Role of inducible nitric oxide synthase on hepatic ischemia and reperfusion injury.
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Animals↗
Biomedical subjects
M Nagayama
Publications and source records attributed to M Nagayama.
Different changes of endothelin-1 after reperfusion in a warm ischemia/reperfusion and transplantation model in pig liver.
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Animals↗
Changes in hepatic microdialysate uric acid levels in porcine liver ischemia/reperfusion.
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Animals↗
Time-lapse viscoelastic imaging of living fibroblasts using force modulation mode in AFM.
Using the force modulation mode in atomic force microscopy, we have succeeded in capturing time-lapse viscoelastic images of living mouse fibroblasts (NIH3T3) for several hours in a physiological condition without damaging the fibroblasts. Elongation of the lamellipodia and swelling of blebs were observed in time-lapse topographic images, which were taken every 10 min. The corresponding viscoelastic responses at a frequency of 600 Hz were visualized as consecutive images. The stiffer part of the cell body was fairly stable and did not show morphological changes for over 1 h. This is probably due to excess condensation of the actin network, hardening the cell cortex, and lowering the cytoskeletal activity. The nuclear portion of the cell body seems to be slightly less viscous than the peripheral region.
3T3 Cells↗
Effects of physical training on the recovery of the autonomic nervous activity during exercise after coronary artery bypass grafting: effects of physical training after CABG.
Analysis of heart rate variability (HRV) can identify patients at risk of sudden cardiac death after myocardial infarction. The present study examined the effect of 2 weeks of supervised aerobic exercise training on the recovery of the autonomic nervous activity, exercise capacity, and cardiac output (CO) after coronary artery bypass grafting (CABG). Twenty-eight patients were randomly divided into the training group or the control group and performed exercise tests at 1 week, 3 weeks, 3 months, 6 months and 1 year after CABG. The HRV was measured, and the high-frequency component of HRV was used as an index of parasympathetic nerve activity (PNA); the plasma norepinephrine concentration (NE) was used as an index of sympathetic nervous activity. Cardiac output was also measured. In the training group, peak VO2, peak CO and PNA during exercise had improved at 3 weeks, but there was no improvement in these indices in the control group. NE decreased 1 week after CABG in both groups. These results indicate that physical training soon after CABG improves not only the exercise capacity, but also PNA.
Aged↗
[Postanoxic-ischemic encephalopathy].
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Brain↗
Magnesium insertion by magnesium chelatase in the biosynthesis of zinc bacteriochlorophyll a in an aerobic acidophilic bacterium Acidiphilium rubrum.
To elucidate the mechanism for formation of zinc-containing bacteriochlorophyll a in the photosynthetic bacterium Acidiphilium rubrum, we isolated homologs of magnesium chelatase subunits (bchI, -D, and -H). A. rubrum bchI and -H were encoded by single genes located on the clusters bchP-orf168-bchI-bchD-orf320-crtI and bchF-N-B-H-L as in Rhodobacter capsulatus, respectively. The deduced sequences of A. rubrum bchI, -D, and -H had overall identities of 59. 8, 40.5, and 50.7% to those from Rba. capsulatus, respectively. When these genes were introduced into bchI, bchD, and bchH mutants of Rba. capsulatus for functional complementation, all mutants were complemented with concomitant synthesis of bacteriochlorophyll a. Analyses of bacteriochlorophyll intermediates showed that A. rubrum cells accumulate magnesium protoporphyrin IX monomethyl ester without detectable accumulation of zinc protoporphyrin IX or its monomethyl ester. These results indicate that a single set of magnesium chelatase homologs in A. rubrum catalyzes the insertion of only Mg(2+) into protoporphyrin IX to yield magnesium protoporphyrin IX monomethyl ester. Consequently, it is most likely that zinc-containing bacteriochlorophyll a is formed by a substitution of Zn(2+) for Mg(2+) at a step in the bacteriochlorophyll biosynthesis after formation of magnesium protoporphyrin IX monomethyl ester.
Acetobacteraceae↗
Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver.
