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PubMed2002

Rho and basic fibroblast growth factor involvement in centrosome redistribution and actin microfilament remodeling during early endothelial wound repair.

OBJECTIVE: We have shown that centrosome redistribution to the front of the cell and actin microfilament remodeling occurs during the initiation of early porcine aortic endothelial wound repair even before cell migration. Because Ras homologous protein (Rho) induces actin microfilament polymerization, interacts with microtubules, and is believed to be activated by growth factors, we set forth to study the regulatory roles of basic fibroblast growth factor (bFGF) and Rho signaling on centrosome redistribution and actin microfilament remodeling in endothelial cells at an in vitro wound edge. STUDY DESIGN: With double immunofluorescent confocal microscopy, we studied the distribution of various cytoskeletal proteins in wounded porcine aortic endothelial cells in response to bFGF and exoenzyme C3 treatments. RESULTS: We showed that the addition of 10 ng/mL bFGF for 3 hours after wounding resulted in a significant increase (P <.05) in cells at the wound edge with central microfilaments oriented perpendicular to the wound. Rho inhibition with 2 microg/mL C3 resulted in the reduction of phosphotyrosine, paxillin, and central microfilament staining. Centrosome redistribution and endothelial cell elongation also were significantly inhibited (P <.05) with C3, resulting in decreased wound closure. However, inhibition was reduced with coincubation of bFGF with C3, which also returned the rate of endothelial wound closure toward control values. This Rho-independent bFGF-induced centrosome redistribution was associated with the cells showing a significant increase (P <.05) in acetylated microtubules that extended from the centrosome to the posterior cell border. CONCLUSION: We conclude that Rho regulates centrosome redistribution and central microfilament remodeling during early endothelial wound repair, and bFGF promotes actin remodeling through a downstream Rho-dependent pathway and promotes centrosome redistribution, at least in part, with a Rho-independent pathway.

Actin Cytoskeleton↗
PubMedDate not supplied

Responses of an Amazonian teleost, the tambaqui (Colossoma macropomum), to low pH in extremely soft water.

Our goal was to compare the internal physiological responses to acid challenge in an acidophilic tropical teleost endemic to dilute low-pH waters with those in nonacidophilic temperate species such as salmonids, which have been the subjects of most previous investigations. The Amazonian tambaqui (Colossoma macropomum), which migrates between circumneutral water and dilute acidic "blackwater" of the Rio Negro, was exposed to a graded low-pH and recovery regime in representative soft water (Na+ = 15, Cl- = 16, Ca2+ = 20 mumol L-1). Fish were fitted with arterial catheters for repetitive blood sampling. Water pH was altered from 6.5 (control) to 5.0, 4.0, 3.0, and back to 6.5 (recovery) on successive days. Some deaths occurred at pH 3.0. Throughout the regime, there were no disturbances of blood gases (O2 and CO2 tensions and contents) or lactate levels, and only very minor changes in acid-base status of plasma and red cells. However, erythrocytic guanylate and adenylate levels increased at pH's less than or equal to 5.0. Down to pH 4.0, plasma glucose, cortisol, and total ammonia levels remained constant, but all increased at pH 3.0, denoting a stress response. Plasma Na+ and Cl- levels declined and plasma protein concentration increased at pH 3.0, indicative of ionoregulatory and fluid volume disturbance, and neither recovered upon return to pH 6.5. Cortisol and ammonia elevations also persisted. Transepithelial potential changed progressively from highly negative values (inside) at pH 6.5 to highly positive values at pH 3.0; these alterations were fully reversible. Experimental elevations in water calcium levels drove the transepithelial potential positive at circumneutral pH, attenuated or prevented changes in transepithelial potential at low pH, and reduced Na+ and Cl- loss rates to the water during acute low-pH challenges. In general, tambaqui exhibited responses to low pH that were qualitatively similar but quantitatively more resistant than those previously documented in salmonids.

