Synergism between creep ductility and grain boundary bubbles

The marked decrease in creep ductility that can be caused by internal pressure in grain boundary pores is modelled to treat the interaction between boundary diffusion, power law creep, and bubble pressure. The application to 2.25 Cr−1 Mo steel in high pressure hydrogen is treated numerically using a computer program since here the internal methane pressure in pores is known, and kinetic data exists. Reasonable agreement is obtained between the predictions and the observed loss in ductility in the presence of 21 MPa of hydrogen. With methane pressurized bubbles, the model suggests intergranular fracture is powerlaw creep limited at essentially all temperatures and stresses. Thus one predicts the hydrogen attack resistance in service to be strongly influenced by the creep strength of the alloy. In the absence of hydrogen (methane), intergranular fracture should be limited by diffusion creep and thus much more sensitive to pore density and boundary diffusion rate than strength. Possible application to recent high temperature steamline failures in welded pipe and to helium effects in nuclear reactor materials are also indicated.     

Effect of low-dose methylprednisolone on calcium balance and bone composition in rats

A rare case of Gorham's disease affecting the radius in a 46-year-old woman is presented. It was studied by plain radiography, MRI, and scintigraphy, including three-phase radionuclide bone scan and thallium scan. Three-phase bone scan demonstrated slightly decreased activity in the affected portion of the forearm in the early phase, but showed increased activity on the blood pool and delayed imaging. A thallium scan revealed no abnormalities. Histopathologic examination revealed osteoclastic activity and scar tissue with minimal remaining vasculature.     

膨胀剂修饰的阴阳黏土在橡胶中的协效作用

分别采用对硝基苯甲酸和三聚氰胺磷酸盐作为膨胀阻燃剂组分有机修饰阴阳离子黏土:层状双氢氧化物和蒙脱土.将有机修饰的层状双氢氧化物(OLDH)和有机修饰的蒙脱土(OMMT)与超微氢氧化镁(HFMH)一起作为无卤阻燃剂,通过熔融插层法,加入到丁腈橡胶(NBR)中,制备无卤阻燃NBR,/OLDH/OMMT/HFMH纳米复合材料.采用傅里叶红外光谱、X射线衍射、透射电镜、热重分析、氧指数、垂直燃烧和力学测试研究NBR/OLDH/OMMT/HFMH纳米复合材料的形态结构、协效作用、热和力学性质.结果表明能够得到剥离或插层的纳米复合材料,且OLDH和OMMT均匀分散在NBR基体中.归于膨胀阻燃剂组分有机修饰的OLDH和OMMT的协效作用,含有5份OLDH和5份OMMT的NBR-3在700℃有最高的残碳量.NBR-3样品主链的热稳定性比NBR-5样品(含有10份OMMT)和NBR-1样品(含有10份OLDH)的高15～18℃.在所有的样品中,NBR-3样品的氧指数最高,为38%.样品NBR-2、NBR-3、NBR-4均能通过V-0级.力学性能表明有机修饰的纳米片层能够明显地提高样品的拉伸强度和100%伸长时应力.     

Effects of glibenclamide and nicorandil in post-ischaemic contractile dysfunction of perfused hearts in normotensive and spontaneously hypertensive rats

OBJECTIVE: We have demonstrated previously that nicorandil, an ATP-sensitive potassium channel opener, improved post-ischaemic contractile dysfunction of perfused hearts in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats dose-dependently. This study aimed to characterize the effect of glibenclamide, an ATP-sensitive potassium channel blocker, and nicorandil in post-ischaemic contractile dysfunction of SHR and WKY rats. METHODS: The perfused hearts were subjected to 30 min of global ischaemia and then 30 min of reperfusion. Administration of 10 or 50 mumol/l glibenclamide or of a combination of glibenclamide and 300 mumol/l nicorandil was performed for 10 min before the ischaemia. The left ventricular developed pressure and end-diastolic pressure were measured. RESULTS: Postischaemic contractile function was better in WKY rats than it was in SHR. Neither glibenclamide nor a combination of glibenclamide and nicorandil influenced the postischaemic contractile function or increased the incidence of reperfusion arrhythmias. The recoveries of coronary flow and heart rate after reperfusion were poor and the incidence of reperfusion arrhythmias was low in SHR. CONCLUSIONS: These results suggest that nicorandil improves postischaemic contractile dysfunction via a mechanism involving ATP-sensitive potassium channel opening both in SHR and in WKY rats. The hypertensive hearts were more susceptible to cardiac reperfusion dysfunction, compared with normal hearts.     

Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers and terminals. Growth hormone-releasing hormone-, somatostatin-, alpha-melanocyte stimulating hormone-, adrenocorticotropin-, beta-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers.     

Myocardial distribution and biotransformation in vitro and in vivo of nicorandil in rats, with special reference to mitochondria

This study reports subcellular localization of nicorandil in the myocardium and metabolism in mitochondria after oral dosing of 3 mg/kg nicorandil to rats. In the in vitro experiments, nicorandil, which was incubated with tissue homogenates (liver, kidney, heart, and small intestine), was metabolized to its denitrated compound, SG-86, and unknown substances. In the absence of a NADPH-generating system in the heart, the metabolic activity existed only in the mitochondrial fraction, but not in cytosolic and microsomal fractions. In the presence of the system, the activity in the mitochondrial fraction became much higher. To examine subcellular distribution of nicorandil in the myocardium, [14C]nicorandil was orally given to rats. Fifteen minutes after oral dosing of 3 mg/kg [14C]nicorandil, of which myocardial concentration reached a peak, nicorandil and SG-86 were found in mitochondrial fractions as well as in cytosolic and microsomal ones of the heart. Electron-microscopic autoradiograms, 15 min after oral dosing of 3 mg/kg [3H]nicorandil to rats, also showed the existence of the silver grains (showing radioactivity) in mitochondria of the heart. We conclude that nicorandil given orally is distributed in mitochondria of the heart, being partly transformed into SG-86, and that the myocardial mitochondria may be a potential site of action of nicorandil, an opener of KATP channels, which have been demonstrated to be present in this subcellular particle.     

Synergism between NMDA and domoic acid in a murine model of behavioural neurotoxicity

We have examined the behavioural neurotoxicity of domoic acid (DOM) and kainic acid (KA) in mice following administration of ligands active at the N-methyl-d-aspartate (NMDA) receptor. Groups of female CD-1 mice (n=4) were injected i.p. with saline or one of three doses of either DOM or KA. Doses of DOM and KA were selected from the steep portion of the respective dose response curves and were equitoxic when compared between the two ligands. Toxicity was recorded as both total cumulative toxicity over 60 min according to a previously validated 7 point rating scale, and as the latency to the onset of tremors and/or convulsions. Five minutes prior to administration of either agonist mice were injected with either saline, NMDA (40 mg/kg) or a combination of NMDA and 15 mg/kg CPP (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid). Neither NMDA nor CPP at these doses produced significant changes from baseline responding when injected prior to saline. Injection of NMDA prior to DOM, however, resulted in significantly increased cumulative toxicity and significantly reduced latencies to seizures at the two highest doses of DOM (3.75 and 5.0 mg/kg). NMDA-induced potentiation of DOM toxicity was completely antagonized by co-administration of CPP. In contrast, injection of NMDA prior to KA did not result in significant changes in KA toxicity at any of the doses tested using either index of behavioural toxicity. These results confirm previous reports of synergism between DOM and ligands acting at the NMDA receptor in isolated neurons, and provide further evidence of pharmacological dissociation of the actions of DOM and KA in vivo.     

Synergism between N-acetylcysteine and doxorubicin in the prevention of tumorigenicity and metastasis in murine models

