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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 19 recordsLinked to original sources

Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis.

Intrarenally synthesized angiotensin II (Ang II) may be involved in the progression of glomerulonephritis, leading to irreversible glomerulosclerosis. There is increasing evidence that systemic angiotensin receptor blocker (ARB) treatment has beneficial effect on the prognosis of progressive glomerulonephritis and diabetic nephropathy. However, the cellular and molecular mechanisms behind this therapeutic effect of ARB remain unclear. In this study, we used a novel strategy of local ARB delivery via type-1 collagen sponge, to treat progressive glomerulonephritis that would result in irreversible glomerulosclerosis in our previously established rat model. At days 9 and 14 after disease induction, mild proteinuria, 20.7+/-4.7 and 10+/-1.3 mg/day, was found. Local ARB treatment reduced proteinuria significantly to 3.19+/-3.2 and 5.25+/-0.95 mg/day (P < 0.01), respectively. Scoring of glomerular matrix expansion and sclerotic index revealed that local ARB treatment significantly ameliorated glomerular pathology. Ang II type 1 receptor mRNA expression was remarkably enhanced in the Ang II group and ARB treatment reversed this effect at 14 days. Local delivery of ARB significantly improved glomerular blood flow levels, compared to the untreated disease control group, from 710+/-18.25 to 859.44+/-22.86 microm/s, respectively. Local delivery of ARB into the kidney affected local RAS and thus improved the renal injury and function in the potentially progressive glomerulosclerosis of rat model.

Angiotensin II↗

Ratio of low serum zinc levels in elderly Japanese people living in the central part of Japan.

OBJECTIVE: Elderly patients often have impaired taste, nausea, anorexia and delayed healing of decubitus. In many of these patients, serum zinc levels are low and they respond to zinc supplementation. To date, no epidemics of zinc deficiency have been reported in Japan. We studied the prevalence of zinc deficiency and its causative factors in a typical local town in Japan. DESIGN: Cross-sectional study. SETTING: Nagano Prefecture (central Japan). SUBJECTS AND METHODS: Serum zinc levels were measured in 1009 habitants (18-96 years old) who participated in an annual mass health examination program of the City in 2003. Of all subjects, 86 with low serum zinc (<65 microg/dl) or high zinc (> or =90 microg/dl) levels were randomly selected, and a dietary survey using 24-h recalling methods for 2 consecutive days was performed in 2004. Among them, blood was collected in the morning from 50 subjects (26-94 years old). RESULTS: The percentage of those with low serum zinc levels (2.5th percentile of Americans) was 37.9% in the elderly (> or =60 years old). The age-adjusted prevalence of low serum zinc was 21.1% in the aged population. A positive correlation was detected between zinc intake and serum zinc levels in elderly subjects (> or =60 years old). CONCLUSIONS: The possibility of zinc deficiency in adult inhabitants in central Japan rises with age. The deficiency correlates with dietary zinc intake.

Adolescent↗

Exclusive measurement of the nonmesonic weak decay of the lambda(5)He hypernucleus.

We performed a coincidence measurement of two nucleons emitted from the nonmesonic weak decay of lambda(5)He formed via the 6Li(pi+, K+) reaction. The energies of the two nucleons and the pair number distributions in the opening angle between them were measured. In both np and nn pairs, we observed a clean back-to-back correlation coming from the two-body weak reactions of lambda p --> np and lambda n --> nn, respectively. The ratio of the nucleon pair numbers was N(nn)/N(np) = 0.45 +/- 0.11(stat) +/- 0.03(syst) in the kinematic region of cos theta(NN) < -0.8. Since each decay mode was exclusively detected, the measured ratio should be close to the ratio of gamma(lambda p --> np)/gamma(lambda n --> nn). The ratio is consistent with recent theoretical calculations based on the heavy meson and/or direct-quark exchange picture.

Journal Article↗

Turbulence of glomerular hemodynamics involved in progressive glomerulosclerosis.