Acid Rain↗
PubMed1993

Inhibition of prostanoid synthesis depresses alveolar bone resorption but enhances root resorption in the rat.

Tooth drift requires the deformation of the root socket and the adjustment of the other components of the attachment apparatus, namely, the periodontal ligament (PDL) and the cementum. Indomethacin (7.5 mg/kg/d), an inhibitor of prostanoid synthesis, provoked in rats a depression in the bone resorption effecting the deformation of the socket (Lasfargues and Saffar, Anat. Rec., 234:310-316, 1992). In the present paper we examined the consequence of this treatment both on the PDL and the root surface. After 3 days of treatment, when osteoclastic resorption was not yet disturbed, the root had been markedly resorbed (P < 0.05) opposite the resorbing bone surface; at that time the PDL width remained in the normal range. After 7 days, i.e., when the bone resorption was depressed, the PDL was widened as the result of the ongoing root resorption. Despite the extensive root resorption, the anchorage of the PDL fibers appeared to remain effective, suggesting that it was rapidly restored. On day 14 at the time of the bone resorption recovery, cementum was deposited in the root resorption lacunae and the PDL width had returned to its control value. As early as day 3 the daily rate of dentine formation increased in the pulp area subjacent to the root resorption lacunae (P < 0.01). These data demonstrate that i) the responses of the different components of the periodontal apparatus are coordinated to allow for the maintainance of the PDL width so that when bone resorption is disturbed, root resorption compensates for it, and ii) the odontoclasts can differentiate and resorb under prostanoid inhibition whilst osteoclastic resorption of the bone socket is inhibited.

Adaptation, Physiological↗
PubMed1998

Myoelectric bowel activity in ischemia/reperfusion damage. Role of sensory neurons.

The present knowledge indicates that afferent sensory neurons (C-fibres) play an important role in the relationship between intestinal myoelectric activity (IMA) and blood flow (LDBF). The aim of this study was to evaluate the role of C-fibers in myoelectric activity of small intestine during its ischemia and reperfusion. A neurotoxin-capsaicin (CAP) was used to induce functional ablation of afferent sensory neurons. Experiments were performed on 6 groups of anesthetized rats. In the I, II, III group of rats IMA and LDBF were recorded during 100% ischemia induced by AMA 15, 30 and 60 min total occlusion and during 60 min reperfusion period. In group V and VI, IMA and LDBF were registered after intrajejunal placement of 1% CAP. In group IV we measured effects of intraluminal instillation of CAP alone. Intraluminal placement of CAP induced an early increase in slow wave amplitude SWA and slow wave frequency SWF by 35+/-11% and 19+/-10% (p<0.05) with the subsequent decrease in both by 25+/-6 and 24+/-8% (p<0.05) respectively. Short 15 min lasting ischemia induced by 100% occlusion of AMA evoked only a slight increase of SWA. During reperfusion period SWA and SWF returned to the baseline values after 15 min. Total 30 min occlusion decreased SWA and SWF by 25+/-9 and 24+/-6% (p<0.05) respectively. During reperfusion period recovery of IMA parameters to preocclusion values were slower. Intestinal hyperemia was smaller than in previous group. After 60 min lasting intestinal ischemia SWA and SWF were decreased by 58+/-7 and 40+/-6% (p<0.01) respectively. There was no return of IMA parameters to control values. These data demonstrated that intestinal ischemia induces typical changes in the bowel myoelectric activity. These changes possess their own electrical characteristics which can be used in clinical practice for evaluation of the degree ischemically-induced intestinal injury. Capsaicin pretreatment significantly decreased SWA and SWF and LDBF in comparison with those observed in group II and III during 30 and 60 min occlusion and reperfusion period. We conclude that afferent neurons C activated during mesenteric ischemia/reperfusion play an important role in protecting ischemic bowel viability.

Animals↗
PubMed1990

Non-random recirculation of small, CD4+ and CD8+ T lymphocytes in sheep: evidence for lymphocyte subset-specific lymphocyte- endothelial cell recognition.

