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Complement component C5 deficiency reduces edema formation in murine ligation-induced acute pancreatitis.

The complement cascade is activated in humans and animals with acute pancreatitis. Activation of complement component C5 liberates C5a, C5a-desarg, and terminal complement complexes (TCCs) that increase capillary permeability, edema, and leukocyte chemotaxis at injured sites. Complement activation plays a major role in pathogenesis of capillary leak and edema formation in severe acute pancreatitis; however, the contribution of C5 (C5a/C5a-desarg, TCCs) has not been defined. Using He gene mutant mice lacking circulating C5, the role of C5 in ligation-induced acute pancreatitis was evaluated. We performed the following experiments: C5-sufficient (Hc1/Hc1) and C5-deficient (Hc0/Hc0) mice had bile and pancreatic ducts ligated. Sham-operated mice had ducts dissected but not ligated. Mice were killed at 4, 8, and 24 hr after bilepancreatic duct ligation. Serologic and morphologic evidences of acute pancreatitis were evaluated. Pancreatic edema was assessed using analysis of pancreatic water content, histologic edema score, and determination of wet weight ratio. After 4, 8, and 24 hr of bile-pancreatic duct ligation, hyperamylasemia and histologic changes of acute pancreatitis were observed in both C5-deficient and C5-sufficient mice. Edema developed in all mice with acute pancreatitis. However, when compared to C5-sufficient mice, mice deficient in C5 developed significantly less pancreatic edema at both 8 and 24 hr of bile-pancreatic duct ligation. This difference was not observed 4 hr after induction of acute pancreatitis. We conclude that C5 contributes to edema formation in murine ligation-induced acute pancreatitis. The presence of an early C5-independent phase, in conjunction with the observation of significant edema in mice deficient in C5, suggests there are other mediators of edema formation in this acute pancreatitis model.

Amylases↗

Long-term management of variceal bleeding: the place of varix injection and ligation.

Injection sclerotherapy remains the most widely used long-term management for patients after an esophageal variceal bleed. Sclerotherapy treatments should be repeated weekly until the varices are eradicated. Follow-up endoscopy every 6 to 12 months is required for life. Whenever varices recur, further weekly injection treatments are administered until re-eradication is achieved. Failure of sclerotherapy must be diagnosed early and an alternative salvage procedure performed. We currently recommend the distal splenorenal shunt. Although the complications of sclerotherapy are not great, they are cumulative with time. Unlike most surgical procedures for portal hypertension, the technique of performing sclerotherapy is not standardized, making the comparison of controlled trials difficult. The current status of controlled trials comparing sclerotherapy with other treatments is evaluated. We conclude that repeated injection sclerotherapy is at present the initial treatment of choice for patients after an esophageal variceal bleed. The technique of the new procedure of esophageal variceal ligation is described. As with sclerotherapy, weekly treatment sessions are recommended until the esophageal varices are eradicated, followed by long-term endoscopic surveillance and repeat ligation treatment when varices recur. The four controlled trials that have compared variceal ligation with sclerotherapy favor ligation. Ligation eradicated esophageal varices with fewer treatment sessions and a lower complication rate. One trial demonstrated improved survival. Complications due to the overtube are being increasingly reported but were not a problem in the controlled trials. Although esophageal variceal ligation or ligation plus sclerotherapy may ultimately prove to be superior to sclerotherapy alone, more data are required before a final conclusion can be reached.

Clinical Trials as Topic↗

Histological change in permanently clipped or ligated cerebral arterial wall. Part I. An experimental study in dogs.