BACKGROUND: Although inhibition of endothelial nitric oxide synthase (eNOS) has been reported to aggravate hepatic ischemia-reperfusion (I/R) injury, the role of inducible nitric oxide synthase (iNOS) has been still unknown. We investigated the role of NO produced by iNOS, and evaluated the effect of an iNOS inhibitor on prolonged warm I/R injury in the pig liver. METHODS: Pigs were subjected to 120 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in serum and hepatic microdialysate NO2- + NO3- (NOx) and the cellular distribution of eNOS and iNOS by immunohistochemistry, including a double-immunofluorescence technique in combination with confocal laser scanning microscopy. The effect of iNOS inhibitor was also investigated. RESULTS: Hepatic I/R induced new nitric oxide production in serum and hepatic microdialysate NOx after reperfusion and severe hepatic damage in the centrilobular region where nitrotyrosine was strongly expressed. Diffuse eNOS expression in sinusoidal endothelium did not differ before and after reperfusion. In contrast, strong iNOS expression in Kupffer cells and neutrophils appeared strongly in the centrilobular region after reperfusion. Pigs with intraportal administration of N(G)-nitro-L-arginine (10 mg/kg) died during the period of ischemia or early in the period of reperfusion with a high mortality rate (80.0%). Intraportal administration of aminoguanidine hemisulfate (10 mg/kg) significantly suppressed nitric oxide production and serum aspartate aminotransferase after reperfusion, inhibited nitrotyrosine expression, and attenuated hepatic damage. CONCLUSIONS: These results indicate that hepatic I/R injury is triggered by centrilobular iNOS expression; and attenuated by inhibition of iNOS.
Animals↗
Effects of neutral sodium hydrogen phosphate on setting reaction and mechanical strength of hydroxyapatite putty.
The setting reaction and mechanical strength in terms of diametral tensile strength (DTS) of hydroxyapatite (HAP) putty made of tetracalcium phosphate, dicalcium phosphate anhydrous, and neutral sodium hydrogen phosphate (Na1.8H1.2PO4) solution containing 8 wt % sodium alginate were evaluated as a function of the Na1.8H1.2PO4 concentration. In one condition, HAP putty was placed in an incubator kept at 37 degrees C and 100% relative humidity. In the other condition, immediately after mixing HAP putty was immersed in serum kept at 37 degrees C. Longer setting times and lower DTS values were observed when HAP putty was immersed in serum regardless of the Na1.8H1.2PO4 concentration. The setting times of the HAP putty in both conditions became shorter with an increase in the Na1. 8H1.2PO4 concentration, reaching approximately 7-13 min when the Na1. 8H1.2PO4 concentration was 0.6 mol/L or higher. The DTS value of HAP putty was relatively constant (10 MPa) regardless of the Na1.8H1. 2PO4 concentration (0.2-1.0 mol/L) when HAP putty was kept in an incubator. In contrast, when HAP putty was immersed in serum, the DTS value was dependent on the Na1.8H1.2PO4 concentration. It increased with the Na1.8H1.2PO4 concentration and reached approximately 5 MPa when the Na1.8H1.2PO4 concentration was 0.6 mol/L, after which it showed a relatively constant DTS value. We therefore would recommend a HAP putty that uses 0.6 mol/L Na1.8H1. 2PO4 since at that concentration the putty's setting time (approximately 10 min) is proper for clinical use and it shows good DTS value (approximately 5 MPa) even when it is immersed in serum immediately after mixing.
Biocompatible Materials↗
The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury.
The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury. In this study, the induction of IRF-1 in response to cerebral ischemia and its role in ischemic brain injury were investigated. IRF-1 gene expression was markedly upregulated within 12 h of occlusion of the middle cerebral artery in C57BL/6 mice. The expression reached a peak 4 d after ischemia (6.0 +/- 1.8-fold; P < 0.001) and was restricted to the ischemic regions of the brain. The volume of ischemic injury was reduced by 23 +/- 3% in IRF-1(+/-) and by 46 +/- 9% in IRF-1(-/-) mice (P < 0.05). The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits. Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke.
Animals↗
Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing.
To evaluate the soft tissue response of calcium phosphate cement (CPC), consisting of an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) under conditions close to those encountered in actual surgical procedures, we implanted three types of CPC [conventional CPC (c-CPC), fast-setting CPC (FSCPC), and antiwashout type FSCPC (aw-FSCPC; formerly called nondecay type FSCPC or nd-FSCPC)] subcutaneously in the abdomens of rats immediately (1 min) after mixing. At 1 week after surgery, histological examination and compositional analysis were performed using light microscopy and powder X-ray diffraction (XRD), respectively. The implanted c-CPC was crumbled completely, whereas FSCPC and aw-FSCPC retained their shape. Large vesicles containing copious inflammatory effusion were subcutaneously formed around the c-CPC. Histologically, many foreign-body giant cells were collected around the c-CPC, and moderate inflammatory cell infiltration was observed at 1 week after surgery. In contrast, the FSCPC and aw-FSCPC were covered with a thin layer of granulation tissue that included few giant cells and presented slight inflammatory cell infiltration, and no effusion was observed. The XRD analysis of the c-CPC revealed the presence of some unreacted DCPA even 1 week after implantation, whereas almost no DCPA was found in the FSCPC or aw-FSCPC. In conclusion, it was found that CPC does not always show excellent tissue response. When c-CPC is implanted subcutaneously in rats immediately after mixing, it fails to set and causes a severe inflammatory response. Therefore, the type of CPC should be chosen according to the clinical particulars. CPC should be used in a manner that assures its setting reaction. We recommend the use of FSCPC and aw-FSCPC for surgical applications, such as orthopedics, plastic and reconstructive surgery, and oral and maxillofacial surgery, where the cement might otherwise crumble due to the pressure before setting.