The migratory properties of small, CD4+ and CD8+ T lymphocyte subsets have been examined in sheep under physiological conditions. Lymphocytes obtained free-floating in lymph were directly labeled with fluorochrome in vitro and returned to the blood of the same animal. Over the next 48 h the lymph collection bottles were replaced at various times. The cells in these collections, as well as an aliquot of the cells used for direct fluorescent labeling, were then phenotyped with monoclonal antibodies (mAbs) which define the mutually exclusive CD4+ and CD8+ T lymphocyte subsets in sheep. Binding of mAbs was detected by using secondary reagents labeled with a fluorochrome of a different colour. All cell samples were analyzed by flow cytometry and CD4/CD8 ratios were determined for the recirculated, fluorochrome-labeled population in each lymph collection. The mean CD4/CD8 ratio was then calculated and compared with the CD4/CD8 ratio of the intravenously infused starting population. In three experiments employing efferent prescapular lymph cells, three experiments employing efferent intestinal lymph cells and two experiments employing afferent intestinal lymph cells, the mean CD4/CD8 ratio of the recirculated, fluorochrome-labeled population was different from the CD4/CD8 ratio of the starting population, thereby indicating that non-random migration of these subsets had occurred. The finding that the CD4/CD8 ratio of the recirculated population was higher than the CD4/CD8 ratio of the transfused starting population in every case provides strong experimental support for the hypothesis that small, CD4+ T cells are extracted from the blood by specialized vascular endothelium with greater efficiency than small, CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Differential leukotriene receptor expression and calcium responses in endothelial cells and macrophages indicate 5-lipoxygenase-dependent circuits of inflammation and atherogenesis.

OBJECTIVE: Inflammatory infiltrates and atherosclerotic lesions emerge when monocytes adhere to endothelial cells (ECs), migrate into the subendothelial space, and become macrophages (MPhi(s)). Leukotrienes (LTs), products of 5-lipoxygenase, are powerful inflammatory mediators. 5-lipoxygenase+ MPhi(s) have been shown to increase during atherogenesis, and LT receptor (LT-R) transcripts were identified in diseased arteries. To investigate LT-Rs in cells involved in inflammation and atherogenesis, we used the in vitro models of human umbilical vein ECs (HUVECs) and monocyte-derived MPhi(s). METHODS AND RESULTS: HUVECs primarily expressed transcripts of the cysteinyl (cys) LT2-R, which was strongly upregulated by interleukin-4. By contrast, MPhi(s) predominantly expressed transcripts of the cysLT1-R. Calcium responses toward LTs revealed differential cysLT-R utilization by both cell types: HUVECs responded to both cysLTs, whereas MPhi(s) preferentially responded to LTD4; HUVECs, but not MPhi(s), were resistant toward a cysLT1-R antagonist, montelukast; cysLTs generated regular calcium oscillations in HUVECs that lasted >60 minutes, resulting in >500 oscillations per cell. By contrast, calcium elevations in MPhi(s) returned to baseline within seconds and were nonoscillatory. CONCLUSIONS: Our data raise the possibility that MPhi-derived LTs differentially activate cysLT2-Rs via paracrine stimulation and cysLT1-Rs via autocrine and paracrine stimulation during inflammation and atherogenesis.

Arachidonate 5-Lipoxygenase↗
PubMed1983

[Evolution of the role of women in temporary emigration in Friuli-Venezia Giulia].

Changes in the characteristics of female migrants are analyzed using data from a 1982 survey in which 1,489 returning families in the Friuli region of Italy were interviewed. "The survey identifies three main periods of this temporary emigration: the first period shows first generation migrants, whose family structure is still traditional and women's role enters into conflict with the new socio-economic reality." The second period is characterized by an increase in the percentage of married female emigrants; in the third period an increase in the percentage of single females is noted. (summary in ENG, FRE)

Demography↗
PubMed1989

The impact of immigration on the human capital of natives.