There is increasing evidence that changes of glomerular hemodynamics or glomerular growth responses may promote the development of glomerulosclerosis. Major problems retarding research progress include lack of suitable experimental animal models, with the exception of the ablation model, and the need for in vivo real-time analysis of glomerular hemodynamics. This study examined the sequence of pathological changes from the viewpoints of microcirculation and histopathology, from the acute stage to the chronic course and the final stage of glomerulosclerosis, using the confocal laser scanning microscope system. There is a marked difference in prognosis between sham-operated (two-kidney) and nephrectomized (one-kidney) rats after injection with anti-Thy-1 antibody. The former reversibly returns to normal and the latter irreversibly go to progressive sclerosis, respectively. The turning point determining the progression of glomerulosclerosis in both groups seemed to be the period from 7 to 14 days after disease induction, when disturbance of local intraglomerular blood flow continued in the one-kidney groups. In conclusion, this study provides the first hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulosclerosis.

Albumins↗

Pioglitazone increases circulating adiponectin levels and subsequently reduces TNF-alpha levels in Type 2 diabetic patients: a randomized study.

BACKGROUND: Adipocytokines are involved in the development of insulin resistance and endothelial dysfunction in diabetic patients. However, the relationship between these factors remains unclear. We observed a chronological change in circulating adipocytokines and blood pressure levels with administration of oral hypoglycaemic agents in Type 2 diabetic (T2DM) subjects. METHODS: Thirty poorly controlled T2DM subjects (aged 60.1 +/- 1.5 years, 11 males and 19 females) were randomized into two groups: voglibose (initial dose 0.6 mg/day, increased to 0.9 mg/day) and pioglitazone (initial dose 15 mg/day, increased to 30 mg/day). RESULTS: Both treatment groups showed a similar improvement in glycaemic control. In pioglitazone-treated patients, circulating adiponectin levels were significantly increased from 4 weeks after the start of treatment, and until the end of the study at 12 weeks. Plasma tumour necrosis factor-alpha (TNF-alpha) levels were significantly decreased only at 12 weeks. In contrast, no significant changes in plasma adiponectin or TNF-alpha levels were observed in voglibose-treated patients. Plasma PAI-1 and leptin levels were not significantly changed at 12 weeks in either treatment group. Pioglitazone significantly decreased systolic and diastolic blood pressure levels at 12 weeks, but voglibose had no effect. CONCLUSION: In summary, pioglitazone caused an immediate increase in circulating adiponectin levels, followed by a reduction of TNF-alpha. The observed increase in circulating adiponectin could be related to decreases in both systolic and diastolic blood pressure.

Adiponectin↗

A survey of the appropriate use of antiseptic agents in the operating room of several key health care facilities. A comparison between surveys in 2000 and 2004.

Since 2000, new hand and environmental hygiene guidelines have been published by the Center for Disease Control and Prevention (CDC) based on scientific evidence. Accordingly, we expected that the use of disinfectants in clinical settings had been changed. To compare the use and amount of disinfectants before and after the publication of these guidelines, we conducted a questionnaire-based survey on the use of antiseptic agents in operating rooms (ORs) in 6 key hospitals over a period of a month in 2000 and 2004. As a result, the amount of disinfectants used in ORs was reduced in all hospitals in 2004. Especially, amphoteric detergents and glutaral products showed significant reductions in the total amount used in the 6 hospitals, by 94.8 and 96.8%, respectively. The use of povidone-iodine (PVP-I) was decreased by 23.4% overall, although it was increased in 3 hospitals by 11.0-58.6%. The number of applications of PVP-I on the surgical site did not change; however, the site was left to dry without wiping after PVP-I application more frequently in 2004 than in 2000. The time for surgical scrubbing was shortened in 2004, but brush scrubbing was still used as often as in 2000. Many of the hospitals used brush scrubbing in conjunction with alcohol-based rubs. These results indicated changes in infection control measures in hospital settings after publication of the new CDC guidelines; environmental disinfection had been limited and excessive use of disinfectants reevaluated.

Anti-Infective Agents, Local↗

[Left atrial myxoma combined with coronary artery bypass grafting].

