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Biomedical subjects

Junichi Takada

Publications and source records attributed to Junichi Takada.

At least 19 recordsLinked to original sources

Underutilization of antiosteoporotic drugs by orthopedic surgeons for prevention of a secondary osteoporotic fracture.

BACKGROUND: Despite the availability of effective treatment and well-publicized treatment guidelines for preventing osteoporotic fractures, there are significant gaps in implementing the recommendations, and it is unknown how many patients are treated for prevention of secondary osteoporotic fractures. In this study, we investigate what percentage of osteoporosis patients were treated with antiosteoporotic drugs after osteoporotic fractures of the hip, wrist, and proximal humerus, and we discuss here the need for improvement in the treatment of osteoporosis following fracture. METHODS: We studied 422 patients with osteoporotic fractures, 91 men and 331 women, with an average age of 77.1 years (range, 52-102 years). The 422 cases consisted of 299 hip fractures, 97 distal radius fractures, and 26 proximal humerus fractures. All patients underwent surgical intervention. The variables were examined to ascertain whether osteoporosis patients were medicated with antiosteoporotic drugs at postfracture. RESULTS: Fifty-five (13%) of the 422 patients received antiosteoporotic medication at postfracture. Pharmaceutical treatment was given in 44 cases (14.7%) of hip fractures, 8 cases (8.2%) of distal radius fractures, and 3 cases (11.5%) of proximal humerus fractures. Thirty-one (7.3% of total) of the 55 patients were taking the same medication pre- and postfracture. Seven (1.7%) of the 55 were administered a different drug compared to before the fracture, and 17 (4%) started to take an antiosteoporotic drug for the first time subsequent to the fracture. CONCLUSIONS: The present rate of treatment is insufficient given the high risk of secondary fractures and the availability of appropriate drugs that would reduce that risk.

Aged↗

Orthodontic treatment in a patient with Van der Woude's syndrome.

Van der Woude's syndrome (VDW; #OMIM 119300) is an autosomal dominant disease characterized by cleft lip and/or palate and lower lip pit (fistula). The precise skeletal characteristics are unclear, and there have been no case reports of orthodontic treatment of patients with VDW. The Japanese girl whose treatment is reported here had VDW, including bilateral cleft lip and palate and bilateral symmetric lower lip pits. Orthodontic treatment started when she was just 3 years old, with a removable maxillary expansion appliance, followed by an edgewise multibracket appliance in both arches. Retention began at 11 years of age, and a secondary bone graft was performed for the alveolar cleft. She received prosthetic treatment and achieved a desirable occlusion at 18 years of age. Early intervention helped achieve a satisfactory treatment result for our patient. In contrast, her mother also had VDW, with a severe Class III skeletal pattern, but she had not been treated orthodontically; she had an anterior and lateral crossbite even after prosthetic treatment. The pretreatment characteristics of 4 other subjects with VDW are discussed; they show wide variations in the sizes of the maxilla and the mandible, suggesting that a common skeletal pattern is not generally seen in VDW.

Adult↗

Valsartan improves the lower limit of cerebral autoregulation in rats.

The effects of angiotensin II type 1 receptor blockers (ARBs) on cerebral blood flow (CBF) autoregulation have not been fully clarified. Thus, we examined the acute effect of valsartan, the most selective ARB, on CBF autoregulation in spontaneously hypertensive rats. Intravenous administration of valsartan (0.3 mg/kg) reduced the mean arterial pressure (MAP) from 184+/-5 (mean+/-SEM) to 174+/-5 mmHg (p<0.001) without affecting CBF as measured by laser-Doppler flowmetry. The lower limit of CBF autoregulation (the MAP at which the CBF was 80% of the baseline value) in the valsartan-treated group (122+/-3 mmHg) was significantly lower than that in the control group (135+/-4 mmHg, p<0.05). Reverse transcribed-polymerase chain reaction and immunohistochemical staining demonstrated that both angiotensin II type 2 receptors and angiotensin II type 1 receptors (AT1Rs) were expressed in endothelial and smooth muscle cells of the rat cerebral arteries. These results suggest that specific inhibition of AT1Rs in the cerebral circulation causes the leftward shift of the lower limit of autoregulation.

Angiotensin II Type 1 Receptor Blockers↗

[Application of anti-resorptive drugs for the treatment of osteoporosis].

