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M Sato

Publications and source records attributed to M Sato.

At least 37 records · Page 2Linked to original sources

Raloxifene and vitamin K2 combine to improve the femoral neck strength of ovariectomized rats.

We evaluated the skeletal effects of two osteoporosis therapies in an ovariectomized rat model, raloxifene and vitamin K2, as well as the vitamin K2 plus raloxifene (K + Ral) combination. In two studies, 6-month-old rats were ovariectomized, except for sham-ovariectomy controls (Sham), and dosed orally with vehicle, 30 mg/kg vitamin K2, 1 mg/kg raloxifene, or the combination of K + Ral for 6 weeks following surgery. Vitamin K2 had no effect on serum estrogen, low-density lipoprotein cholesterol (LDL-C), or urinary deoxypyridinoline levels, but slightly increased osteocalcin levels compared to Ovx. Raloxifene lowered total cholesterol, LDL-C, osteocalcin, and urinary deoxypyridinoline levels to below Ovx levels, while having no effect on estrogen levels. Raloxifene, but not vitamin K2, prevented ovariectomy-induced loss of bone in the distal femoral metaphysis and proximal tibial metaphysis, as did the K + Ral combination. Raloxifene, but not vitamin K2, partially prevented, loss of vertebral bone mineral density (BMD), whereas K + Ral had BMD greater than that of Ovx. Vitamin K2 increased bone formation rate to above Ovx, whereas raloxifene and K + Ral reduced bone formation rate to Sham levels. Vitamin K2 had no effect on eroded surface compared to Ovx, while raloxifene and K + Ral reduced eroded surface to Sham levels. Groups were not different in the BMD of femoral midshaft; however vitamin K2 was observed to increase periosteal mineralizing surface of the tibial shaft to above Ovx, while raloxifene reduced periosteal mineralizing surface toward Sham levels. Femoral neck strength was not different between groups, indicating no significant beneficial effect of either raloxifene or vitamin K2 at this site. However, K + Ral had reproducibly greater femoral neck strength than Ovx or Sham. Raloxifene, but not vitamin K2, partially prevented loss of lumbar vertebra strength; but K + Ral was not different from Sham or Ovx. Therefore, raloxifene and vitamin K2 had complementary effects on bone resorption and formation activities, respectively, resulting in a reproducible, significant improvement of femoral neck strength. These rat data suggest interesting therapeutic possibilities that may require clinical verification.

Administration, Oral↗

Baroreflex control of heart rate during and after propofol infusion in humans.

BACKGROUND: This study was designed to determine cardiovagal baroreflex gain during propofol infusion and to characterize its recovery profile using the pharmacological and spontaneous sequence methods in 13 healthy volunteers without cardiovascular or autonomic disorders. METHODS: After an 8- to 10-h fast and no premedication, measurements of RR intervals obtained from the electrocardiogram and non-invasive beat-to-beat systolic blood pressure (SP) were made at conscious baseline, at 60 and 120 min after induction of general anaesthesia using propofol, and at 20, 60, 120 and 180 min after emergence from anaesthesia. During propofol anaesthesia, ventilation was mechanically controlled to maintain normocapnia and calculated propofol concentration was adjusted by a TCI system at 5 microg ml(-1). Baroreflex responses were triggered by bolus i.v. injections of phenylephrine and nitroprusside to alter SP by 15-30 mm Hg. The linear portions of the baroreflex curves relating RR intervals and SP by least-square regression analysis were determined to obtain pharmacological gains. In addition, spontaneous sequence baroreflex gains were calculated from spontaneously fluctuating SP and RR intervals. RESULTS: Baseline pressor and depressor test gains before propofol anaesthesia were 29.1 (SD 14.9) and 12.5 (7.8) ms mm Hg(-1), respectively. They were significantly depressed by 65-73% during propofol infusions. Similarly, baseline up- and down-sequence baroreflex gains were 33.8 (28.9) and 27.3 (19.8) ms mm Hg(-1), respectively, and were significantly depressed by 71-87% during propofol anaesthesia. Pressor test and up-sequence baroreflex gains returned to the baseline values 20 min after emergence from propofol anaesthesia, but depressor test and down-sequence baroreflex gains did not recover until 60 min after emergence. CONCLUSIONS: We conclude that heart rate responses to both lowering and elevating blood pressure were depressed by propofol anaesthesia, and 60 min was required for their full recovery after discontinuation of propofol infusion.