We experienced 2 cases of surgical treatment for left atrial myxoma combined with coronary artery bypass grafting (CABG) using only in situ arterial grafts. A 58-year-old man who had undergone CABG [left internal thoracic artery (LITA)-right coronary artery (RCA) and saphenous vein graft (SVG)-left anterior descending artery (LAD)] 14 years before was admitted to our hospital, complaining of anterior chest pain. Coronary arteriography demonstrated total occlusion of the LAD and RCA, as well as the stenosis of high lateral branch (HL) and SVG. Left atrial myxoma was incidentally detected by echocardiography. Myxoma was resected at first, and then the right internal thoracic artery (RITA) was anastomosed to the LAD. The postoperative course was uneventful. A 69-year-old woman was admitted to another hospital, complaining of chest pain and dyspnea. Coronary arteriography revealed stenosis of LAD, left circumflex artery (LCx) and HL, as well as left main trunk (LMT). Left atrial myxoma was incidentally detected by echocardiography. Myxoma was resected at first, and then CABG [LITA-HL, gastroepiploic artery (GEA)-RCA and RITA-LAD] was carried out. The postoperative course was uneventful. The priority between CABG and the surgical treatment for cardiac myxoma remains controversial from the point of view of myocardial protection and prevention of systemic embolism of myxomal fragment.

Aged↗

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats.

AIMS/HYPOTHESIS: Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats. METHODS: STZ-induced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks. To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-kappaB) activity. RESULTS: Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-beta1), type IV collagen protein production and NF-kappaB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment. CONCLUSIONS/INTERPRETATION: Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-kappaB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.

Albuminuria↗

Inhibition of appetite by nasal leptin administration in rats.

OBJECTIVE: Leptin inhibits appetite and reduces body weight. However, subcutaneous leptin administration is not very effective on weight reduction. The present studies were undertaken to test the hypotheses that nasally administered leptin effectively accesses to the brain and inhibits appetite. METHODS: Recombinant leptin (0.5 mg/rat) was administered into the bilateral nasal spaces of rats (i.n.). Changes in serum immunoreactive leptin (IRL) and cerebrospinal fluid (CSF)-IRL concentrations after i.n. leptin administration were compared after intraperitoneal (i.p.) administration. The influence of 0.1 or 0.5% lysophosphatidylcholine (LPC) as an optimizer of leptin absorption was examined. The anorexic effects of i.n. leptin were compared with i.p. leptin in ad libitum fed rats. RESULTS: The i.n. leptin increased CSF-IRL concentrations, although serum IRL concentrations of rats administered leptin i.n. were lower than those administered i.p. The addition of 0.1 and 0.5% LPC dose-dependently increased serum IRL concentrations, but did not modify CSF-IRL concentrations in i.n. leptin-treated rats. The i.n. leptin inhibited dark-time food consumption at 0-1 h and 3-6 h in ad libitum fed rats. In contrast, i.p. leptin reduced food consumption only for an hour. Phosphorylated signal transducer and activator of transcription (STAT) 3 immunoreactive cells increased in the arcuate nucleus (ARC) of the hypothalamus at 3 h only following i.n. leptin. CONCLUSION: The present study demonstrated that i.n. leptin caused longer inhibition of appetite and phosphorylation of STAT3 in ARC. It is concluded that the trans-nasal route may be useful for the selective access of leptin to the brain in obese people.

Administration, Inhalation↗

Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury.

Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin-6 (IL-6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) in the treatment of acute SCI in mice. Immediately after contusive SCI with a modified NYU impactor, mice were intraperitoneally injected with a single dose of MR16-1 (100 microg/g body weight), the lesions were assessed histologically, and the functional recovery was evaluated. MR16-1 not only suppressed the astrocytic diffentiation-promoting effect of IL-6 signaling in vitro but inhibited the development of astrogliosis after SCI in vivo. MR16-1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16-1 compared with control mice. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI.

Analysis of Variance↗

[Thoracoscopic pericardial resections for malignant pericardial effusions].

We have performed 5 thoracoscopic pericardial resections for malignant pericardial effusions. An initial trocar was placed in the seventh or eighth intercostal space posterior to the midaxillary line. Two additional trocars were placed, usually in the sixth intercostals spaces in the anterior axillary and posterior axillary lines. Using an endoscopic grasping instrument and scissors through the working ports, a pericardial resection was performed. All patients were successfully managed by thoracoscopic pericardial resections. Two of the 5 patients had associated malignant pleural effusions that were able to be managed at the same time by thoracoscopy. The average chest tube duration was 1.8 days. There has been no reaccumulation of pericardial effusions in all patients at an average follow-up of 5 months. The thoracoscopic approach could be minimally invasive and the procedure of choice in performing pericardial resections in selected patients with malignant pericardial effusions who are expected to have a reasonable life expectancy.

