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Biomedical subjects

K Shiizaki

Publications and source records attributed to K Shiizaki.

7 recordsLinked to original sources
PubMed2006

Direct maxacalcitol injection into hyperplastic parathyroids improves skeletal changes in secondary hyperparathyroidism.

Direct maxacalcitol (OCT) injection into a parathyroid gland (PTG) ameliorates several important etiologic factors of resistance to medical treatments for secondary hyperparathyroidism (s-HPT): the upregulations of vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in PTGs and the regression of PTG hyperplasia by the induction of apoptosis. In this study, we evaluated the bone histomorphology on the basis of maintaining these effects in advanced s-HPT. Five/six nephrectomized Sprague-Dawley rats were fed a high-phosphorus and low-calcium diet for 8 weeks. These rats were divided into four treatment groups: (1) basic uremic (at the baseline), (2) direct OCT single injection into PTGs (DI-OCT) followed by OCT intravenous administration for 4 weeks (IV-OCT), (3) direct vehicle injection and IV-OCT, and (4) no treatment for an additional 4 weeks. The effects of these treatments on serum intact-parathyroid hormone (PTH) level, PTG weight, VDR and CaSR expression levels in PTGs, and bone histomorphometric parameters were investigated. In the DI-OCT+IV-OCT group, the significant decrease in serum intact-PTH level was maintained by the following IV-OCT. A significant decrease in PTG weight and the upregulations of VDR and CaSR expression levels in PTGs were also observed. Bone histomorphometric analysis showed significant improvements in osteitis fibrosa in both cancellous and cortical bones. However, these findings were not observed in the other groups. These results suggest that osteitis fibrosa caused by advanced s-HPT can be successfully reversed by a control of PTH at an appropriate level through the improvement of PTG hyperplasia as induced by DI-OCT+IV-OCT.

Animals↗
PubMed2006

Direct injection of calcitriol or its analog into hyperplastic parathyroid glands induces apoptosis of parathyroid cells.

Hyperplasia of the parathyroid gland (PTG) is associated not only with excessive secretion of parathyroid hormone (PTH) but also with changes in the parathyroid cell (PTC) characteristics (i.e. hyperproliferative activity, and low contents of vitamin D and calcium-sensing receptors). Control of PTG hyperplasia is most important in the management of secondary hyperparathyroidism, but the advanced stage of hyperplasia is considered irreversible. In the present study, dialysis patients with PTG hyperplasia underwent direct injection of calcitriol or maxacalcitol (OCT) into the PTG. Ultrasonography showed that this treatment had significantly reduced PTG volume and tissue analysis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method and DNA electrophoresis indicated that cellular apoptosis had been induced. The mechanism of apoptosis was evaluated in detail in uremic rats fed a high-phosphate diet. OCT or its vehicle was directly injected into the rats' PTGs. In the PTGs treated by OCT, there was a significantly increased number of TUNEL-positive PTCs and DNA electrophoresis revealed the characteristic ladder pattern of DNA fragmentation, both findings indicative of apoptosis. There was also a significant upregulation of both vitamin D and Ca-sensing receptors in the PTCs and a clear shift of the Ca-PTH response curve to the left and downward. None of these findings was observed in the PTGs treated by vehicle. This novel treatment is successful in causing regression of PTG hyperplasia. Thus, it is expected to significantly reduce the PTH level and ameliorate the abnormal bone turnover and mineral metabolism.

Animals↗
PubMed2001

Plasma exchange for the treatment of human T-cell lymphotropic virus type 1 associated myelopathy.

A 55-year-old man was admitted to our hospital because of myelopathy. He had a history of chronic renal failure due to polycystic kidney disease at the age of 39, being treated by hemodialysis for 9 years with several blood transfusions for the treatment of renal anemia. After cadaver renal transplantation at the age of 48, he discontinued hemodialysis. At 50 years of age, he had pulmonary tuberculosis and tuberculous arthritis of the left elbow joint. He has experienced difficulty in walking since he was 48 years old, with mild dysuria. Gait disturbance gradually aggravated after that, and urinary retention was observed. When he was 55 years old, being human T-cell lymphotropic virus type-1 (HTLV-1)-positive in the serum and cerebrospinal fluid, he was diagnosed as having HTLV-1-associated myelopathy (HAM). As active steroid therapy was unapplicable because of the history of pulmonary tuberculosis and immunosuppression for transplanted kidney, a series of plasma exchanges (PE) was performed with fresh frozen plasma as a replacement fluid. After PE, dyskinesia of the left leg and dysuria subjectively and objectively improved. These results suggest that PE seems to be one of the therapeutic tools for the treatment of HAM.