The thiol N-acetylcysteine (NAC) is a promising cancer chemopreventive agent which acts through a variety of mechanisms, including its nucleophilic and antioxidant properties. We have recently shown that NAC inhibits type-IV collagenase activity as well as invasion, tumor take and metastasis of malignant cells in mice. NAC is also known to attenuate the cardiotoxicity of the cytostatic drug doxorubicin (DOX, Adriamycin). The present study was designed to evaluate whether the combination of NAC and DOX treatments in mice injected with cancer cells could affect their tumorigenic and metastatic properties. Six separate experiments were carried out, using a total of 291 adult female mice. In experimental metastasis assays, in which B16-F10 melanoma cells were injected i.v. into (CD-1)BR nude mice, DOX significantly reduced the number of lung metastases when administered i.v. at a dose of 10 mg/kg body weight, 3 days after the i.v. injection of cancer cells. NAC inhibited lung metastases when added to the medium of cancer cells before their i.v. injection. The combined treatment with DOX and NAC, under various experimental conditions, was highly effective, showing a synergistic reduction in the number of mestastases. In tumorigenicity and spontaneous metastasis assays, in which B16-BL6 melanoma cells were injected s.c. into the footpad of C57BL/6 mice, DOX decreased the number of lung metastases when given i.p. at 2 mg/kg body weight. Oral NAC exerted significant protective effects, and considerably prolonged survival of mice. The combined treatment with DOX and NAC again showed synergistic effects on the frequency and weight of primary tumors and local recurrences, and completely prevented the formation of lung metastases in the experiment in which these end-points were evaluated at fixed times. While injection of DOX 7 days after implantation of cancer cells failed to improve the cancer-protective effects of NAC, its injection after I day resulted in a striking inhibition of lung metastases. These findings demonstrate an evident synergism between DOX (given parenterally) and NAC (given with drinking water) in preventing tumorigenicity and metastases. The indications of these animal studies warrant further evaluation in clinical trials.     

Interrelationship of cardiovascular effects, plasma levels of nicorandil, and vascular cGMP formation in conscious rats

OBJECTIVE: To determine the reproducibility of duplex Doppler waveform analysis and fetal cardiac interventricular septal thickness measurement and to compare these parameters in matched pregnancies with and without well-controlled maternal Type 1 diabetes at 18-20 weeks of gestation. DESIGN: A prospective blind twin cohort study and a blinded inter-observer and intra-observer agreement study. SETTING: A tertiary referral prenatal diagnostic unit within a university hospital. RESULTS: Good inter- and intra-observer agreement was found for the measurement of transvalvular peak flow velocities and the duration of ventricular ejection in the fetal heart. Inter-observer agreement for aortic flow acceleration rate was poor. M-mode measurement of interventricular septal thickness showed moderate reproducibility. The mean (SD) width of the interventricular septum in the fetuses of well controlled diabetic women was 2 1 mm (0.2 mm), and was significantly greater (P=0.01) when compared with the corresponding value in matched controls [1.9 mm (0.2 mm)]. No cardiac functional differences were evident. CONCLUSIONS: On-screen video analysis of Doppler cardiac flow waveforms and M-mode measurement of intraventricular septal thickness demonstrated good reproducibility. The fetuses of well controlled diabetic pregnancies demonstrated signs of altered cardiac morphology early in pregnancy, before any evident alterations in cardiac function.     

Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA

We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance. Serum arachidonic acid (AA) level was decreased by the administration of low-dose EPA and tended to be decreased by the administration of low-dose DHA, whereas tumour AA levels were not changed. The administration of low-dose EPA and DHA may be useful for inhibiting the incidence of breast cancer.     

Synergism in biofilm formation between Salmonella enteritidis and a nitrogen-fixing strain of Klebsiella pneumoniae

A laboratory reactor, which simulates biofilm formation in water pipes, was used to study interactions in biofilm formation between a nitrogen-fixing strain of Klebsiella pneumoniae and Salmonella enteritidis. The level of attachment of Salm. enteritidis was higher in the binar biofilm than in the single species biofilm. In the initial colonization phase the binary biofilm contained a much higher proportion of metabolically active cells than in single species biofilms formed by either Salm. enteritidis or Kl. pneumoniae. When a pulse of Salm. enteritidis was passed over an already established biofilm of Kl. pneumoniae it rapidly became integrated into the biofilm, from where it was subsequently released into the water column, along with Kl. pneumoniae. Klebsiella pneumoniae fixed nitrogen in the presence of Salm. enteritidis in both types of biofilm.     