In this paper, we discuss the results of a study by light microscope of the effect of permanent clipping or ligation on the intracranial arteries of 38 operation dogs and 7 control dogs. The findings obtained are: 1. In the cerebral arterial circle, necrosis could easily result from ordinary clipping or ligation because of scarce vasa vasorum. 2. As for the incidence of necrosis, the greatest was found in the case of the Yaşargil clip after electric coagulation, next came the Yaşargil clip alone, next ligation, and last the silver clip. The degree of necrosis correlated with the duration of clipping in the cases treated with a spring type clip, and was influenced more by the closing strength at the time of application in the cases with non-spring type clips or ligation. 3. In some of the cases ligated for long duration, recanalization was caused by the passage of the ligature through the vessel wall, suggesting that ligation is not a certain procedure if it is applied alone. 4. The granulation tissue round the clip and ligature began to grow after one month. As for its degree, the most marked granulation was that caused by the silver clip, next the ligature, than the Yaşargil clip after electric coagulation, and finally the Yaşargil clip used normally; in all of them the correlation with the passage of time was noted. 5. In the group of duration three months or more, concentric intimal proliferation was noted peripheral to the clip, and intimal proliferation was also noted exclusively localized to the side of a branch on the central or truncal side of a clip. This correlated in degree with the passage of time. 6. Clipping and ligation are liable to cause necrosis and fragmentation, but on the other hand it was considered that rupture of the vessel wall did not result because of the reinforcing and reparative effect of the reactive granulation tissue and the intimal proliferation which developed in such a manner as to strengthen the area involved.

Animals↗

High ligation of the greater saphenous vein for treatment of lower extremity varicosities: the fate of the vein and therapeutic results.

This study was carried out to determine the subsequent fate of the greater saphenous vein and the efficacy of its high ligation along with surgical excision or sclerotherapy of varicosities. From 1988 to 1990, 22 patients underwent high ligation and sclerotherapy, 22 underwent high ligation and varicose vein excision, and four underwent high ligation alone. There were 36 women and 12 men patients. The average patient age was 48. Sixty limbs were scanned by duplex ultrasound pre- and postoperatively to determine the status of the greater saphenous vein. Average follow-up time was 10 months. Patients and surgeons rated the results of therapy for ablation of varicosities and alleviation of symptoms. Surgical complications were evaluated. At postoperative scan, 47 greater saphenous veins (78%) were found to be completely patent, nine (15%) were thrombosed for a short segment (less than 10 cm) and four (7%) were more significantly thrombosed. Those limbs in which high ligation and sclerotherapy were performed had the highest complete patency rate (96%). Patient and surgeon satisfaction was good to excellent in every case. The only complications were three symptomatic greater saphenous vein thromboses. Although follow-up is relatively brief, complete patency of the ligated greater saphenous vein was found in most cases. High ligation allows preservation of a patent greater saphenous vein, which can be used as an arterial conduit at a later date and gives therapeutic results comparable to stripping without the additional morbidity.

Combined Modality Therapy↗

Changes in biliary excretory mechanisms in bile duct-ligated rat.

The effects of bile duct ligation on biliary excretion of bile acids, glutathione, and lipids were studied in the rat. The bile duct of the rat was ligated for three days. The biliary bile acid excretion after bile duct cannulation was higher at first, but after 90 min became lower than that in the control rat. The bile flow in the bile duct-ligated rat was higher after bile duct cannulation and gradually decreased to the same level as in the control rat. Biliary glutathione excretion, which has been suggested to be a driving force for the bile acid-independent canalicular bile flow, was markedly decreased in the bile duct-ligated rat. The mannitol clearance was increased and the bile ductules showed proliferation in the bile duct-ligated rat, suggesting an increase in the ductular bile flow. Biliary excretion of lithocholate glucuronide was more markedly impaired than that of taurocholate. When taurocholate was infused at higher rates, which increases bile flow and biliary excretion of bile acid and lipids in the control rat, biliary bile acid and lipid excretion remained constant in the bile duct-ligated rat. These findings indicate that, in the bile duct-ligated rat, the ductular bile flow was increased and bile acid-independent canalicular bile flow was decreased and that, although the biliary excretion of bile acids was not as impaired as that of organic anions, the capacity of bile acid and lipid excretion was markedly decreased.

Animals↗

Vascular pedicle ligation techniques during laparoscopic colectomy. A prospective randomized trial.