Adenocarcinoma↗

Contrasting patterns of genetic variation in the two sympatric geckos Gekko tawaensis and G. japonicus (Reptilia: Squamata) from western Japan, as revealed by allozyme analyses.

Allozyme variation in two congeneric sympatric geckos, Gekko tawaensis and G. japonicus, from western Japan was examined. These species show similar densities and spatial arrangements of populations in this region, and their genetic structures are thus expected to have been formed under the influences of comparable geohistorical, environmental, and demographic factors. Results of the analyses, however, revealed strikingly different genetic patterns in the two species. Populations of G. tawaensis invariably showed a remarkably lowered heterozygosity (0-0.017) compared to G. japonicus (0.089-0.124). On the other hand, the genetic heterogeneity among populations is much greater in G. tawaensis (F(ST)=0.726) than in G. japonicus (F(ST)=0.101). The Mantel test failed to detect any significant correlations between log (estimated migration rate) and log (geographic distance) in either species, or between matrices of interpopulation pairwise F(ST) for the two species. These results suggest that, in each species, formation of the current genetic structure in western Japan has been chiefly influenced by stochastic factors, rather than the geohistorical architecture of this region. The high F(ST) and low heterozygosity in G. tawaensis suggest the effects of severe local fragmentation. On the other hand, the relatively low F(ST) and high heterozygosity in G. japonicus imply extensive gene flow among populations. Absence of significant correlations between the estimated migration rate and geographic distance in G. japonicus may suggest that such gene flow is promoted by human-mediated transport of this primarily house-dwelling lizard.

Animals↗

[Thoracoscopic surgery for metastatic lung tumors: computed tomography-guided localization with use of a needle with a suture].

When a metastatic lung tumor is found to be deep to the visceral surface of the pleura, or when it is found to be a small lesion, it may important to help identify the lesion by preoperative methods in order to localize it at the time of thoracoscopic operation. We performed computed tomography-guided localization of metastatic lung tumors with use of a needle with a suture in 11 cases prior to thoracoscopic resection. Placement of the needle, immediately before moving to the operation room were successfully performed in all patients. It took from 16 to 25 minutes (20.3 minutes on average). Complications included minimal pneumothorax in 8 patients, mild airway bleeding in 2, and penetration through the middle lobe to the lower lobe of the right lung in 1. However, treatment was not necessary in any of the patients. Thoracoscopic resections were successfully achieved in all patients. Our technique may be a simpler technique and advantageous for identification of small lesions and lesions deep to the visceral surface of the pleura during the thoracoscopic operation for metastatic lung tumors.

Aged↗

[A thoracoscopic technique with fibrin glue and polyglycolic acid mesh for the injured lung during thoracoscopic operation].

The injury of the lung occurred during thoracoscopic operation, especially, of the fragile, severely emphysematous lung is often difficult to treat. A fibrin glue spraying device in which an air compressor was connected to an intravenous catheter was constructed, and connected to a Dupuloject syringe. Fibrin glue was administered by spraying on the target lesion under a thoracoscopic vision. The procedure was done while the tip of the intravenous catheter was held and manipulated with forceps through a thoracoport. And then, the polyglycolic acid (PGA) mesh that had been cut into small pieces was put on the target lesion with forceps. Fibrin glue was sprayed on the lesion again in the above-mentioned manner. When necessary, the procedure was repeated. Our technique during thoracoscopic operation may be easy to manipulate and be able to apply the target lesion uniformly within a short time with a successful repair.

Aged↗

Long-term response to zonisamide in patients with West syndrome.

The long-term effectiveness of zonisamide (ZNS) was evaluated in 11 patients with West syndrome (7 symptomatic) who had cessation of spasms with ZNS monotherapy. During the follow-up period (24 to 79 months, mean = 53 months), this response was maintained in 7 patients (3 symptomatic, relapse rate = 36%), including 2 children in whom ZNS was successfully discontinued. No serious adverse reactions were noted. ZNS may be both effective and well tolerated for the treatment of West syndrome.

Adolescent↗

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer.

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.

Aged↗