Adult↗

Expression and characterization of disulfide bond use of oligomerized A2-Pancortins: extracellular matrix constituents in the developing brain.

The region-specific characteristics of the extracellular matrix are crucial for diverse functions in the brain. Pancortins/neuron-specific olfactomedin-related glycoproteins are components of the extracellular matrix. They comprise four alternatively spliced variants, Pancortin-1 to -4, which share a common portion, the B part, in the middle of their structure, have two pairs of alternatively spliced 5' regions, A1 and A2, and 3' regions, C1 and C2. Here we demonstrate that in mice, Pancortin-3 (A2-B-C1) and Pancortin-4 (A2-B-C2), which we have grouped together the A2-Pancortins, were transcribed early during the development of the brain in a region specific manner and were expressed very stably in vivo. They are N-glycosylated and secreted. Furthermore, we examined their ontogenetical expression profiles in the developing thalamus using antiserum against the common B region, since transient expressions of their mRNAs were notable there. In the developing thalami, they lasted long in oligomerized form even after the transcription of their mRNAs decreased to an undetectable level. Further analyses revealed that cysteine residues that are located in the common B part are important for homo- and hetero-oligomer formation of A2-Pancortins. When we substituted cysteine residues 45 and 47 with serine residues in that common B part, oligomerization of the A2-Pancortins was highly disturbed.

Age Factors↗

Enhancement of adenoviral gene transfer to adult rat cardiomyocytes in vivo by immobilization and ultrasound treatment of the heart.

Direct injection of adenoviral vectors into ventricular myocardium in vivo produces local transfection of cells including cardiomyocytes. The use of vectors coexpressing GFP with the gene of interest allows subsequent identification of transfected myocytes isolated from the heart some days later, and examination of their function in cell bath experiments. We have injected vectors for antisense to phospholamban, or a control virus for expression of GFP only, into adult rat heart in vivo and then removed the heart and isolated ventricular myocytes 7 days later. Brief immobilization of the ventricle during and after injection using a haemoclip increased the number of transfected rod-shaped, viable myocytes from 1.7 +/- 0.8% (n = 8) to 5.6 +/- 0.8% (n = 9). This was further increased to 13.2 +/- 1.1% (n = 8) by the application of ultrasound pulses to the site before and after injection. Phospholamban antisense increased contraction amplitude and accelerated myocyte relengthening or decline of the Ca(2+) transient in transfected myocytes, while GFP control did not. Qualitative and quantitative effects of phospholamban downregulation were comparable between in vivo and in vitro transfections. This technique will have a number of uses, including production of transfected myocytes without the problem of culture-induced changes in contractility.

Adenoviridae↗

A prospective randomized comparative study on the safety and tolerability of transnasal esophagogastroduodenoscopy.

BACKGROUND AND STUDY AIM: Transnasal esophagogastroduodenoscopy (EGD) with a small-caliber endoscope is well tolerated by patients. However, the effect of this procedure on cardiopulmonary function has not been fully investigated. The aim of this prospective, randomized study was to investigate the effect of transnasal EGD in comparison with transoral EGD on cardiopulmonary function. PATIENTS AND METHODS: The study involved 450 patients referred for diagnostic EGD. Patients were randomly assigned to one of three types of unsedated EGD (150 patients per group): transnasal EGD using a small-caliber endoscope (the "XP-N" group), transoral EGD using the same small-caliber endoscope ("XP-O" group), and transoral EGD using a conventional endoscope ("XQ" group). Systolic and diastolic blood pressure, pulse rate, and arterial oxygen saturation were monitored before, and 2, 4 and 6 minutes after intubation, and just after endoscope extubation. Gagging episodes were also counted, to determine tolerance. RESULTS: It was not possible to perform transnasal EGD in 12 patients (8.0%). A small amount of epistaxis was observed in eight (5.8%) of 138 patients who were examined successfully by transnasal EGD. Systolic and diastolic blood pressure, pulse rate, rate-pressure product (pulse rate x systolic blood pressure/100), and the drop in arterial oxygen saturation in the XQ group were significantly greater than in the XP-N and XP-O groups at each time point. In the XP-N group, these parameters were significantly lower than those in the XP-O group at 2 minutes after intubation. Of the tree groups the number of gagging episodes was significantly lower in the XP-N group. CONCLUSION: Transnasal EGD is safer than transoral EGD as it is associated with fewer adverse effects on cardiopulmonary function and is better tolerated by patients.