BACKGROUND: A variety of devices are available for pedicle ligation during laparoscopic colectomy including vascular staplers, clips, and electrothermal bipolar vessel-sealing devices. This study assesses their speed, reliability, and cost to guide surgeons in their choice for intracorporeal pedicle ligation. METHODS: A prospective randomized study comparing laparoscopic vascular staplers and disposable clip appliers (S/C) with the LigaSure Atlas (LIG) was performed during elective right, left, and total colectomy. Cases were stratified by procedure. Failure was defined as any bleeding after proper pedicle ligation. RESULTS: The study included 48 S/C patients and 52 LIG patients with no differences in demographics, diagnosis, procedure, number of vessels ligated per procedure, or operative time. Failure occurred for 14 (9.2%) of the 152 vessels ligated in the S/C group, as compared with 5 (3%) of the 169 vessels ligated in the LIG group (p = 0.02). The median blood loss associated with device failure was 50 ml (range, 20-50 ml) in S/C group, as compared with 100 ml (range 25-800 ml) in the LIG group (p = 0.054). Major blood loss attributable to device failure and surgeon error occurred in only one LIG case. The mean cost per case of vessel ligation was significantly less in the LIG group (317 dollars +/- 0 dollars vs 400 dollars +/- 112 dollars; p < 0.001). The cost differences were greatest for total colectomy (LIG = 317 dollars +/- 0 dollars vs S/C = 565 dollars +/- 67 dollars; p = 0.002). CONCLUSION: Device failure, although more common in the S/C group, does not result in significant blood loss. The LigaSure Atlas is more cost effective during laparoscopic colectomy, especially total colectomy, and may allow the surgeon more versatility in its application.

Adult↗

The effect of insulin-like growth factor-I on hepatocyte apoptosis after bile duct ligation in rat.

Obstructive jaundice may promote bacterial overgrowth and altered intestinal barrier function, with resultant increased translocation of endotoxin to the liver, amd thus may potentiate the phenomenon of hepatocyte apoptosis. Exogenous administration of insulin-like growth factor-I (IGF-I) has been shown to enhance mucosal adaptation after small bowel resection in rats and also to accelerate repair of small intestinal mucosa after damage by the chemotherapy drug methotrexate. The aim of the current study was to determine the effect of exogenous IGF-I administration on hepatocyte apoptosis after bile duct ligation in rat. Male Sprague-Dawley rats weighing 250-300 g were randomized to three groups (n=6 in each group). Group 1 (control; C) underwent sham operation and was simultaneously treated with the same amount of normal saline. Group 2 (obstructive jaundice; OB) underwent common bile duct ligation without other manipulation. Group 3 (obstructive jaundice with IGF-I; OBIGF-I) underwent common bile duct ligation and simultaneous treatment with recombinant human IGF-I (a total dose of 1 mg in each rat, divided into six administrations; about 1 mg/kg/day). After 3 days, liver tissue was harvested and immediately snap-frozen in liquid nitrogen for histopathologic analysis and apoptosis measurements. Compared with the sham operation group (C), increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively). There was no significant difference in hepatocyte apoptosis (P=0.925) or ductular proliferation (P=0.385) between the sham control group (C) and the OBIGF-I group. Increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively).

Animals↗

Is tubal ligation a risk factor for low bone density and increased risk of fracture?

OBJECTIVE: Osteoporosis is a major women's health problem, because it is responsible for about 1.3 million fractures in the United States each year. Estrogen deficiency is a major risk factor in the pathogenesis of osteoporosis. Recent evidence has indicated that tubal ligation may cause menstrual dysfunction and estrogen deficiency. This study examined the association between tubal ligation and bone mass in a group of elderly postmenopausal women. STUDY DESIGN: Subjects were 2215 white women > or = 65 years old participating in the Baltimore center of the Study of Osteoporotic Fractures. Bone mineral density of the proximal and distal radius and the calcaneus was measured by single photon absorptiometry. Multiple regression analysis was performed to determine whether tubal ligation had an independent effect on bone density. The effect of tubal ligation on the risk of hip and osteoporotic fractures was estimated by Cox proportional hazards model. RESULTS: Women who reported a tubal ligation had lower, although not statistically significant, bone density of the radius and calcaneus. The relative risk of hip (1.05, 95% confidence limit 0.84 to 1.32) and osteoporotic fractures (1.01, 0.80 to 1.29) was not significantly increased in women with tubal ligation. CONCLUSION: We conclude that elderly women who had a tubal ligation have small changes in bone density that are not of sufficient magnitude to increase their risk of osteoporotic fractures.