"Implications of the quantity (number) and quality (skill) of immigration on the destination economy are analyzed, including impacts on value added, wages, quasi rents, rates of return, and the skill distribution of the native labor force. Quantity-quality trade-offs are considered for both immigrant and native workers. Medium- and long-run labor-supply responses by natives to immigrant-induced changes in wage rates are shown to have second-order effects which subtantively affect the impacts of immigrants. The impact of immigration policy depends on the quality as well as quantity of immigrants, the time horizon, and the speed of factor market adjustment."

Demography↗
PubMed1984

In vivo effects of interleukin 2 on lymphocyte subpopulations in a patient with a combined immunodeficiency.

This report describes a clinical trial with Interleukin 2 (IL-2) on a 17-month old male child with combined immunodeficiency (Nezelof's syndrome). IL-2 was prepared from conditioned media of phytohemagglutinin-stimulated leukocytes from buffy coats. The purification of IL-2 involved chromatography on Matrex Blue A sepharose and gel filtration chromatography. The preparation was free of macrophage cytotoxicity factor, macrophage migration inhibition factor and colony-stimulating factor. It contained negligible activity of interferon-gamma. IL-2 activity was adjusted to 1600 U/ml, which corresponds to about 0.8 micrograms homogeneous IL-2/ml. The patient was treated over a 50-day period with a total dose of 20,000 U IL-2, which was injected subcutaneously. IL-2 was well tolerated. Within 3 weeks, the treatment led to a normalization of a lymphocytosis which had prevailed for the previous 3 months. A pronounced eosinophilia also improved but did not reach normal levels. The most striking effect was a normalization of the OKT4+/OKT8+ ratio with a concomitant relative increase in OKT3+ cells in the peripheral blood. No effects were seen on E rosette formation, B cell counts or serum Ig levels. Also NK or ADCC activity remained high, as before the treatment. Infectious episodes and requirement for antibiotic treatment were less frequent during IL-2 therapy. Some effects of IL-2 were transient, e.g., the counts of OKT4+ and OKT3+ cells which returned to pathological values a few weeks after the treatment was discontinued.

Humans↗
PubMed1982

Restitution of the surface epithelium of the in vitro frog gastric mucosa after damage with hyperosmolar sodium chloride. Morphologic and physiologic characteristics.

Frog fundic mucosas mounted in Ussing chambers between HCO-3-buffered nutrient and unbuffered secretory solutions were exposed to 1 M NaCl on the mucosal surface for 10 min. After washing and return to control solutions, transmucosal potential difference, short-circuit current, and tissue electrical resistance decreased markedly, but within 6 h these measurements had gradually returned to almost control values. A net luminal alkalinization occurred during the first 4 hours, changing into a net acid secretion of approximately 1.1 mumol . cm-2 . h-1 at 6 h. Histamine increased H+ secretion in all tissues at 8 h. In seven metiamide-treated tissues, an average alkaline flux of approximately 0.75 mumol . cm-2 . h-1 was obtained during the first 4 h after damage, decreasing to approximately 0. 40 mumol . cm-2 . h-1 during the ensuing 4 h. With HCO-3-free nutrient solution (n = 7) luminal alkalinization was decreased by about 80% 2-4 h after injury. After 1 M NaCl, the surface epithelium and gastric pit cells were destroyed and partially lifted from the gastric glands. The lamina propria between the remaining intact glands was open to the lumen or contiguous with the damaged mass of cells and mucus. During the 6 h after damage, there was a gradual process of restitution of epithelial integrity, beginning with squamous-shaped cells that appeared to be migrating from the glands and ultimately concluding with complete epithelialization by cuboidal and columnar cells. Typical junctional complexes were present between adjacent epithelial cells. The uniformity of the restoration process was such that it was possible to predict blindly in toluidine blue-stained semithin sections whether the recovery stage was short (30 min or less), intermediate (1-2 h), or advanced (4-6 h). These observations indicate that there is a very intimate correlation between the restoration of epithelial continuity and the reestablishment of secretory and electrical activity of frog gastric mucosa damaged by hypertonic NaCl in Ussing chambers.