Animals↗
Effects of an anti-angiogenic agent, TNP-470, on the growth of oral squamous cell carcinomas.
Anti-tumor effects of an anti-angiogenic agent, TNP-470, on the growth of oral squamous cell carcinomas (SCCs) were evaluated in vivo and in vitro. The growth of an oral SCC cell line, HSC-2, inoculated subcutaneously in severe combined immuno-deficiency (SCID) mice was inhibited in a dose-dependent manner by the treatment with this agent. A reduction of microvessels surrounding tumor tissues treated with TNP-470 was observed by immunohistochemistry. Significant side-effects were not observed except for weight loss during the period of treatment with high dose (50 mg/kg) of TNP-470. The direct effects of TNP-470 on oral SCC cell lines were also evaluated in culture. The growth of all eight SCC cell lines tested was inhibited by TNP-470, but the sensitivity of the oral SCC cell lines to TNP-470 was about 1700 times less than that of endothelial cells. These results suggest that TNP-470 inhibits the growth of oral SCC by anti-angiogenic activities and that it may be effective as a new therapy of oral cancer.
Angiogenesis Inhibitors↗
Age-dependent increase in ischemic brain injury in wild-type mice and in mice lacking the inducible nitric oxide synthase gene.
The authors investigated the influence of age on the outcome of cerebral ischemia in wild-type mice and in mice with a deletion of the inducible nitric oxide synthase (iNOS) gene. The middle cerebral artery was permanently occluded in iNOS-null mice and in wild-type (C57BL/6) controls aged 4, 8, 16, and 24 weeks. Infarct volume was determined in thionin-stained brain sections 4 days after permanent middle cerebral artery occlusion. No differences in forebrain volume were found among wild-type and iNOS-null mice at the ages studied (P > 0.05). In C57BL/6 mice (n = 5 to 6/group), neocortical infarct volume corrected for swelling was 28 +/- 5 mm3 in 4-week-old mice, 28 +/- 3 at 8 weeks, 35 +/- 4 at 16 weeks, and 37 +/- 6 at 24 weeks (mean +/- SD). iNOS-null mice (n = 5 to 6/group) had smaller infarcts than wild-type controls at all ages (P < 0.05). However, the magnitude of the reduction was greater in 4-week-old (-29% +/- 10%) or 8-week-old mice (-24% +/- 8%), than in 16-week-old (-14% +/- 10%) or 24-week-old mice (-11% +/- 6%). Neurologic deficit scores improved significantly between 24 and 96 hours in 4- and 8-week-old iNOS-null mice compared with age-matched wild-type mice (P < 0.05). However, in 16- or 24-week-old iNOS-null mice, neurologic deficits did not improve (P > 0.05). The authors conclude that in iNOS-/- and in wild-type mice, the size of the infarct produced by occlusion of the middle cerebral artery is larger in older than in younger mice. However, the reduction in infarct volume observed in iNOS-null mice is age-dependent and is greatest at 1 to 2 months of age. Therefore, age is a critical variable in studies of focal cerebral ischemic damage, both in wild-type mice and in mouse mutants.
Aging↗
The cyclooxygenase-2 inhibitor NS-398 ameliorates ischemic brain injury in wild-type mice but not in mice with deletion of the inducible nitric oxide synthase gene.
The authors investigated the role of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in the mechanisms of focal cerebral ischemia and its interaction with inducible nitric oxide synthase (iNOS). Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) in mice. Infarct volume was measured 96 hours later by computer-assisted planimetry in thionin-stained brain sections. The highly selective COX-2 inhibitor NS398 (20 mg/kg; intraperitoneally), administered twice a day starting 6 hours after MCA occlusion, reduced total infarct volume in C57BL/6 (-23%) and 129/SVeV mice (-21%), and ameliorated the motor deficits produced by MCA occlusion (P < .05). However, NS398 did not influence infarct volume in mice with deletion of the iNOS gene (P > .05). In contrast, the neuronal NOS inhibitor 7-NI (50 mg/kg; intraperitoneally), administered once 5 minutes after MCA occlusion, reduced neocortical infarct volume by 20% in iNOS -/- mice (P < .05). NS398 did not affect arterial pressure, resting CBF or the CBF reactivity to hypercapnia in anesthetized iNOS null mice (P > .05). The data suggest that COX-2 reaction products, in mouse as in rat, contribute to ischemic brain injury. However, the failure of NS398 to reduce infarct volume in iNOS null mice suggests that iNOS-derived NO is required for the deleterious effects of COX-2 to occur. Thus, COX-2 reaction products may be another mechanism by which iNOS-derived NO contributes to ischemic brain injury.