Absorptiometry, Photon↗

A possible mechanism of induction and translocation into blood stream of rat alkaline phosphatase activity by bile duct ligation.

We investigated the effects of bile duct ligation on alkaline phosphatase (ALP) activities in liver, calvarium, duodenum, and ileum in rats and its possible mechanism of action. ALP isozyme activities in the ligated rats were significantly elevated in the liver and duodenum, while those in the ileum and calvarium were markedly decreased. The ALP isozyme activity elevated by the ligation was obviously suppressed by prior administration of indomethacin, an inhibitor of prostaglandin synthesis. Moreover, phorbol ester also elevated the ALP activity as well as the phosphatase level in the ligated rat. However, other drugs, such as an inhibitor of protein kinase C and calmodulin, showed different effects: calmodulin stimulated an 11.0-, 1.3-, or 1.5-fold increase in ALP activity in the ileum, duodenum, or calvarium, respectively; whereas the hepatic enzyme activity was not affected. The induction by calmodulin was markedly different from that by the ligation. Moreover, imipramine, an inhibitor of protein kinase C, had little effect. These results suggest that prostaglandin is a possible ALP inducer in ligated rats, probably working by elevating the cAMP level. On the other hand, the ligation induced simultaneously de novo synthesis of the membranous and soluble ALP isozymes; and the release rate of the soluble enzyme was greater than that of the membranous isozymes, indicating that the soluble enzyme might be a main source of the induced serum ALP. Lectin affinity chromatography indicated that the soluble enzyme or induced serum enzyme may contain more fucose than that of the membranous one, suggesting that the sugar moiety in the ALP molecule may relate to the clearance of ALP from or its release into the circulation.

Alkaline Phosphatase↗

Effects of prolonged duct ligation of the rat salivary glands on the activity of trypsin-like protease.

The effects of ligation on body weight, protease activity and hair kynurenine content were observed. The body weights of parotid gland(PT)-ligated and of combined submandibular (SM)-, sublingual (SL)- and PT-ligated rats were much less than those of sham-operated controls. However, the weights of SM,SL-ligated rats were similar to those of controls. The activity of trypsin-like protease in the duct-ligated submandibular gland was significantly reduced to 0.3-0.7 per cent of that in controls. Protein concentration also decreased in the duct-ligated submandibular gland. Kynurenine content in the hair of duct-ligated rats was higher than that in controls.

Animals↗

Effects of portal vein ligation on sex hormone metabolism in male rats: relationship to lowered hepatic cytochrome P450 levels.

Hepatic cytochrome P450 levels in male rats fall after portal vein ligation, a procedure that produces total hepatic bypass of portal blood. The present study was undertaken to examine whether changes in sex hormone metabolism could account for these lowered cytochrome P450 levels. Portal vein ligation resulted in testicular atrophy and low serum testosterone concentrations. Serum luteinizing hormone levels were also reduced, suggesting that testicular atrophy was secondary to suppression of the hypothalamic-pituitary-gonadal axis. Serum estrone and estradiol concentrations were significantly increased after portal vein ligation, while the magnitude and delayed onset of increases in urinary total estrogen excretion suggested that this was due largely to increased estrogen production. In male rats, both castration (at 12 wk) and exogenous estrogen administration resulted in changes in hepatic cytochrome P450 levels and ethylmorphine N-demethylase activity that were qualitatively similar to those seen after portal vein ligation. In female and castrated male rats, however, cytochrome P450 was not affected by portal vein ligation. Testosterone supplementation corrected the changes of cytochrome P450 levels in castrated male rats but did not have this effect in portal vein-ligated male rats. It is concluded that changes in sex hormone metabolism do occur after portal vein ligation and may contribute to alterations in cytochrome P450 and drug-metabolizing enzyme activity. Decreased levels of serum testosterone, however, do not alone account for the changes in hepatic drug metabolism in this model, and suppression of a hypothalamic-pituitary factor appears to be important.