Animals↗
PubMed1980

Lymphocyte positions in the dome epithelium of the rabbit appendix.

The apico-basal distribution of lymphocytes within the epithelium covering the domes of lymphatic tissue in the wall of the rabbit appendix was investigated in single and serial sections stained either for general histology, for cytoplasmic basophilia and acidophilia, or for nonspecific esterase activity. From the base to the summit of a dome, four zones numbered proximo-distally 1-4 were distinguished. Epithelial cells migrate from base to summit, as indicated by mitotic figures in zone 1, the gradual change from cytoplasmic basophilia to acidophilia in zones 2 to 4, and visible extrusion of cells from zone 4 at the summit. Zone 1 was free of lymphocytes. Most of the lymphocytes in zone 2 were intercellular and randomly arranged, but a few in this zone were within tapered epithelial cells modified by a process extending basally to the basement membrane. Small numbers of these tapered epithelial cells also occurred in zone 3. The large clusters of ten to 12 lymphocytes that characterized zone 3 were intercellular and impinged the apical regions of epithelial cells. Serial sections at the level of the distal cluster of zone 3 showed lymphocytes located also more basally, and some of these lymphocytes appeared to be passing through the basement membrane back into the lymphoid tissue of the dome. Epithelium of zone 4 over the distal surface of a dome was largely free of lymphocytes. Apparently most infiltrating lymphocytes form intercellular clusters and then return to the subepithelial lymphatic tissue.

Animals↗
PubMed2006

Prediction of bird-day carrying capacity on a staging site: a test of depletion models.

1. The carrying capacity of a site for migratory water birds, expressed in bird-days, can be of particular conservation value. Several attempts have been made to model this carrying capacity using ideal free distribution models such as, for instance, depletion models, in which the distribution is fully determined by exploitative competition. 2. In the tests of depletion models carried out so far, no alternative models were compared; rather, one specific model was tested. We tested whether bird-days were more in accordance with birds depleting the food resource (a1) until a critical food density which just enabled survival or (a2) until a threshold food density which renders the site as profitable as an alternative site; and birds (b1) satisfying their daily requirements or (b2) maximizing daily intake. 3. We studied Bewick's swans feeding on below-ground tubers of fennel pondweed in one part of an autumn staging site. In most years between 1995 and 2005, we measured tuber biomass densities around September, November and March, and counted swans daily during their stopover in October. 4. The best fit between observed and predicted bird-days was obtained by assuming that the swans were maximizing their daily intake and depleting the tubers until a threshold biomass density (which yielded the same energetic return as the alternative food source after accounting for a small part of the initial tuber biomass being out of reach of the swans). Also in line with daily intake maximization, the daily feeding time did not differ from 10 h day(-1), the value predicted for Bewick's swans based on their feeding costs. 5. Our results suggests that the applicable model to calculate carrying capacity may depend strongly on whether birds use a site to stopover or to winter, because it determines whether the birds are more likely to use a threshold or critical food density, and to behave as energy maximizers or satisficers.

Animal Migration↗
PubMed1996

Did the decline continue? Comparing the labor-market quality of United States immigrants from the late 1970s and late 1980s.

"The issue addressed in this paper is whether or not the decline in immigrant labor-market quality in the U.S. observed in the late 1960s and 1970s continued in the 1980s." The data are from the Immigration and Naturalization Service and are provided for the years 1979-1980 and 1989-1990. "Given the rise in earnings inequality that has occurred in the United States over the 1980s, the returns to immigration for the more highly skilled will have increased relative to the low skilled, ceteris paribus. For this reason, it is possible that the skill decline of immigrants may have halted in the 1980s as immigrants of differing skill levels respond to the altered circumstances they would face in the United States. The empirical results show that the skill decline did indeed halt...."