The applications of anti-resorptive drugs for the treatment of osteoporosis were reviewed. The aging, low bone mineral density, increased bone turnover, and prevalent fracture were risk factors for new fracture. Bisphosphonates (alendronate and risedronate) and raloxifene showed a significant reduction in relative risk for vertebral fractures. On the other hand, alendronate and risedronate were the only two therapies that had a significant pooled treatment effects on nonvertebral fracture reduction. Hip fractures in Japan increase in the age of 70 years and over. This etiology indicates that bisphosphonate might be suitable for the patients who were 70 years of age and over. There was no significant difference between alendronate and risedronate in the efficacy of the decrease of bone resorption marker.

Aged↗

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. DPD (total, free)].

Urinary deoxypyridinoline (DPD) shows a high specificity for bone, and the measurement of DPD is not influenced by newly collagens and dietary intake. The measurement of free DPD is available by Japanese health insurance. Free DPD excretion above the upper limit of the premenopausal range was associated with increased hip fracture and osteoporotic fracture risk with approximately 2-folds. Total DPD is good predictor of change bone mineral density (BMD) in bone antiresorptive drugs, however, free DPD is inferior to type I -collagen N-telopeptide (NTX).

Amino Acids↗

[Prospects of treatment using interferon for bone diseases].

Osteoblasts and osteoclasts produce a variety of cytokines to maintain bone homeostasis. One of the most important cytokines, receptor activator of nuclear factor-IkappaB ligand (RANKL), is essential for osteoclastogenesis. Recently, it was shown that activated T cells promote osteoclastogenesis through RANKL expression and also negatively affect osteoclastogenesis through interferon (IFN)-gamma production. Additionally, it was revealed that IFN-beta was involved in osteoclast regulation by signaling cross-talk with RANKL and that it contributed to the maintenance of normal bone mass. These studies indicate that there are complex regulatory interactions between bone-remodeling cells and immune cells, which depend on the balance between RANKL and IFN. Thus, the interaction between T cells and bone cells could be physiologically critical for the maintenance of normal bone metabolism, and IFN might be an attractive cytokine for use in therapy for bone disease in pathological bone resorptive conditions such as rheumatoid arthritis, osteoporosis, osteomyelitis and bone metastasis of cancers.

Bone Diseases, Metabolic↗

[Adequate treatment with bisphosphonates for senile osteoporosis].

The characteristics of senile osteoporosis are as follows. (1) Bone turnover is not always decrease in senile osteoporosis. (2) Senile patients have urgent fracture risk, such as aging, prevalent fracture(s), low bone mass, and increasing bone turnover. (3) Most of patients are insufficient of calcium and vitamin D. The important things of the treatment for senile osteoporosis with bisphosphonates are (1) to take calcium and vitamin D sufficiently to avoid the excess secretion of parathyroid hormone, (2) to pay attention gastro-esophageal reflux disease, especially the patients with spinal deformity, and (3) to adhere the patient with treatment.

Adult↗

Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia.

BACKGROUND: Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. METHODS AND RESULTS: Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or beta-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1beta, or tissue necrosis factor-alpha in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623+/-2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1beta and augmented tissue necrosis factor-alpha. CONCLUSIONS: Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.

Animals↗

Efficacy of cementless total hip arthroplasty in patients on long-term hemodialysis.

We retrospectively reviewed 11 hip arthroplasties in 7 patients receiving long-term (15 years) hemodialysis for chronic renal failure. Osteonecrosis of the femoral head, osteoarthritis, and amyloid arthropathies were treated by total hip arthroplasty (THA) or bipolar hemiarthroplasty (BHA) using cementless anatomic medullary locking stem. The average follow-up period was 8 years and 3 months (range, 3-13 years). The D'Aubigne and Postel hip score was restored to 14.5 postoperatively from 7.7 preoperatively. All femoral cementless components achieved bone-ingrown fixation. Although 1 BHA resulted in central migration, there was no loosening of the cementless acetabular component. We are encouraged by the predictable long-term stability of the bone-implant interface achieved by cementless fixation with an extensively coated implant. Cementless THA remains a useful treatment option for patients on long-term hemodialysis.

Adult↗

Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase.