Adult↗

Famotidine prevents canine gastric blood flow reduction by NSAIDs.

AIM: To investigate the effect of famotidine on gastric blood flow reduction induced by diclofenac sodium, a common non-steroidal anti-inflammatory drug in Japan, using laser Doppler flowmetry in the canine stomach. METHODS: The gastric mucosal blood flow was measured by laser Doppler flowmetry in 15 healthy male beagles before and 60 min after the administration of diclofenac suppository (1.0 mg/kg) into the rectum. The examination was done in a crossover, single-blinded fashion. All dogs underwent both famotidine (0.5 mg/kg) and placebo (saline) injection simultaneously with the administration of diclofenac. In addition, the tissue concentration of prostaglandin E2 was measured. RESULTS: The blood flow decreased by 18.3 +/- 9.1% in the gastric body, by 26.3 +/- 8.1% in the antrum in the placebo group after the administration of diclofenac sodium, while the decreases seen were significantly smaller in the famotidine group: 3.2 +/- 12.6% in the gastric body and 7.9 +/- 16.5% in the antrum (P = 0.001 for the gastric body, P = 0.0034 for the antrum). Conversely, the percentage of mucosal prostaglandin E2 concentration decrease in each group did not show a significant difference. CONCLUSION: Famotidine alleviates the reduction of gastric blood flow induced by diclofenac sodium. Further, not only mucosal prostaglandins but also gastric acid may play an important role in non-steroidal anti-inflammatory drugs-induced gastric microcirculatory disturbance.

Animals↗

Neuroprotective effect of mivazerol, an alpha 2-agonist, after transient forebrain ischemia in rats.

BACKGROUND: We examined whether mivazerol, an alpha2-agonist, had neuroprotective effects after transient forebrain ischemia in rats. METHODS: Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of four groups (n=10 each): control (C, normal saline) and mivazerol 10 microg/kg (M10), 20 microg/kg (M20) and 40 microg/kg (M40) groups. Thirty minutes after drug administration, forebrain ischemia was induced with hemorrhagic hypotension and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. The neurologic outcome was evaluated 24 h, 48 h and 7 days after ischemia, followed by histologic evaluation. RESULTS: The survival rate during 7 days was significantly lower in group M40 than in groups M10 and M20 (P<0.05). The neurologic outcome was significantly better in groups M10 and M20 than in group M40 7 days after ischemia (P<0.05). The number of intact neurons in hippocampal CA1 was significantly greater in group M20 than in the other groups (P<0.05). Neuronal injury in the neocortex was significantly less in group M20 than in groups C and M40 (P<0.05). CONCLUSIONS: Our results suggest that mivazerol, up to 20 microg/kg, provides neuroprotective effects, whereas 40 microg/kg may exaggerate neuronal injury after transient forebrain ischemia in rats.

Adrenergic alpha-Agonists↗

Blood lead and erythrocyte protoporphyrin levels in association with smoking and personal hygienic behaviour among lead exposed workers.

AIMS: To investigate the effects of smoking and personal hygienic behaviour on blood lead (BPb) and free erythrocyte protoporphyrin levels (FEP) in lead exposed workers. METHODS: Subjects were 105 lead exposed male workers in a battery recycling plant during the years 2000-03. BPb and FEP were measured as part of the ongoing occupational surveillance. Each worker completed a questionnaire for assessment of smoking and four measures of personal hygienic behaviour (glove and mask use, hand and face washing before meals during working hours). RESULTS: Statistically significant decreases in mean BPb and FEP occurred during the three years. The proportion of BPb reduction in the non-smoking workers was significantly higher (mean 24.3%) than in the smoking workers (15.3%). When the workers were classified into three groups (excellent, good, and poor) based on the four personal hygienic behavioural indicators, the greatest decreases of BPb and FEP were observed in the non-smoking workers of the excellent group. CONCLUSIONS: The consistent use of protection devices and cleanliness at work appeared to contribute to the lowering of BPb and FEP. Cessation of smoking in the workplace was also of importance.