Americas↗
PubMed1998

Complications of retained internal bolster after pediatric percutaneous endoscopic gastrostomy.

PURPOSE: Percutaneous endoscopic gastrostomy (PEG) has been widely accepted as an efficacious means of nutritional support in the infant and child. A well-described technique uses the Gauderer-Ponsky tube (CR Bard Incorporated, Tewksbury, MA) drawn antegrade through the gastric wall and secured by an internal and external SILASTIC (Dow Corning; Midland, MI) bolster. The majority of reported complications attendant to its use occur secondary to insertion. This report details a less well-described complication of tube removal. METHODS: Since 1992, 234 pediatric PEGs have been performed using a Gauderer-Ponsky tube. Approximately 6 weeks after the procedure, all catheters were removed and replaced with gastric buttons. The internal bolster was left within the stomach to pass spontaneously. RESULTS: Five children (2.1%), ages 6 months to 5 years, failed to pass this crossbar. Three subsequently presented with dysphagia and drooling with the internal bolster wedged in the proximal esophagus. All were left with significant residual stricture after endoscopic removal of the crossbar. Two required dilatation and the third underwent operative stricturoplasty. A fourth child returned with intermittent gastric outlet obstruction. The internal bolster was retained in the stomach 4 months after catheter removal. Endoscopic retrieval resulted in resolution of the symptomatology. The final case was found to have an asymptomatic bolster in the stomach approximately 18 months after catheter removal. CONCLUSIONS: These cases highlight a potential sequelae of pediatric percutaneous endoscopic gastrostomy not previously acknowledged. The significant complications associated with the retained bolster in four of these five children suggests that follow-up should be altered to monitor prompt passage of the crossbar after tube removal.

Child, Preschool↗
PubMed1988

Judgment, 1 June 1988.

The defendant was the boyfriend of a woman who erroneously believed herself to be pregnant and decided to have an abortion. He rented a car and drove her from the Federal Republic of Germany to the Netherlands where the abortion took place. Upon their return, he was charged with violation of the law for helping a woman to have an illegal abortion. The Court convicted him, concluding that he had encouraged his girlfriend to make the decision to have an abortion and had driven her to the Netherlands for that purpose. It ruled that the fact that she was not pregnant had no bearing on his commission of the crime. It sentenced him to pay a fine of DM 600.

Abortion Applicants↗
PubMed2001

Acquisition and alteration of adhesion molecules during cultured human mast cell differentiation.

BACKGROUND: Mature human mast cells express several types of adhesion molecules on their surface. Interactions between extracellular matrix (ECM) and adhesion molecules may be important for the migration and localization of mast cells and their precursors in tissues. Little is known about the regulation of adhesion molecules on mast cells during their differentiation. OBJECTIVES: To clarify the evolution of adhesion phenotype and function, we examined the expression of adhesion molecules during cultured human mast cell (CHMC) differentiation and tested adhesion of mature CHMCs to various ECM proteins. METHODS: CHMCs were obtained by culturing human cord blood-derived CD34(+) cells in the presence of stem cell factor and IL-6. Indirect immunofluorescence and flow cytometry was used to study cell surface expression of adhesion molecules and other markers. Mature CHMCs were tested for adhesion molecule function with immobilized matrix proteins. RESULTS: At 1 week of culture, cells expressed CD11a, CD18, CD29, CD49d, and CD49e. At 14 weeks of culture, more mature CHMCs expressed CD11b, CD11c, CD29, CD49b, CD49c, CD49d, CD49e, CD51, CD61, and CD54 and weakly expressed CD18 and CD11a. CD11c, CD51, and CD61 appeared de novo by 4 weeks of culture, whereas CD49b and CD49c appeared by 8 weeks. CD29 decreased at 4 weeks but returned to the identical levels of 1-week-old cells by 8 weeks. Compared with levels at week 1, the levels of CD11a, CD18, CD49d, and CD49e at 4 weeks and beyond decreased during culture. Expression of CD49a, CD49f, and alphad integrin was never detectable during CHMC differentiation. Fourteen-week-old CHMCs significantly adhered to the leucine-aspartic acid-valine-containing connecting segment 1 fragment of fibronectin, the 120-kd argine-glycine-aspartic acid-containing fragment of fibronectin, vitronectin, and laminin through specific integrins. CONCLUSION: Expression of integrins and CD54 is differentially regulated during CHMC differentiation, and mature CHMCs can adhere to many ECM proteins. These changes may facilitate emigration from the bone marrow into the circulation and ultimately contribute to the tissue homing and localization pattern seen with mature mast cells.