BACKGROUND: Recent evidence has suggested that reactive oxygen species are important signaling molecules in vascular cells and play a pivotal role in the development of vascular diseases. The activity of NAD(P)H oxidase has been identified as the major source of reactive oxygen species in vascular endothelial cells. However, the precise molecular structure and the mechanism of activation of the oxidase have remained poorly understood. METHODS AND RESULTS: Here, we investigated the molecular identities and the superoxide-producing activity of endothelial NAD(P)H oxidase. We found that Nox4, a homologue of gp91phox/Nox2, was abundantly expressed in endothelial cells. The expression of Nox4 in endothelial cells markedly exceeded that of other Nox proteins, including gp91phox/Nox2, and was affected by cell growth. Using electron spin resonance and chemiluminescence, we measured the superoxide production and found that the endothelial membranes had an NAD(P)H-dependent superoxide-producing activity comparable to that of the neutrophil membranes, whereas the activity was not enhanced by the 2 recombinant proteins p47phox and p67phox, in contrast to that of the neutrophil membranes. Downregulation of Nox4 by an antisense oligonucleotide reduced superoxide production in endothelial cells in vivo and in vitro. CONCLUSIONS: These findings suggest that Nox4 may function as the major catalytic component of an endothelial NAD(P)H oxidase.

Animals↗

The serum level of bone-specific alkaline phosphatase activity is associated with aortic calcification in osteoporosis patients.

It has been suggested that there are several possible linkages between vascular calcification and osteoporosis. In addition, the processes of vascular calcification may have a common etiology with bone formation. Thus, we hypothesized that the serum levels of bone metabolic markers would be different between osteoporosis patients with and without vascular calcification. In this study, we showed that the serum level of bone-specific alkaline phosphatase activity in osteoporosis patients with abdominal aortic calcification had a higher value than in those without the calcification. On the other hand, there were no significant differences in the urine levels of type I collagen cross-linked N-telopeptides (a bone resorption marker), or in the serum levels of intact osteocalcin, Ca, and P. Bone-specific alkaline phosphatase is the most important marker for osteoblast differentiation; furthermore, the serum level of its activity may reflect the process of calcification of the aorta in osteoporosis patients.

Aged↗

Predictive factors for vascularized iliac bone graft for nontraumatic osteonecrosis of the femoral head.

We reviewed the results of 35 operations performed on 29 patients with osteonecrosis of the femoral head in which a pedicle iliac bone was utilized. The average age was 35 years (17-62). There were 28 patients of stage 2 and 7 of stage 3; there were 17 type C-1 hips and 18 type C-2 hips. The pedicle bone was inserted in the anterolateral direction of the femoral head. The average follow-up period was 8 years and 7 months. Collapse of the femoral head occurred in 19 hip joints. Although 16 of 28 stage 2 hips showed collapse, all 7 stage 3 hips resulted in collapse. Thirteen of 17 hips did not show collapse in patients with type C-1 necrosis, whereas 15 of 18 hips developed collapse in patients with type C-2 necrosis. When the bone graft was inserted in the anterolateral direction of the femoral head, incidence of collapse was reduced. These results indicate that deep circumflex iliac pedicle bone graft may be indicated for stage 2 type C-1 necrosis, and that the penetration of the graft into the anterolateral aspect of the lesion is essential for the procedure to succeed.

Adolescent↗

Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats.

Monocyte chemoattractant protein-1 (MCP-1) is expressed in the ischemic cortex after focal brain ischemia and appears to exacerbate ischemic damage. The authors examined the effect of gene transfer of dominant negative MCP-1, called 7ND, 90 minutes after induction of focal brain ischemia in hypertensive rats. Adenoviral vectors encoding mutant MCP-1 (Ad7ND; n = 11), or Escherichia coli beta-galactosidase (AdlacZ; n = 17) as control were injected into the lateral ventricle of male spontaneously hypertensive rats. Both AdlacZ (n = 12) and Ad7ND (n = 6) administration provided transgene expression as early as 6 hours after injection and the expression further increased on day 1, followed by a sustained detection on day 5. Five days after ischemia, infarct volume (75 +/- 13 mm, n = 5, mean +/- SD) significantly reduced to 72% of control (104 +/- 22 mm3, n = 5, P < 0.05) by 7ND gene transfer. Numbers of leukocytes in the vessels (48.3 +/- 32.9/cm2) and macrophage/monocyte infiltration (475.2 +/- 125.5/mm2) of the infarct area in the Ad7ND group were significantly less than those measured in the AdlacZ group (143.8 +/- 72.1/cm2 and 671.8 +/- 125.5/mm2, P < 0.05, respectively). In summary, the postischemic gene transfer of dominant negative MCP-1 attenuated the infarct volume and infiltration of inflammatory cells, suggesting potential usefulness of the anti-MCP-1 gene therapy.

Adenoviridae↗