Adult↗

Selective conformal radiotherapy for arteriovenous malformation involving the spinal cord.

Radiotherapy has seldom been used in the treatment of arteriovenous malformations (AVM) involving the spinal cord because of the cord's limited radiation tolerance. A 57-year-old woman with progressive myelopathy due to AVM was treated with a selective conformal radiation therapy (55.6 Gy/20 days) on the nidus region preserving the spinal cord, drainer veins and involved bones. The drainers and symptoms were minimized at the end of treatment and disappeared over 2 years. This case illustrates the usefulness of selective conformal radiation therapy.

Arteriovenous Malformations↗

Inflammatory cytokine gene expression in different types of granulomatous lesions during asymptomatic stages of bovine paratuberculosis.

The granulomatous lesions in bovine paratuberculosis have been classified into two types, i.e., the lepromatous type and the tuberculoid type. To clarify the immunopathologic mechanisms at the site of infection, we compared inflammatory cytokine gene expression between the two types of lesions. Samples were obtained from noninfected control cows (n = 5) and naturally infected cows (n = 7) that were diagnosed by enzyme-linked immunosorbent assay (ELISA) and fecal culture test. Although none of the infected cows showed clinical signs, tuberculoid lesions were observed in five cows (tuberculoid group) and lepromatous lesions in two cows (lepromatous group). Among the cytokines examined by reverse transcription-polymerase chain reaction (RT-PCR), Th2-type cytokines interleukin-4 (IL-4) and IL-10, and Th1-type cytokine IL-2 were expressed more significantly in the lepromatous group than in the tuberculoid (P < 0.01) and noninfected groups (P < 0.05). No statistical differences were observed in the expression of interferon-gamma, IL-1 beta, TNF-alpha, and GM-CSF among lepromatous, tuberculoid, and noninfected groups. Expression of proinflammatory cytokine IL-12 mRNA, however, did not differ among the three groups; IL-18 was expressed at lower levels in the lepromatous group than in the tuberculoid group and the noninfected group (P < 0.0001). Moreover, the number of cells in which IL-18 mRNAs were detected by in situ hybridization was markedly decreased in the lepromatous group. These results indicate that the formation of lepromatous-type lesions or tuberculoid-type lesions may be influenced by alterations in Th1/Th2-type cytokine production and that IL-18 may play an important role in a Th1-to-Th2 switch in paratuberculosis.

Animals↗

Ethnoecology and conservation in protected natural areas: incorporating local knowledge in Superagui National Park management.

The majority of protected natural areas in Brazil were created in coastal areas inhabited by humans for centuries. However, legal protection has triggered a series of conflicts involving human settlements in these areas. To overcome part of these problems, ethnoecological studies have been conducted in order to discover what is known by local indigenous communities with respect to the land, its natural cycles, occurrence and abundance of animal species, and their use. This knowledge, coupled with that acquired in dealing with current situations that negatively affect the quality of life, is useful in protected natural-area planning and management. To that end, the present study proposes environmental education based on ethnoscientific methods, designed to facilitate the maintenance of sociodiversity in the Superagui National Park.

Animals↗

Efficacy and outcomes of clarithromycin treatment for pulmonary MAC disease.

SETTING: Retrospective review of patients with pulmonary Mycobacterium avium complex (MAC) disease treated with clarithromycin. OBJECTIVES: To investigate whether the short-term response to treatment predicts long-term outcomes, and to analyse what explanatory variables are associated with the efficacy and outcome of treatment. DESIGN: Sputum conversion rates in short- and long-term outcomes were evaluated for 111 patients. Respectively 9 and 10 explanatory variables were analysed for their association with both response and outcomes. RESULTS: Eighty-four patients (75.7%) showed good short-term response and 94 (82.0%) showed good long-term outcomes. Women and patients with satisfactory nutrition status showed good short-term response. Patients with small lesions and those treated for >12 months after sputum conversion showed good long-term outcomes. Patients who showed good short-term response, in the group with large lesions, showed significantly good long-term outcomes (P = 0.0382). CONCLUSION: There were differences between prognostic factors reflecting short-term response and long-term outcomes. The short-term response predicts long-term outcomes in certain groups divided by prognostic factor. To establish standard treatment for pulmonary MAC disease, it is important to determine a standardised method of evaluation of treatment taking such factors into consideration.