Animals↗

Effects of splenectomy and splenic artery ligation on the portal pressure in portal hypertensive rats.

Immediate, short-, and long-term effects of splenectomy and splenic artery ligation on the portal pressure were studied in animal models experimentally created by partial portal vein ligation. The portal pressure of these animals would usually elevate immediately after partial ligation of the portal vein from a normal level of 6.0 +/- 0.5 to 14.8 +/- 1.3 mm Hg (P < 0.005), which could be maintained at least for 6 months. The portal pressure measured at 2 weeks, 4 weeks, and 6 months after portal vein ligation was 14.0 +/- 2.7, 15.2 +/- 2.7, and 12.7 +/- 2.0 mm Hg, respectively (P < 0.005, as compared with the normal). When splenectomy was performed on these animals at 2 weeks after partial portal vein ligation, the pressure dropped immediately but only transiently from 14.0 +/- 2.7 to 11.0 +/- 3.0 mm Hg, and bounced back to the presplenectomy level in 20 sec. After an additional 2 weeks, the portal pressure in these splenectomized rats was usually at 15.2 +/- 4.2 mm Hg, which was indistinguishable from that of rats whose portal vein was ligated but the spleen was not removed. Six months after splenectomy, however, the portal hypertensive rats had a portal pressure of 17.1 +/- 6.4 mm Hg, which was significantly higher than that of the controls. Splenic artery ligation, on the other hand, did not result in any immediate decrease in portal pressure (14.0 +/- 2.7 mm Hg vs 14.6 +/- 1.4 mm Hg; P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of ligation of patent ductus arteriosus on left ventricular performance and its determinants in premature neonates.

OBJECTIVES: The purpose of this study was to determine in preterm newborn infants the effects of ductal ligation on ventricular performance and its determinants: preload, afterload and contractility. BACKGROUND: Neonatal ventricular performance is highly sensitive to afterload. Therefore, the increase in systemic vascular resistance associated with ligation of a patent ductus arteriosus might worsen ventricular performance in the preterm infant. METHODS: All 14 premature infants undergoing patent ductus arteriosus ligation in a 1-year period at our institution underwent echocardiography at three times: before, immediately after and 24 h after ligation. Indexes studied included ventricular performance (fractional area change), preload (left ventricular end-diastolic dimension), afterload (end-systolic wall stress) and contractility (the difference between the measured and predicted velocity of circumferential fiber shortening). Blood pressure was measured; systemic resistance was calculated. These data were compared with those of 14 preterm infants without patent ductus arteriosus. RESULTS: The infants with patent ductus arteriosus had higher values for ventricular performance (mean +/- SD fractional area change 60 +/- 9% vs. 52 +/- 11%, p < 0.05) and lower values for wall stress (22 +/- 6 vs. 44 +/- 17 g/cm2, p < 0.05) before ligation than did the control group. At 24 h after ligation, ventricular performance was not significantly changed (fractional area change 60 +/- 9% to 57 +/- 12%). There were significant increases in blood pressure and systemic vascular resistance but no changes in wall stress or contractility. CONCLUSIONS: Ventricular performance is higher in premature infants with than in those without patent ductus arteriosus because afterload is lower in the former group. Although ductal ligation increases blood pressure and systemic resistance, wall stress and ventricular performance are maintained. Our results suggest that the premature newborn maintains ventricular performance during stress, at least in part, by manipulating afterload.

Blood Pressure↗

A novel method for safe and accurate left anterior descending coronary artery ligation for research in rats.