Concurrent analysis of neuropeptides and biogenic amines in brain tissue of rats treated with electroconvulsive stimuli

Human serum biotinidase, purified to homogeneity (1920 units/mg protein), was incubated with biocytin prior to electrophoresis and transblotting with avidin-peroxidase. Avidin reacted with biotinidase maximally when incubated at pH 7.5-9, less at pH 7 and none below pH 7. No avidin reactivity occurred when biotinidase was incubated with biotin or in the absence of biocytin. Inclusion of the nucleophilic acceptors, ethanolamine or hydroxylamine, to the incubation mixture with biocytin and biotinidase resulted in loss of avidin reactivity. High concentrations of mercaptoethanol also prevented avidin reactivity. These results suggest that biotinidase can be biotinylated in the presence of biocytin at neutral to alkaline pH probably through a thioester bond formed with a cysteine residue in the active site of the enzyme. Biotinidase may then function as a biotinylating enzyme when incubated with appropriate nucleophilic acceptors.     

Abnormalities of neuropeptides and neural markers in the esophagus of fetal rats with adriamycin-induced esophageal atresia

BACKGROUND/PURPOSE: To investigate the distribution of neural markers and neuropeptides in esophageal atresia (EA). METHODS: A fetal rat model with Adriamycin-induced EA was used. The animals were divided into four groups: (1) control group, (2) saline-injected group, (3) Adriamycin administered but without the development of EA, and (4) Adriamycin-induced EA group. Specimens of the distal esophagus from each group were immunostained using antibodies to S100, protein gene product 9.5 (PGP), somatostatin, vasoactive intestine peptide (VIP), bombesin, galanin, substance P, neuropeptide Y (NPY), calcitonin gene-related product (CGRP), met-encephalin, nitric oxide synthase, and tyrosine hydroxylase. RESULTS: The total cross-sectional area of the distal atretic esophagus was significantly smaller than controls (P = .01), the submucosa being the component most affected (0.0465 v 0.0234 mm). Immunoreactivity for S100 and galanin were significantly elevated in the atresia group (0.0288 v 0.0079 and .001 v 0.000). In addition, there was also an increase in CGRP and Substance P in the atretic group. CONCLUSION: The elevated levels of S100 and galanin could explain the disordered motility observed in patients who had esophageal atresia.     

Evaluation of organic solvent-induced inflammation modulated by neuropeptides in the abdominal skin of hairless rats

Implementing a program as complex as continuous venovenous hemodialysis without the involvement of nephrology nurses is a challenge. However, with proper planning, appropriate staff support, and the ability to make changes as implementation proceeds, a successful program can be developed. Our reward is that we are now able to offer a therapy that is important and potentially lifesaving to those critically ill patients with renal failure who are unable to tolerate intermittent hemodialysis.     

Investigation of oxidant stress and vasodepression to glyceryl trinitrate in the obese Zucker rat in vivo

OBJECTIVE: To describe risk factors and explore mechanisms of ischemic strokes after general surgery. BACKGROUND: Strokes follow general surgery in about 0.08% to 2.9% of cases. Patients with previous cerebrovascular disease, atrial fibrillation, hypertension, advanced age, or atherosclerosis were found to have an increased risk. Knowledge of factors involved may guide physicians in determining the overall risk of surgery. METHODS: This case-control study was performed in a referral center. A total of 61 patients identified through a computerized database with ischemic strokes after surgical procedures-excluding heart, brain, vessels, or neck-between July 1986 and July 1996 were studied. Procedures included 11 urogenital, 16 gastrointestinal, 17 orthopedic, 12 pulmonary, and 5 other. A total of 122 randomly selected controls were matched for age, sex, procedure, and year of procedure. Main outcome measures included arterial territory, timing, risk factors, and perioperative events. Differences were expressed as adjusted odds ratios (AOR) with 95% confidence limits (CL), using multivariate conditional logistic analyses for matched case-control design. RESULTS: Arterial territory included 37 middle cerebral artery, 11 posterior circulation, 7 borderzone, and 6 multiple. Median procedure to stroke interval was 2 days (range, 0 to 16); 10 patients had intraoperative strokes. Three major risk factors emerged: previous cerebrovascular disease (AOR 12.57, 95% CL 2.14/73.70), chronic obstructive pulmonary disease (COPD) (7.51, 1.87/30.12), and peripheral vascular disease (PVD) (5.35, 1.25/22.94). After adding stroke-related factors, PVD (14.70, 2.01/107.71) and COPD (10.04, 1.90/53.14) remained the strongest variables; blood pressure (1.05, 1.01/1.10) and urea (1.04, 1.01/1.07) contributed slightly. Hypotension did not contribute. Four patients (6.6%) and no controls had diffuse intravascular coagulation (p = 0.01). Four stroke patients had myocardial infarction (6.6% versus 0%; p = 0.01). CONCLUSIONS: Ischemic strokes after general surgery most commonly occur after an asymptomatic interval. Previous cerebrovascular disease, COPD, and PVD greatly increase the risk. Hypotension rarely accounts for postoperative strokes. Major comorbidity of the patient at risk seems more important than complicating events during surgery.     

Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion: role of selectins

BACKGROUND: Neutrophils (PMNs) are known to contribute to both cardiac dysfunction and myocardial necrosis after reperfusion of an ischemic heart. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts after ischemia and reperfusion. METHODS AND RESULTS: Control rat hearts not subjected to ischemia were perfused without blood cells for 80 minutes. Additional control rat hearts were perfused with 75x106 PMNs, with 100x106 platelets, or with 75x106 PMNs+100x106 platelets over a 5-minute perfusion followed by a 75-minute observation period. No significant reduction in coronary flow, left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dtmax) was observed at the end of the observation period in any nonischemic group. Similarly, global ischemia (I) for 20 minutes followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of 10% to 12% (P<0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50% to 60% in all measurements of cardiac function (P<0.001). These dual-cell-perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity, indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiodynamic effects as well as MPO accumulation and PMN infiltration were markedly attenuated by a sialyl LewisX-oligosaccharide or a recombinant soluble P-selectin ligand, which inhibits selectin-mediated cell adhesion. CONCLUSIONS: These results provide evidence that platelets and neutrophils act synergistically in provoking postreperfusion cardiac dysfunction and that this may be largely due to cell-to-cell interactions mediated by P-selectin. These findings may help explain the reperfusion injury phenomenon.     

The effects of nicorandil on electrophysiological changes in acute myocardial ischemia and reperfusion

This study was undertaken to clarify the effects of nicorandil on electrophysiological changes during acute ischemia and following reperfusion. We prepared an acute ischemic heart model by ligating the left anterior descending coronary artery in 27 dogs. After 10 minutes, reperfusion was performed. The changes in ventricular effective refractory period (ERP) and intramyocardial conduction time (ICT) were compared between the nicorandil group (n = 12) which received nicorandil intravenously before the coronary ligation and the control group (n = 15). In the control group, the ERP was shortened during ischemia, and rapidly shortened immediately after reperfusion, but was slightly prolonged 10 minutes after reperfusion. The ICT was prolonged during ischemia, but returned to the pre-ischemia value after reperfusion. In the nicorandil group, the changes in ERP and ICT were significantly inhibited compared to those in the control group. The incidence of ventricular fibrillation (VF) during reperfusion was 42% in the control group. However, there was no VF during reperfusion in the nicorandil group. Therefore, nicorandil may correct both the delayed conduction and the uneven ventricular effective refractory period detected during acute ischemia and following reperfusion, inhibiting the development of ventricular arrhythmia during reperfusion.     

Corrosion Inhibition Synergism between Lanthanum （ Ⅲ ） Ion and 8-Hydroxyquinoline for Zinc in Hydrochloric Acid

The effects of La^3 ion and chelate reagent 8-hydroxyquinoline on the corrosion rate of zinc in hydrochloric acid were investigated by using weight loss method and electrochemical method. It is found that in a specific concentration range of La^3 ion and 8-hydroxyquinoline, the obvious corrosion inhibition synergism is obtained.The mechanism of corrosion inhibition synergism was discussed on basis of adsorption theory.     

Synergism between the effects of dietary cholesterol and coconut oil on plasma, liver and lipoprotein composition of neonatal chick

The nature of the synergism between dietary factors and the development of atherosclerosis has not been fully defined. Our studies showed that simultaneous supplementation of 10% saturated fat rich in 12:0 and 14:0 fatty acids (coconut oil) plus 1% cholesterol to the diet produced a sharp increase of plasma cholesterol, indicating a synergic influence of both dietary constituents. This increase was especially patent in the VLDL fraction, modifying the distribution of other lipid components between the core and the surface of these particles. These changes are consistent with the atherogenic function of VLDL and its responsiveness to dietary manipulation.