Adult↗

Intracellular stress transmission through actin stress fiber network in adherent vascular cells.

Intracellular stress transmission through subcellular structural components has been proposed to affect activation of localized mechano-sensing sites such as focal adhesions in adherent cells. Previous studies reported that physiological extracellular forces produced heterogeneous spatial distributions of cytoplasmic strain. However, mechanical signaling pathway involved in intracellular force transmission through basal actin stress fibers (SFs), a mechano-responsive cytoskeletal structure, remains elusive. In the present study, we investigated force balance within the basal SFs of cultured smooth muscle cells and endothelial cells by (i) removing the cell membrane and cytoplasmic constituents except for materials physically attaching to the substrate (i.e., SF-focal adhesion complexities) or (ii) dislodging either mechanically or chemically the cell processes of the cells expressing fluorescent proteins-labeled actin and focal adhesions in order, to examine stress-release-induced deformation of the basal SFs. The result showed that a removal of mechanical restrictions for SFs resulted in a decrease in the length of the remaining SFs, which means SFs bear tension. In addition, a release of the preexisting tension in a single SF was transmitted to another SF physically linked to the former, but not transmitted to the other ones physically independent of the former, suggesting that the prestress is balanced in tensed SF networks. These results support a hypothesis regarding cell structural architecture that physiological extracellular forces can produce in the basal SF network a directional intracellular stress or strain distribution. Therefore, consideration of the coexistence of the directional stretching strain along the axial direction of SFs and the heterogeneous strain in the other cytoplasmic region will be essential for understanding intracellular stress transmission in the adherent cells.

Actins↗

Evaluation of tension in actin bundle of endothelial cells based on preexisting strain and tensile properties measurements.

Actin bundles in vascular endothelial cells (ECs) play a critical role in transmitting intracellular forces between separate focal adhesion sites. However, quantitative descriptions of tension level in single actin bundles in a physiological condition are still poorly studied. Here, we evaluated magnitude of preexisting tension in a single actin bundle of ECs on the basis of measurements of its preexisting stretching strain and tensile properties. Cultured ECs expressing fluorescently-labeled actin were treated with detergents to extract acin bundles. One end of an actin bundle was then dislodged from the substrate by using a microneedle, resulting in a shortening of the actin bundle due to a release of preexisting tension. Assuming the shortened actin bundle reached its non-stress state, preexisting stretching strain was determined to be 0.24 on average. A tensile test of the dislodged single acin bundle was conducted with a pair of cantilevers to measure the force required for stretching it up to the original length, yielding an estimate of preexisting tension in the actin bundle. The magnitude of the preexisting tension, 4 nN on average, was comparable to previously reported data of the traction force generated by adherent cells at single adhesion sites to keep cell integrity. The Young's modulus of the isolated actin bundle was estimated to be approximately 300 kPa from the tensile tests together with evaluation of average diameter of the isolated actin bundle based on transmission electron microscopy. These data will contribute to better understanding of intracellular stress transmission mechanism in ECs.

Actins↗

Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus.

A detailed analysis of the differential effects of estrogen (E) compared to raloxifene (Ral), a selective estrogen receptor modulator (SERM), following estrogen receptor (ER) binding in gynecological tissues was conducted using gene microarrays, Northern blot analysis, and matrix metalloproteinase (MMP) 2 activity studies. We profiled gene expression in the uterus following acute (1 day) and prolonged daily (5 wk) treatment of E and Ral in ovariectomized rats. Estrogen regulated twice as many genes as Ral, largely those associated with catalysis and metabolism, whereas Ral induced genes associated with cell death and negative cell regulation. Follow-up studies confirmed that genes associated with matrix integrity were differentially regulated by Ral and E at various time points in uterine and vaginal tissues. Additional experiments were conducted to determine the levels of MMP2 activity in uterus explants from ovariectomized rats following 2 wk of treatment with E, Ral, or one of two additional SERMs: lasofoxifene, and levormeloxifene. Both E and lasofoxifene stimulated uterine MMP2 activity to a level twofold that of Ral, whereas levormeloxifene elevated MMP2 activity to a level 12-fold that of Ral. These data show that one of the significant differences between E and Ral signaling in the uterus is the regulation of genes and proteins associated with matrix integrity. This may be a potential key difference between the action of SERMs in the uterus of postmenopausal women.

Animals↗