BACKGROUND: Left anterior descending artery (LAD) ligation has been commonly used in rats to induce left ventricular infarction for research purposes. However, LAD ligation is a very difficult procedure with high mortality rate in rats. We have developed a safe method of LAD ligation in rats with low mortality. METHODS: Thirty-six Sprague-Dawley male rats weighing 300-350 g were selected for LAD ligation for the induction of ischemic cardiomyopathy. The surgery was performed under general anesthesia. Left-sided thoracotomy was performed by cutting the fifth and sixth ribs. The pericardium was opened, and the heart exteriorized with a cardiac holder consisting of a plastic loop (1.5x2 cm). The LAD was localized 1-2 mm below the junction of pulmonary conus and the left atrial appendage. A 5.0 silk suture was used to ligate the LAD from the left border of the pulmonary conus to the right border of the left atrial appendage. The heart was returned back to the chest and the chest wall closed with presutured lopes of 4.0 silk. RESULTS: Mid-LAD ligation was successful in all rats, with less than 5% mortality. The entire surgery was performed in less than 15 min. This method is simple and can be learned in a short period of time. Rats survived the procedure with induction of congestive heart failure for up to 3 weeks of follow-up. CONCLUSIONS: Using our method, LAD ligation can safely be performed in rats 1-2 mm below the junction of the pulmonary conus and the left atrial appendage, with a very low mortality rate.

Animals↗

Ultrasound-guided foam sclerotherapy combined with sapheno-femoral ligation compared to surgical treatment of varicose veins: early results of a randomised controlled trial.

AIM: This study is a prospective randomised controlled trial comparing sapheno-femoral ligation, great saphenous stripping and multiple avulsions with sapheno-femoral ligation and ultrasound guided foam sclerotherapy to the saphenous vein. Primary end points were patient recovery period and quality of life and secondary end points frequency of complications on the two arms of the trial and the cost of the treatment. MATERIAL AND METHOD: Sixty patients with primary varicose veins due to GSV incompetence and suitable for day case surgery were randomly allocated to undergo ultrasound-guided sclerotherapy with sapheno-femoral ligation under local anaesthesia (n=30) or sapheno-femoral ligation, stripping and multiple avulsions under general anaesthesia (n=30). The study protocol included history, physical examination, assignment of CEAP class and assessment venous clinical severity score (VCSS), completion of the aberdeen vein questionnaire (AVQ) and colour duplex ultrasound. RESULTS: All treatments were completed as intended. Median time to return to normal activities was significantly reduced in the foam sclerotherapy group (2 days) compared to the surgical group (8 days) (p<0.001, Mann-Whitney). AVQ score was also significantly reduced at 3 months by 46% in the sclerotherapy group, and by 40% in the conventional surgery group (p<0.001, Wilcoxon). The time taken to complete treatment was shorter in the foam sclerotherapy plus SFJ ligation group: 45 vs. 85 min (p<0.001, Mann-Whitney). The overall cost of the procedure in the sclerotherapy group ( 672.97 pounds) was significantly less compared to conventional surgery ( 1120.64 pounds). At 3 weeks, there was no statistical difference in the complication rate between the two groups. At 3 months, median CEAP class dropped from four pre-operatively to one following treatment in both groups and the median VCSS score dropped from five to one in group one and from seven to three in group two (p<0.001, Wilcoxon test). In group one four patients (13%) had a recanalised vein which needed further sessions of foam sclerotherapy, resulting in a short-term closure rate of 87%. CONCLUSION: Ultrasound guided sclerotherapy combined with sapheno-femoral ligation was less expensive, involved a shorter treatment time and resulted in more rapid recovery compared to sapheno-femoral ligation, saphenous stripping and phlebectomies.

Adult↗

Cyclin expression in the atrophying and proliferating lobes of the liver after portal vein branch ligation and hepatectomy in rats.

