation of testosterone replacement therapy in the present case supported a beneficial effect of testosterone on BMD, as recently suggested in idiopathic hypogonadotropic hypogonadism. Although the present case was diagnosed as having mosaicism Klinefelter syndrome by investigating etiologies for osteoporosis, it may be stressed that male hypogonadism, in general, should be adequately suspected in the presence of infertility and from the findings of physical examination.

Bone Density↗

Clinical use of mechanical detachable coils for dural arteriovenous fistula.

Seven dural arteriovenous fistulas were successfully embolized with mechanical detachable coils. Two lesions were located in the transverse-sigmoid sinus, four in the cavernous sinus, and one in the marginal sinus. All lesions were completely occluded on postembolization angiography. No recurrent symptoms appeared during a mean follow-up period of 11 months. Owing to the length and retrievability of the mechanical detachable coils, embolization was quicker and safer, and coils were packed more densely, than is possible with conventional coils. Coil migration was avoided because coils of the appropriate size were chosen before they were placed.

Aged↗

The effects of atrial natriuretic peptide on brain edema, intracranial pressure and cerebral energy metabolism in rat congenital hydrocephalus.

Atrial natriuretic peptide (ANP) regulates fluid and electrolyte homeostasis in the central nervous system. In this study, we evaluated the effects of ANP on brain edema, intracranial pressure (ICP) and cerebral energy metabolism in congenital hydrocephalus in rats. Brain edema, indicated by the longitudinal relaxation time (T1), was evaluated by 1H-magnetic resonance imaging (MRI). The ICP was monitored with a miniature pressure-transducer with telemetric system. Cerebral energy metabolism, indicated by PCr/Pi ratio, was measured by 31P-magnetic resonance spectroscopy (MRS). The rats were given 10 microliters of ANP in the left cerebral ventricle. Three different concentrations of ANP were given; 0.2 (group I), 2.0 (group II) and 20.0 (group III) micrograms/10 microliters, respectively. 10 microliters of saline was injected into the ventricle of the control group rats. There were no significant changes of ICP, T1 value and PCr/Pi ratio among the control group, group I and group II. In group III, in contrast, ICP decreased significantly at 20 minutes after ANP administration and stayed at this ICP level for 60 minutes. The T1 value decreased and PCr/Pi ratio increased 30 minutes after ANP administration. This study revealed that intraventricularly administered ANP could decrease ICP, reduce brain edema and improve the cerebral energy metabolism in rats with congenital hydrocephalus.

Animals↗

[Delayed cerebral dysautoregulation after recirculation of cerebral ischemia].

Sequential changes of cerebral autoregulation were studied in 20 cats after recirculation of cerebral ischemia. The cerebral autoregulation was evaluated by autoregulation index (A.I.), calculating % delta cerebral blood flow (CBF)/delta cerebral perfusion pressure (CPP), with changing the mean arterial blood pressure (MABP) within 80-130 mmHg. Duration of ischemic insult was 15 min after disappearance of direct cortical response (DCR). Following recovery of cerebral circulation, MABP, CBF and intracranial pressure (ICP) were observed sequentially for at least 48 hours. In 6 of 20 cats the autoregulation was disturbed early after recirculation, and the ICP was increased, resulting in no cerebral blood flow (early deteriorated group). In the other 14 cats the autoregulation was restored immediately, but in 7 of the 14 cats it was disturbed again after 24 hours following recirculation (delayed deteriorated group), finally the ICP was elevated and the CBF became 0 as same as early deteriorated group. In another 7 cats it was not disturbed until 5 days. The changes in CBF following insult were five patterns. These were classified into type A (Gradual decrease), type B (Transient increase), type C (Constant maintenance), type D (Relatively rapid decrease) and type E (Rapid decrease). The delayed cerebral dysautoregulation occurred in the types except for type A and type E. These results suggested there was close relation between delayed dysautoregulation and delayed neuronal dysfunction that we reported previously. Moreover, we considered the delayed dysautoregulation could be speculated from the value of ICP/CBF immediately after recirculation and the pattern of the changes in CBF during ischemic insult.

Animals↗

[Experimental study on pathophysiology and treatment of congenital hydrocephalus evaluated by magnetic resonance imaging and magnetic resonance spectroscopy].

I. Experimental Study on Pathophysiology of Congenital Hydrocephalus It is well known that the major pathogenic mechanism of hydrocephalus is disturbance in cerebrospinal fluid (CSF) circulation. For this reason, many studies on hydrocephalus were intended from the viewpoint of CSF circulation both experimentally and clinically. However, few studies have yet been done on the correlation between the morphological changes and the changes in cerebral energy metabolism in hydrocephalus in vivo. So, in this study, the correlation between the morphological changes and the changes in cerebral energy metabolism in congenital hydrocephalic rats was evaluated experimentally. The morphological changes were estimated by using magnetic resonance imaging (MRI), and the longitudinal relaxation time (T1) of brain tissue at parietal area was also measured. The cerebral energy metabolism was evaluated by using 31P magnetic resonance spectroscopy (MRS) method, and cerebral phospholipid membrane metabolism was also evaluated by using 31P-MRS method. The region of interest (ROI) giving rise to the 31P spectra was placed at fore-brain and parietal area. The PCr/Pi ratio was used as the chosen indicator of cellular bioenergetic status. The PME/beta-ATP ratio and PDE/beta-ATP ratio were used as the chosen indicator of cerebral phospholipid membrane metabolism. The intracellular pH was also evaluated by using 31P-MRS method. Fifty congenital hydrocephalic rats of the HTX strain were used. The animals were divided into two groups--non-hydrocephalic group (n = 15) and hydrocephalic group (n = 35)--. The rats of hydrocephalic group were subdivided into three smaller groups according to the degree of hydrocephalus--mild (n = 15), moderate (n = 10) and severe (n = 10)--, which was estimated by using the cerebro-ventricular ratio (CVR) in coronal section of MRI. Experimental results were as follows: 1) The T1 values in rats of mild, moderate and severe hydrocephalic groups showed significant elongation in comparison with the value in non-hydrocephalic group (p less than 0.01), which indicated the expansion of interstitial edema in cerebral cortex. 2) The correlation between the T1 value and the CVR was evaluated and the correlation coefficient (r) was 0.932 which indicated high correlation. 3) The PCr/Pi ratios in rats of mild, moderate and severe hydrocephalic groups were decreased significantly in comparison with the value in non-hydrocephalic group (p less than 0.01), which demonstrated the disturbance of cerebral energy metabolism in congenital hydrocephalic rats. 4) The PCr/Pi ratio seemed to give the indicative data concerning the prognosis of congenital hydrocephalus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A case of treatment-related leukoencephalopathy: sequential MRI, CT and PET findings.

A case of treatment-related leukoencephalopathy is presented. A patient with medulloblastoma was postoperatively treated with craniospinal axis irradiation. One month after irradiation, weekly intrathecal administration of methotrexate was performed 4 times to treat cerebrospinal fluid dissemination of the tumor. Two months after the initiation of intrathecal chemotherapy, the patient became somnolent and developed decerebrate posturing. Magnetic resonance imaging showed diffuse leukoencephalopathy. Positron emission tomography revealed a diffuse decrease in glucose uptake in the deep white matter. Auditory evoked potential also showed diffuse abnormalities, not only in the cerebrum, but also in the brain stem. High dose intravenous leucovorin rescue was attempted without any neurologic improvement.

Blood Proteins↗