Cell Adhesion↗
PubMed1992

Laparoscopic cholecystectomy in children: initial experience and recommendations.

Our initial experience with laparoscopic cholecystectomy in children and the modification of techniques required for pediatric surgical patients is reported. Six children aged 6 to 17 years underwent laparoscopic cholecystectomy for symptomatic cholelithiasis. All patients had biliary colic and did not require concomitant intraabdominal surgical procedures. Average operative time was 89 minutes; none were converted to open cholecystectomy. One patient returned home the evening of surgery, two patients were discharged the following morning, and two patients were discharged 2 days following the procedure because of their distance from home. There were no complications. All patients have remained asymptomatic on follow-up of 1 to 5 months. Based on this initial experience, several changes in the technique as reported in adults are recommended. Due to the softness and laxity of the anterior abdominal wall, an infraumbilical incision for the 10-mm camera trocar is more cosmetically acceptable and just as efficient. There is a smaller intraabdominal space with which to work, tempting one to overinflate the abdomen for better visualization. Care should be taken to ensure that the intraabdominal pressure does not exceed 15 mm Hg despite the small volumes required to do so. Placement of the second epigastric incision is more inferior and lateral than the standard recommendation for adults. The cystic duct must be controlled as early as possible in the operative course to prevent egress of stones from the gallbladder into the common duct. In one patient, these migrating stones were milked back into the gallbladder and a second clip placed.

Adolescent↗
PubMed2003

Differential salutary effects of nonselective and selective COX-2 inhibitors in postoperative ileus in rats.

BACKGROUND: Postoperative ileus (PI) is a common surgical complication, the treatment of which consists of supportive measures. AIM: The effects of several cyclooxygenase (COX) inhibitors and their interaction with L-arginine/nitric oxide synthase (NOS) pathway were tested in a rat PI model. METHODS: Intestinal transit was measured as Evans blue migration after skin incision, laparotomy, or laparotomy followed by evisceration and gut handling. RESULTS: In contrast to a selective inducible NOS (iNOS) blocker, L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL), N(omega)-nitro-L-arginine methyl ester (L-NAME) reversed the additional inhibitory effects of gut manipulation after laparotomy on the gastrointestinal transit (GI) in a dose-dependent, L-arginine-sensitive manner. Laparotomy and manipulations of small intestine increased blood plasma nitrites and nitrates level (NOx), an effect preventable by L-NAME. Indomethacin, resveratrol (selective COX-1 blocker), and COX-2 antagonists, nimesulide, NS-398, DuP-697, and L-752860, attenuated the additional inhibitory effects of gut manipulation following laparotomy in a dose-dependent manner. In contrast, only nimesulide, NS-398, DuP-697, and L-752860 partly, but significantly, reversed the effects of laparotomy on the intestinal transit. Administration of L-NAME subsequent to COX inhibitors abolished the salutary effects of the latter, implying that at least the synthesis of either NO or prostanoids must remain unaffected to enable a return of GI transit during the postoperative period. CONCLUSION: In addition to NO synthesized by constitutive NOS (cNOS), prostaglandins produced by both COX-1 and COX-2 participate in the pathogenesis of PI, albeit in different pathological mechanisms. Thus laparotomy stimulated COX-2 activity, whereas gut manipulation led to an excessive cNOS activity and prostaglandin synthesis by COX-1.

Animals↗