Humans↗
PubMed2001

Antinociceptive effect of U-50488H, a kappa-opioid agonist, in streptozotocin-induced diabetic mice.

We compared the antinociceptive activity of a kappa-opioid agonist, U-50488H, in streptozotocin-induced diabetic mice with that in non-diabetic mice. Subcutaneously administered U-50488H (3 and 10 mg kg(-1)) showed a more potent antinociceptive effect, as evaluated by the tail-pressure method, in diabetic mice than in non-diabetic mice. Increased antinociceptive activity of U-50488H observed in diabetic mice was also observed in mice given U-50488H intrathecally (3 and 10 microg). However, there were no differences observed between diabetic and non-diabetic mice given U-50488H intracerebroventricularly (3 and 10 microg). Although the antinociceptive effect of U-50488H (3 mg kg(-1), s.c.) in non-diabetic mice was increased by treatment with PD135158 (100 ng, i.c.v.), a cholecystokininB (CCKB) antagonist, the antinociceptive activity of U-50488H which was enhanced in diabetic mice was not influenced by PD135158. Moreover, the increased antinociceptive activity of U-50488H (3 mg kg(-1), s.c.) in diabetic mice diminished when desulfated octapeptide of cholecystokinin (3-100 ng, i.c.v.), a CCKB agonist, was administered. These results suggested that diabetic mice were selectively hyper-responsive to spinal kappa-opioid receptor-mediated antinociception. The function of the analgesia inhibitory system in which cholecystokinin is used as a transmitter might be diminished in diabetic mice.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Bioassay of phytoestrogen in herbal medicine used for postmenopausal disorder using transformed MCF-7 cells.

It is well known that plants contain substances with oestrogen activity comparable to that in animals. In animals, oestrogens are steroid hormones while plants contain oestrogen with various chemical characteristics, referred to as phytoestrogens. These especially, may be responsible for part of the effects of Chinese herbal prescriptions for postmenopausal disorders in which oestrogen deficiency is considered the primary cause. In addition, the presence or absence of oestrogen activity in herbal medicine is considered extremely important for patients in whom oestrogen administration is contraindicated. The most important action of oestrogen is the transcriptional regulation of specific genes via oestrogen receptors (ER). Therefore, we have established a highly sensitive bioassay system by placing oestrogen responsive elements (ERE) upstream to the reporter gene, and have used this assay to determine the oestrogen activity in herbal medicine. As a result, phytoestrogens were found in many Chinese herbal prescriptions for postmenopausal disorder, and some prescriptions were considered to effectively administer hormone replacement therapy (HRT). However, since oestrogen activities in most Chinese herbal prescriptions were thought to be weak, it was considered that these prescriptions improved postmenopausal disorder based on a mechanism differing from that of oestrogen replacement therapy.

Biological Assay↗
PubMed1996

[Change in argatroban concentration within the vessel wall after local administration using hydrogel-coated balloon catheter].

Acute coronary occlusion after percutaneous transluminal coronary angioplasty is one of the major problems in coronary intervention. This study evaluated the hydrogel-coated balloon delivery of argatroban to the arterial wall and argatroban persistence after angioplasty in 17 rabbits. A hydrogel-coated balloon was immersed three times in argatroban/saline solution (1 mg/ml) and inflated at 6 atm pressure for 1 min in the common carotid artery. The transfer of argatroban to the vascular wall was measured by high-performance liquid chromatography. The concentrations of argatroban at 0, 5, and 15 min after deflation were 14.8, 4.2, and 3.9 nmole/g.wet weight. The hydrogel-coated balloon catheter can deliver argatroban to the local arterial wall during balloon inflation.

Angioplasty, Balloon, Coronary↗