Reduction of infarct size and infiltration of polymorphonuclear leukocytes by a thromboxane synthetase inhibitor. Studies in a rabbit ischemic heart model.

The effect of sodium 6-(2-(1-(1H)-imidazolyl)methyl-4,5-dihydrobenzo(b) thiophene)carboxylate (RS-5186), a potent and long acting thromboxane synthetase inhibitor in vitro and in vivo, on infarct size and on the infiltration of polymorphonuclear leukocytes (PMNs), was studied in a rabbit coronary artery occlusion (1 h)--reperfusion (0.5 h or 3 h) model. The infarcted region was stained with triphenyltetrazolium, and the ratio of infarcted area/left ventricular area was calculated. The infiltration of PMNs into the infarcted region was determined by measuring the PMNs specific enzyme, myeloperoxidase (MPO) activity. In the vehicle treated group, infarct size and MPO activity were increased with increased reperfusion time from 0.5 h to 3 h (infarct size: 15.3 +/- 2.7 to 25.2 +/- 3.2%; MPO activity: 255 +/- 51 to 825.3 +/- 169.4 units/g wet weight). There was also a significant correlation (r = 0.90, p less than 0.01) between the infarct size and MPO activity. In contrast, in the RS-5186 treated group (2 mg/kg i.v.), both infarct size and MPO activity did not increase with prolongation of the reperfusion period (infarct size: 12.8 +/- 5.5 to 10.3 +/- 3.6%; MPO activity: 318.8 +/- 36.7 to 381.2 +/- 72.6 units/g wet weight). In 0.5 h reperfused samples, there was no significant difference in infarct size or in MPO activity between the vehicle treated group and RS-5186 treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained negative inotropism mediated by alpha-adrenoceptors in adult mouse myocardia: developmental conversion from positive response in the neonate.

1. Inotropic responses to alpha-adrenoceptor stimulation and the effects of antagonists were examined in isolated ventricular preparations from neonatal and adult mice. 2. Phenylephrine, in the presence of propranolol, produced positive inotropic responses in neonates up to 1 week after birth, while it produced negative inotropic responses in mice older than 3 weeks. 3. Both positive and negative responses to phenylephrine in neonates and adults, respectively, were antagonized by prazosin, WB4101 (2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane) and 5-methylurapidil, but not by atropine, yohimbine or chlorethylclonidine. 4. Noradrenaline (NA) produced positive inotropic responses both in the neonate and adult; the responses were observed in a lower concentration-range in the neonate than in the adult. WB4101 produced a significant leftward shift of the concentration-response curve for noradrenaline in adult preparations while only a slight rightward shift was observed in the neonate. 5. Our results demonstrate the presence of alpha-adrenoceptor-mediated inotropic responses in the mouse ventricular myocardia. The response to phenylephrine changes from a positive to a negative effect during postnatal development. The responses are mediated by alpha 1-adrenoceptors, and modulate the overall inotropic response to NA in the adult.     

Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.

1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Mouthguards: difference in longitudinal dimensional stability between single- and double-laminated fabrication techniques

Abstract –  Though the use of mouthguards (MGs) has increased with the increase in sporting activities, little is known about the influence of their fabrication methods on longitudinal dimensional stability. The objective of this study was to compare the difference in the longitudinal dimensional stability between single and laminated MGs. Single-layer MGs were made from a 4.0 mm thick ethylene vinyl acetate (EVA) sheet and laminated MGs were made from two 2.0 mm thick sheets of EVA. MGs were kept in a 37°C water bath for 60 h, equivalent to the time period of 3-months inter-oral use. MG deformation was analyzed by measuring designated points on the MG border using a profile projector (J-12, Nikon Inc., Tokyo, Japan) before and after the water immersion. A finite-element model was also created to examine the time course of stress accumulation during the sheet forming process using Finite Element software. Longitudinal deformation was smaller in the laminated MGs than in the single-layer MGs in the anterior area ( P  < 0.05). Finite element method (FEM) analysis also showed the largest stress accumulation in the anterior incisal area where deformations were mainly observed. Laminated double layer MGs have advantages over single-layer MGs in terms of longitudinal stability due to lower stress accumulation during the fabrication process.     

Lipoprotein abnormalities in survivors of cerebral infarction with a special reference to apolipoproteins and triglyceride-rich lipoproteins

Serum lipid and apolipoprotein concentrations were measured in 37 male survivors of cerebral infarction (CI) and in 30 healthy controls. Both groups had similar total cholesterol levels, but the HDL-cholesterol level was significantly lower and the serum triglyceride level was significantly higher in the CI patients than in the controls. The ApoB level was significantly higher in the CI patients but there was no significant difference between the 2 groups in the levels of the other apolipoproteins (ApoA-I, A-II, C-II, C-III, and E). The HDL-cholesterol/ApoA-I ratio was significantly lower in the CI patients. Both the VLDL-triglyceride and VLDL-cholesterol levels were higher in the CI patients but the VLDL-cholesterol especially its cholesterol ester level was conspicuously high. A population of VLDL particles that bound to heparin on heparin-Sepharose columns was increased in the CI patients. We suggest that cholesterol ester is excessively transferred from HDL to VLDL during the disturbed catabolism of VLDL in CI patients.     

Subretinal neovascularisation and snow banking in a case of sarcoidosis: case report.

A 49-year-old Japanese man presented with chronic granulomatous uveitis in his left eye. Later he developed macular subretinal neovascularisation. The chest x-ray showed bilateral hilar lymphadenopathy. Bronchoscopy and gallium-67 scanning were positive, PPD skin test negative, and serum angiotensin converting enzyme (ACE) levels increased. Ophthalmoscopy and fluorescein angiography of the left eye showed perivasculitis, retinochoroidal exudates, snow banking, and vitreous opacity. On these findings, the diagnosis of sarcoidosis was made. Treatment was based on topical corticosteroids, mydriatics, beta blockers, and oral carbonic anhydrase inhibitors. After 15 months the visual acuity decreased in the left eye, and a neovascular membrane was observed in the macula. Fluorescein angiography confirmed subretinal neovascularisation. Almost two years later the patient still has the neovascular membrane in his left eye.     

SUCCESSFUL ENDOSCOPIC CLOSURES OF COLONIC PERFORATIONS REQUIRING ABDOMINAL DECOMPRESSION AFTER ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY COLON CANCER

Endoscopic submucosal dissection (ESD) for colorectal cancer is not widely accepted because of its technical difficulty and the risk of perforation. In addition, the risk of peritonitis cannot be completely eliminated even if a perforation is closed successfully. Reported here are two cases of early colon cancer in which the patients sustained iatrogenic perforations of the ascending colon during conventional endoscopic mucosal resection and of the sigmoid colon during ESD, respectively, requiring abdominal decompression with an 18 G Medicut needle. Both of these perforations were successfully treated by endoscopic clipping. In conclusion, conservative medical management may be possible in patients who have undergone successful closure of colonic perforations using endoscopic clipping. In order to perform immediate endoscopic closure, abdominal decompression has been useful to decrease patient discomfort and colonic lumen collapse. Now, CO₂ insufflation is being used effectively for the prevention of pneumoperitoneum.