BACKGROUND: Portal vein branch ligation causes atrophy of the portal vein ligated lobes (PVL) and proliferation of the nonligated lobes (PVNL) of the liver. However, the mechanisms underlying atrophy of the PVL and proliferation of PVNL after portal vein branch ligation have not been clarified except that interleukin-6 (IL-6), nuclear factor kappa B (NF-kappaB), signal transducer and activator of transcription 3 (STAT3), and immediate-early gene expression are similarly induced in both the PVL and the PVNL. Thus, it is still unclear what factors cause the subsequent atrophy and proliferation. MATERIALS AND METHODS: Male Wistar rats were randomly separated into a portal vein branch ligation group and partial hepatectomy group. In the portal vein branch ligation group, the branch of portal vein supplying the median and left lateral lobes of the liver was ligated. In the partial hepatectomy group, the correspondent lobes of the liver were excised. We examined cyclin expression in the PVL and PVNL after portal vein branch ligation in comparison to cyclin expression in the remaining liver (HEP) after partial hepatectomy. Cyclin D1, E, and A mRNA and protein expressions were analyzed by RT-PCR and Western blotting, respectively. RESULTS: The mRNA and protein expressions of cyclin D1 and A were not up-regulated in the PVL, whereas those in the PVNL and HEP were up-regulated. Cyclin D1 mRNA and protein expressions were significantly lower in the PVL than in the PVNL and HEP at 18 h. The levels of mRNA and protein expression of cyclin A were significantly lower in the PVL than in the PVNL and HEP at 36 h. Liver regeneration, assessed by the relative liver weight, thymidine incorporation into DNA, and proliferating cell nuclear antigen (PCNA) labeling index was delayed significantly in the PVNL compared to that in the HEP. Cyclin D1 mRNA and protein expressions were significantly lower in the PVNL than in the HEP at 12 and 18 h, respectively. CONCLUSIONS: Cell-cycle progression might be inhibited at G(1)-phase accompanied by impaired cyclin D1 expression in the PVL, which results in atrophy. The fact that liver proliferation of the PVNL is delayed in comparison to that of the HEP is likely due to delayed expression of cyclin D1.

Animals↗

Bile duct ligation plus hyperammonemia in rats reproduces the alterations in the modulation of soluble guanylate cyclase by nitric oxide in brain of cirrhotic patients.

Modulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) is altered in brain from cirrhotic patients. The aim of this work was to assess whether an animal model of cirrhosis, bile duct ligation, alone or combined with diet-induced hyperammonemia for 7-10 days reproduces the alterations in NO modulation of sGC found in brains from cirrhotic patients. sGC activity was measured under basal conditions and in the presence of NO in cerebellum and cerebral cortex of the following groups of rats: controls, bile duct ligation without or with hyperammonemia and hyperammonemia without bile duct ligation. In cerebellum activation of sGC by NO was significantly lower in bile duct ligated rats with (12 +/- five-fold) or without (14 +/- six-fold) hyperammonemia than in control rats (23 +/- seven-fold). In cerebral cortex activation of sGC by NO was higher in rats with bile duct ligation with hyperammonemia (124 +/- 30-fold) but not without hyperammonemia (59 +/- 15-fold) than in control rats (66 +/- 11-fold). The combination of bile duct ligation and hyperammonemia reproduces the alterations in the modulation of soluble guanylate cyclase by NO found in cerebral cortex and cerebellum of cirrhotic patients while bile duct ligation or hyperammonemia alone reproduces the effects in cerebellum but not in cerebral cortex.

Animals↗

Hemostasis in blood vessels after ligation.

The length of time required to achieve hemostasis after ligation of blood vessels with a diameter of 1.0 to 3.5 mm was studied. Canine limb vessels were ligated with stainless steel clips. These were removed at 48, 60, 72, 84, or 96 hours after ligation, and the degree of hemostasis was evaluated by observing the effect of varying amounts of trauma applied to the vessels. The vessels were first observed for 1 minute. In the second phase the vessels were stroked for 15 seconds and then observed for 1 minute. In the second phase the vessels were stroked for 15 seconds and then observed for any bleeding. An additional 15 seconds of stroking followed by observation completed the evaluation. All blood vessels achieved hemostasis after 96 hours of secure ligation despite the trauma. All ligating devices must provide secure ligation to achieve hemostasis for at least 96 hours. The presence of disease processes or medications interfering with clotting would necessitate a longer period of secure ligation to achieve hemostasis.

Animals↗