Animals↗
Expression of E-cadherin in oral cancer cell lines and its relationship to invasiveness in SCID mice in vivo.
We examined the expression of E-cadherin in nine oral cancer cell lines. HSC-4, NA, ZA, HOC927 and Ca9-22 cells strongly expressed E-cadherin [E-CD(++) cell line] and HSC-2 and HSC-3 cells weakly expressed E-cadherin [E-CD(+) cell line]. All the cell lines that expressed E-cadherin were of cuboidal morphology and formed cobblestone colonies. In contrast, TSU and HOC313 cells had spindle shapes, formed dispersed colonies, and were completely negative for E-cadherin [E-CD(-) cell line]. Moreover, all cell lines that expressed E-cadherin showed tumorgenicity in SCID mice, but E-CD(-) cell lines did not show tumorgenicity. The tumors derived from E-CD(+) cell lines invaded deeper into the connective tissues than those from E-CD(++) cell lines. In immunohistochemical analysis, the difference was more marked at the edges of the cancer nests. These results suggest that E-cadherin expression was relevant to the cell forms and the differential grade of cultured cells and that reduced E-cadherin in oral cancer may be associated with invasiveness in vivo.
Animals↗
Initiation of ectopic epithelial calcification in a calcifying odontogenic cyst.
Ultrastructural observation was performed on a calcifying odontogenic cyst (COC) associated with an odontoma and arising in the right mandibular region of an 8-year-old Japanese boy. Four types of cells were identified in the epithelial layer of the COC. The basal cells were low columnar in shape and contained some intracellular organelles. They were attached to the neighboring cells with a few desmosomes and resembled inner enamel epithelium of the normal enamel organ. The stellate reticulum-like cells, polygonal in shape, possessed desmosomes and many cytoplasmic projections. Some intracellular organelles and a few bundles of tonofilaments were observed in the cytoplasm. The light oval cells that were pale staining with toluidine blue contained dilated membranous organelles and many relatively evenly distributed tonofilaments. These cells were usually scattered in the vicinity of the focal accumulations of ghost cells, and the cell membrane was discontinuous in parts. The ghost cells contained many bundles of tonofilaments that were 60-240 nm in diameter and arranged in various directions. No intact intracellular organelles were noted in the cytoplasm. They were attached to the neighboring ghost cells with some desmosomes and their cell membrane was discontinuous in parts. A variety of vesicles, 90-450 nm in diameter, were scattered among the tonofilament bundles. Some of these contained needle-like crystals that were considered to be initial calcification sites in ghost cells. These vesicles presented morphological similarities to matrix vesicles, and it is therefore suggested that matrix vesicle-like structures are deeply involved with initiation of calcification of ghost cells in COC.
Calcinosis↗
[Differential epidural block for definitive diagnosis of snapping hip joint].
Snapping hip joint syndrome is defined as snapping phenomenon accompanied by motion of the hip joint. It occurs from various causes, and its diagnosis and treatment are often difficult. We gave anesthesia for surgery against snapping hip joint under patient's active motion for definitive regional diagnosis. Differential epidural block, which precludes pain while maintaining motor function, was performed by 0.25% bupivacaine, 0.5% lidocaine, and additional administration of fentanyl by 25 micrograms. Although the mechanism of differential nerve block remains to be unknown, the case suggests that effective pain block preserving motor function may be achieved by differential epidural block in combination with low concentration of local anesthetics and small dose of opioid.
Adult↗
[Relationship between plasma hormones and ventricular premature contractions in extracorporeal shock wave lithotripsy--significance of human atrial natriuretic peptide (hANP)].
Extracorporeal shock wave lithotripsy (ESWL) is a safe and effective treatment for upper urinary tract stones. However, the mechanism by which this treatment may be involved in causing ventricular premature contractions (VPC) is unknown. We evaluated the relationship between VPC and plasma hormones in patients treated by ESWL. Holter monitoring was performed on 61 outpatients undergoing ESWL with electrocardiographic synchronization for upper urinary tract stones. The levels of cathecolamine, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and human atrial natriuretic peptide (hANP) were measured before, immediately after, and 7 days after ESWL. Systolic blood pressure increased significantly immediately after, and decreased 7 days after ESWL. VPC occurred during 23 treatments (37.7%) but during ESWL no significant relationship was observed with the treatment side or location. Epinephrine increased significantly immediately after ESWL. hANP increased significantly immediately after ESWL, and decreased 7 days later. VPC occurred in all patients who had an hANP value above 40 pg/ml before ESWL. These results suggest that VPC is related to hemodynamic changes, and that hANP can predict VPC during ESWL.
Adult↗