Inhibition of NO-synthase and degranulation of rat omental mast cells in vitro

Mast cell amines, platelet-activating factor (PAF), thromboxanes and leukotrienes have been shown to be released during nitric oxide-synthase inhibition in the rat intestine. Mast cells in rat isolated omentum (OMCs) or isolated from the rat peritoneal cavity (PMCs) have been used here to investigate the relationship(s) between these agents. N-nitro-L-arginine methyl ester (L-NAME, 100 μM) caused some degranulation of OMCs, but no enhancement of histamine release from PMCs. PAF (5 μM) and U46619 (1 μM) degranulated OMCs and enhanced histamine release from PMCs. Pre-treatment of the omentum with BN52021 (10 μM) inhibited degranulation of OMCs in response to L-NAME, PAF or U46619. Pretreatment with 1-benzylimidazole (5 or 50 μM) inhibited the effect of L-NAME but not that of PAF. Indomethacin (1 μM) or sodium nitroprusside (10 μM) also inhibited the effects of L-NAME, but nordihydroguaiaretic acid (30 μM) did not. In PMCs BN52021 inhibited PAF-induced, but not U46619-induced, release of histamine. These results suggest that inhibition of nitric oxidesynthase in the omentum by L-NAME allows thromboxanes to release PAF, which in turn degranulates and releases histamine from OMCs

Possible bi-directional link between ETA receptors and protein kinase C in rat blood vessels

Possible links have been investigated between activation of protein kinase C (PKC) and endothelin (ET) production by small blood vessels. Perfusion pressures were recorded from rat isolated mesenteric artery, with or without the small intestine attached, before and after addition to the perfusate of either ET-1, ET-3 or the PKC activator 12-deoxyphorbol 13-phenylacetate (DOPPA). Rises in perfusion pressure in response to ET-1 (10−8 M)or DOPPA (10−6 M) were reduced significantly by pre-treatment with either the ETA receptor antagonist PD151242 (10−6 M) or the PKC inhibitor Ro 31-8220 (10−6 M). ET-3 (10−8 M) had a significant, albeit small, effect only when the gut was still attached to the mesentery. Inthis latter preparation ET-1 and DOPPA increased the permeability of villi microvessels to colloidal carbon in the perfusate. This effect of DOPPA was reduced by pre-treatment with either PD151242 or Ro 31-8220, but the effects of ET-1 were reduced significantly only by Ro 31-8220. ET-3 (10−8 M) was without effect. The results suggest a possible bi-directional link between ETA receptors and PKC in the intestinal vasculature

Rate of perfusion modulates colloidal carbon leakage from rat intestinal microvessels in vitro

In order to investigate the effects of varying the rate of flow on endothelial integrity the rat isolated small intestinal vasculature was perfused at 1, 5, 10 or 20 ml/min with a gelatin-containing physiological salt solution (GPSS), followed by an injection of colloidal carbon suspension (CC). Significantly greater microvascular CC leakage occurred at 1 or 5 ml/min than at 10 or 20 ml/ mitt. CC leakage at the two slower rates of flow was reduced by adding red blood cells to the GPSS, suggesting that the microvascular endothelium became hypoxic when perfused with GPSS at 1 or 5 ml/min. After perfusion at 20 ml/min with GPSS containing resiniferatoxin (1 μM) or 5-hydroxytryptamine (100 μM), CC leakage was significantly lower than after similar perfusion at 10 ml/min. Two nitric oxide (NO) synthesis blockers, N-nitro-L-arginine methyl ester (L-NAME, 100 μM) and methylene blue (20 μM), and an NO scavenger CPTIO (100 μM) each increased CC leakage. This suggests that NO was being produced at perfusion rates of 10 or 20 ml/min. Sodium nitroprusside (10 μM), 8-bromo-cGMP (100 μM) and BN52021 (10 μM) each significantly reduced CC leakage in the presence of L-NAME

Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro

Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 μM) or indomethacin (1 μM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls. Pre-treatment with sodium nitroprusside (10 μM) significantly reduced the effects of both L-NAME and indomethacin, whereas carbacyclin (1 μM) only reduced the effects of indomethacin. PD151242 (1 μM) showed some antagonism towards the effects of L-NAME, but nordihydroguaiaretic acid (3 μM) was inactive. Pre-tment with cyproheptadine (10 μM) reduced the effects of both L-NAME and indomethacin, and also significantly reduced background (control) colloidal carbon leakage. Small intestines from polymixin B-treated rats showed significantly reduced colloidal carbon leakage in response to L-NAME. This suggests that the leakage-enhancing effects of both L-NAME and indomethacin in this preparation may be mediated by mast cell-derived amines

Percutaneous transhepatic cholangiography and biliary drainage after liver transplantation: A five-year experience

Evaluation of the biliary tract by percutaneous transhepatic cholangiography (PTC) is often required in liver transplant patients with an abnormal postoperative course. Indications for PTC include failure of liver enzyme levels to return to normal postoperatively, an elevation of serum bilirubin or liver enzyme levels, suspected bile leak, biliary obstructive symptoms, cholangitis, and sepsis. Over a 5-year period 625 liver transplants in 477 patients were performed at the University Health Center of Pittsburgh. Fifty-three patients (56 transplants) underwent 70 PTCs. Complications diagnosed by PTC included biliary strictures, bile leaks, bilomas, liver abscesses, stones, and problems associated with internal biliary stents. Thirty-two percutaneous transhepatic biliary drainage procedures were performed. Ten transplantation patients underwent balloon dilatation of postoperative biliary strictures. Interventional radiologic techniques were important in treating other complications and avoiding additional surgery in many of these patients. © 1987 Springer-Verlag New York Inc

On malfunctioning software

Artefacts do not always do what they are supposed to, due to a variety of reasons, including manufacturing problems, poor maintenance, and normal wear-and-tear. Since software is an artefact, it should be subject to malfunctioning in the same sense in which other artefacts can malfunction. Yet, whether software is on a par with other artefacts when it comes to malfunctioning crucially depends on the abstraction used in the analysis. We distinguish between “negative” and “positive” notions of malfunction. A negative malfunction, or dysfunction, occurs when an artefact token either does not (sometimes) or cannot (ever) do what it is supposed to. A positive malfunction, or misfunction, occurs when an artefact token may do what is supposed to but, at least occasionally, it also yields some unintended and undesirable effects. We argue that software, understood as type, may misfunction in some limited sense, but cannot dysfunction. Accordingly, one should distinguish software from other technical artefacts, in view of their design that makes dysfunction impossible for the former, while possible for the latter

Should the surgeon or the general practitioner (GP) follow up patients after surgery for colon cancer? A randomized controlled trial protocol focusing on quality of life, cost-effectiveness and serious clinical events

This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00572143.© 2008 Augestad et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited