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PubMed1998

Effects of endoscopic variceal ligation on oxygen transport and the arterial lactate levels in patients with cirrhosis.

OBJECTIVE: Despite the increased cardiac output and oxygen delivery, an impaired oxygen uptake has been noted in patients with cirrhosis. We recently observed that endoscopic variceal ligation decreased the cardiac output due to a reduction in the cardiac preload. It is thus possible that a variceal ligation decreases the oxygen delivery and thereby negatively influences tissue oxygenation in patients receiving such treatment. We thus investigated the effects of variceal ligation on oxygen delivery, oxygen uptake, and the arterial lactate levels. METHODS: There were 22 patients with compensated cirrhosis and risky esophageal varices (Child's class A:B=13:9). Twelve patients underwent an endoscopic variceal ligation and 10 patients received gastroscopy as a control. The cardiac function, blood gas status, oxygen delivery, and arterial lactate concentration were also assessed before and after variceal ligation. The oxygen uptake was calculated by the Fick equation. RESULTS: Following variceal ligation, there was an immediate decrease in the cardiac output and oxygen delivery. The reduction in oxygen delivery was associated with a slight but significant increase in the arterial lactate concentration. The decreased oxygen delivery was also associated with a concomitant decrease in the oxygen uptake. In the control subjects, gastroscopy did not alter the systemic hemodynamics, arterial oxygen status, or arterial lactate levels. CONCLUSION: We found a significant decrease in the oxygen delivery in patients undergoing an endoscopic variceal ligation. Such deteriorated tissue oxygenation may be serious especially in patients with a low oxygen transport ability such as in patients with variceal hemorrhage with anemia. However, the clinical significance of these changes remains unclear and further studies are therefore warranted.

Aged↗
PubMed2005

Organ-specific ligation-induced changes in harmonic components of the pulse spectrum and regional vasoconstrictor selectivity in Wistar rats.

It has been shown previously that the amplitudes of the harmonic components of the pulse spectrum vary in specific patterns when the arteries leading to different organs are ligated, with the variations in the harmonics being linearly additive. Since ligation can be regarded as a vast increase in organ resistance, the present study examined the potential of using these ligation-induced variations in the pulse spectrum as reference parameters for an increase in vascular resistance and for regional vasoconstrictor selectivity. A vasoconstrictor, either arginine vasopressin (AVP) or angiotensin II (Ang II), was infused into anaesthetized Wistar rats via the femoral vein for 1 h. The distinct harmonic-specific drug effects on the pulse spectrum were simulated by combining renal artery and superior mesenteric artery ligations in different ratios, the ratio with the lowest mean square difference determining the regional drug selectivity. The ratios indicated that the effect of AVP on the pulse spectrum was attributable to the combined effect of ligating the renal and superior mesenteric arteries, while the effect of Ang II was attributable to ligation of the renal artery. The results are comparable with those of investigations of regional vascular resistance performed using traditional methods. Our findings indicate that the ligation-induced variations in the pulse spectrum can be used to determine regional increases in vascular resistance. This implies that blood pressure can be used as the sole parameter to determine which arterial bed has been affected by the vasoconstrictor, and how seriously.

Angiotensin II↗
PubMed1986

Presence of a noradrenaline uptake system on a ligated cat sympathetic nerve.

[3H]noradrenaline [( 3H]NA) uptake studies were carried out in cat hypogastric nerves ligated in vivo, 2 cm distal to the inferior mesenteric ganglion, for different time periods. Atria from the same animals served as controls to determine the uptake of the amine by the U1 uptake system present in noradrenergic nerve terminals. The net uptake of [3H]NA by hypogastric nerves increased with time of ligation, reaching a maximum 24 h after ligation in the segment of nerve immediately proximal to the ligature (P1 segment, neurosome). No further increase in uptake was observed at 48 or 72 h. Segments distal (D1) to the ligature also retained significant amounts of [3H]NA. In both cases the uptake was blocked by cocaine (3 microM). Reserpine pre-treatment (2 mg/kg I.M.) markedly decreased the endogenous NA content to 1-2% of untreated cats and the net uptake of [3H]NA was lowered to 25% both in cat hypogastric nerve and atria. The uptake was further decreased in the presence of cocaine (3 microM). 6-Hydroxydopamine (100 microM) did not modify the [3H]NA uptake by ligated cat hypogastric nerves but almost abolished the [3H]NA net uptake by right atria from the same animals. After collagenase pre-treatment (0.05% for 15 min) the net uptake of [3H]NA was not altered in the atrium. However, collagenase-pre-treated ligated nerves, took up almost twice as much [3H]NA; under these conditions, 6-hydroxydopamine produced a marked decrease in [3H]NA net uptake. These data suggest the presence in the perineurium of a diffusion barrier for very polar substances, including 6-hydroxydopamine. In conclusion, our data demonstrate that the cat hypogastric nerve ligated in vivo has a cocaine-sensitive system for NA uptake which resembles the NA uptake mechanism (U1) present in noradrenergic nerve terminals. Our data further support the view that the ligated cat hypogastric nerve (neurosome) could be considered as a model of noradrenergic nerve terminal free of effector cell.

Animals↗
PubMed1983

Comparison of infrared coagulation and rubber band ligation for first and second degree haemorrhoids: a randomised prospective clinical trial.

One hundred and thirty seven previously untreated out-patients with first and second degree haemorrhoids were allocated at random to treatment by infrared coagulation (n=66) or rubber band ligation (n=71). Complete follow up was obtained in 122 patients (60 who had undergone infrared coagulation (group 1), and 62 rubber band ligation (group 2)) at periods from three months to one year after completion of treatment. Infrared coagulation produced a satisfactory outcome in 51 patients (85%): 34 were rendered asymptomatic and 17 improved. Rubber band ligation produced a satisfactory outcome in 57 patients (92%): 33 were rendered asymptomatic and 24 improved. Both methods were equally effective in first and second degree haemorrhoids. The incidence of side effects, particularly discomfort, during and after treatment was significantly higher in those treated by rubber band ligation (p less than 0.001). This appeared to be an appreciable deterrent to future patient compliance. The number of patients losing more than 24 hours from work was higher after rubber band ligation than after infrared coagulation. The number of treatments necessary to cure symptoms did not differ significantly between the two methods. Infrared coagulation was significantly faster than rubber band ligation (p less than 0.001). Infrared coagulation is a simple, fast, and effective outpatient method for the treatment of first and second degree haemorrhoids with fewer troublesome side effects and higher patient acceptability than rubber band ligation.

Adult↗
PubMed1986

Carotid ligation: what happens in the long term?

The authors reviewed a consecutive series of 115 patients who underwent common carotid ligation during the period 1954-1984. Average follow-up was 10 years. Seventy-three (63%) patients presented following a subarachnoid haemorrhage (SAH) and 42 (36%) presented with the mass effect of an unruptured aneurysm. Thirty-nine (34%) patients were lost to follow-up of whom 27 had had a previous SAH. Forty-six (63%) of the 73 patients traced had suffered a SAH and amongst this group, 11 patients (24%) died from a proven or suspected recurrent haemorrhage within 10 years of ligation. The fatal recurrent haemorrhage rate was, therefore, 2.4%/year. Thirty (71%) of the 42 patients who presented with unruptured aneurysms were traced. Seven of these (23%) died: two following haemorrhage, 1 year and 16 years after carotid ligation and three patients died as a direct consequence of carotid ligation. Check angiographic studies were available for 55 patients following carotid ligation, a mean of 8.4 years after the procedure. Thirteen were conventional angiograms and 42 were intravenous angiograms obtained using the digital subtraction technique. Seventy-six per cent of the aneurysms visualised on the initial studies were either smaller or had apparently disappeared. Only four new aneurysms were detected and in two of these instances, the initial angiographic studies had been incomplete. The authors conclude that the annual rate of fatal recurrent haemorrhage from an intracranial aneurysm following common carotid ligation is of a similar magnitude to that of the natural history of conservatively managed ruptured intracranial aneurysms. Moreover, carotid ligation apparently does not prevent haemorrhage from a previously unruptured aneurysm and the procedure appears to carry a significant morbidity and mortality, even in patients with an unruptured aneurysm.

Adult↗
PubMed2005

Bile-pancreatic juice exclusion increases p38MAPK activation and TNF-alpha production in ligation-induced acute pancreatitis in rats.

UNLABELLED: Acute pancreatitis is associated with stress kinase activation and cytokine production. We hypothesize that bile-pancreatic juice exclusion activates p38(MAPK) and induces TNF-alpha production in ligation-induced acute pancreatitis. We compared rats with 1-3 h of duct ligation, duct ligation with duodenal bile-pancreatic juice replacement from a donor rat, and sham operation. Pancreatic homogenates were analyzed as follows: (a) Immunoblots using phospho-specific p38(MAPK) antibody showed increased p38(MAPK) activation after ligation that was inhibited by bile-pancreatic juice replacement. (b) Immune-complex kinase assay using ATF-2 as substrate showed increased p38(MAPK) activation after ligation that was subdued by bile-pancreatic juice replacement. (c) ELISA showed increased pancreatic TNF-alpha production after ligation that was significantly ameliorated by bile-pancreatic juice replacement. CONCLUSION: Bile-pancreatic juice exclusion from gut increases p38(MAPK) activation and TNF-alpha production in this experimental model. Our findings support our central hypothesis that bile-pancreatic juice exclusion exacerbates cell stress and acute inflammation in ligation-induced acute pancreatitis.

Acute Disease↗
PubMed1982

A neural factor involved in increase of the glycogen phosphorylase activity after coronary ligation in both ischemic and nonischemic areas of the dog heart.

We performed experiments to determine whether or not extracardiac factors are involved in the increase of the glycogen phosphorylase activity after coronary artery ligation in dog hearts. A branch of the left anterior descending coronary artery (LAD) was ligated for 1.5 minutes. The glycogen phosphorylase activity was determined in the endo- and epicardial layers. LAD ligation significantly increased the glycogen phosphorylase activity in both LAD (ischemic) and circumflex (nonischemic) areas. Pretreatment with reserpine (1 mg/kg, im, 24 hours before experiments) or hexamethonium (3 mg/kg, iv) prevented the LAD ligation-induced increase in the glycogen phosphorylase activity, but adrenalectomy did not. In the heart-lung preparation and stellectomized dogs, LAD ligation did not increase the glycogen phosphorylase activity in both ischemic and nonischemic areas. Changes in the glycogen phosphorylase activity in the endocardial layers were not essentially different from those in the epicardial layers. In other dogs, metabolic intermediates and ST segment of the surface electrocardiogram were measured. LAD ligation significantly decreased the tissue level of creatine phosphate and increased that of lactate in the ischemic but not in the nonischemic area. An elevation of ST segment occurred only in the ischemic area. Thus ischemic and nonischemic areas were confirmed. The ATP level, however, did not change in any of the ischemic and nonischemic areas. It is suggested that LAD ligation increases the glycogen phosphorylase activity in both ischemic and nonischemic areas probably by an increase in the efferent cardiac sympathetic nerve activity.

Adrenal Glands↗
PubMed2005

A novel gastric lesion model induced in rats by partial gastric vascular ligation.

Previous studies have suggested that histamine treatment after gastric vascular ligation induces mucosal damage in the rat stomach. Although ligation of left gastric artery and vein (L-AV) alone did not cause any damage in the stomach within 4 h, but provoked mild lesions due to ischaemia 24 h later. In the present study we demonstrated a new model of gastric lesions induced by L-AV ligation and examined the effects of various anti-ulcer drugs on this lesion model. The gastric lesions induced by L-AV ligation occurred at the corpus and antrum, especially at the corpus-antrum border, when examined 24 h later, and the severity of damage reached maximum 3 days after L-AV ligation. Repeated treatment with omeprazole or sucralfate for 3 days significantly prevented the development of gastric lesions induced by L-AV ligation, in whole mucosa, including the antrum. By contrast, famotidine given for 3 days showed a significant protection against total lesions in the whole mucosa, but had no effect on the antral lesions. Both omeprazole and famotidine dose-dependently decreased gastric acid output while sucralfate raised the intraluminal pH due to the acid-neutralizing action. These results suggest that the pathogenesis of gastric lesions induced by L-AV ligation differs depending on the region, the corpus and the antrum, and the lesions occurred in the latter area seem to be resistant to acid suppression. It is assumed that this new model of gastric lesions is useful for screening the drugs that affect gastric mucosal defense rather than acid secretion.

Administration, Oral↗
PubMed2003

A chronic heart failure model by coronary artery ligation in the goat.

The availability of a reliable heart failure model in large animals is important. We report upon our efforts to develop a chronic heart failure model in seven goats using sequential ligation of the left anterior descending (LAD) coronary artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD artery was ligated, and the diagonal vessel at the same level was ligated one hour later. Cardiac measurements were performed with a thermodilution catheter and by ultrasonography. Two months after the operation, the same measurements were made and animals were sacrificed for postmortem examinations of their hearts. Hemodynamic measurements, except cardiac output, showed no significant changes immediately after the coronary artery ligation. Echocardiographic measurements showed significant changes in the ejection fraction and fractional shortening without changes in left ventricular dimensions. Wall motion analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals immediately after coronary artery ligation. Five animals have undergone hemodynamic and ultrasonographic studies 2 months after coronary artery ligation. The results obtained from these animals showed significant increases in central venous pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure, and a significant decrease in cardiac output. Increases in left ventricular dimensions and decreases in ejection fraction with fractional shortening in ultrasonographic studies were also observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with chamber enlargement, were clearly seen with dilatation of the heart chambers in all specimens. Based on this study, we conclude that goats, like sheep, can provide a reliable model of chronic heart failure by coronary artery ligation and in view of the many advantages offered by goats, we believe that this animal model will be useful for cardiac experimentation.

Animals↗
PubMed1988

Inhibitory effect of KW-3049, a new 1,4-dihydropyridine calcium antagonist, on the reduction of myocardial creatine kinase activity and high-energy phosphate content in rats subjected to coronary artery ligation.

The effect of KW-3049, (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride on myocardial infarction in rats was examined, in comparison with some other drugs. Extension of myocardial infarction was assessed by separately determining the tissue creatine kinase (CK) activity of left ventricular free wall (LVFW) and that of interventricular septum. Loss of CK activity was limited to LVFW until 6 h after the ligation of the left main coronary artery, while 24 h after the ligation, it extended to the septum. Therefore, the effects of drugs were examined mainly in rats following 6 h of coronary artery ligation. Pretreatments with KW-3049 at 1 and 3 mg/kg (p.o.), given 1 h before coronary artery ligation, significantly reduced the loss of CK activity of LVFW by 45.3 and 39.7%, respectively. Also, posttreatment with KW-3049 at 30 micrograms/kg (i.p.), given 10 min after the ligation, significantly reduced the loss of CK activity by 30.6%. On the other hand, nifedipine (3, 10 mg/kg, p.o.), propranolol (100 mg/kg, p.o.), OKY-1581 (100 mg/kg, p.o.) and BM 13.177 (100 mg/kg, p.o.), each of which was given 1 h before coronary ligation, did not significantly reduce the loss of CK activity. Coronary artery ligation for 6 h significantly decreased the myocardial contents of adenosine triphosphate (ATP) and creatine phosphate (CP). Pretreatments with KW-3049 at 1 and 3 mg/kg (p.o.) reduced the decrease in ATP and CP. These results suggest that KW-3049 possesses a superior cardioprotective effect in comparison with the other drugs examined. The possible implications for the protection by KW-3049 are discussed.

Adenosine Triphosphate↗
PubMed1977

[Effects of pretreatment with carteolol on metabolic changes induced by coronary artery ligation in dog left ventricular wall (author's transl)].

Effects of coronary artery ligation on myocardial glycogenolysis were studied in the endo- and epicardial layers of the left ventricular wall in dogs pretreated with 10 or 100 microgram/kg (i.v.) of carteolol, a potent beta-adrenergic blocking agent. Coronary artery ligation was performed by ligating one of the small branches of the left anterior descending coronary artery. In control (saline-pretreated) dogs, an increase in phosphorylase alpha activity and an increase in breakdown of glycogen were observed in both endo- and epicardial layers after coronary artery ligation. In the presence of 10 or 100 microgram/kg of carteolol, however, increases in phosphorylase alpha activity and increase in breakdown of glycogen were not observed in either the endo or epicardial layers. These results indicate that pretreatment of the dog with carteolol inhibits the increase in glycogenolysis caused by coronary artery ligation. Nevertheless, carteolol did not completely inhibit the coronary artery ligation-induced increase in glucose-6-phosphate and lactate levels, and the coronary artery ligation-induced decrease in phosphocreatine level, particularly in the endocardial layers.

Adenosine Triphosphate↗
PubMed2005

[Viability of the spleen in rats after ligation of the splenic vessels: effects of hyperbaric oxygen therapy].

OBJECTIVE: To investigate the effects of splenic artery and vein ligation and the influence of hyperbaric oxygen after the double vascular ligation on the viability of spleen tissue. METHODS: Sixty nine adult male Wistar rats (285-375 g) were randomly separated in three groups: group 1, four rats, sham operated, group 2, 34 rats, submitted to simultaneous splenic artery and vein ligation and group 3, 31 rats, submitted to hyperbaric oxygen during 11 days, after double vascular ligation. All animals were killed on day 12 after surgery. The spleen was removed and paraffin embedded for microscopic examination. RESULTS: In the groups submitted to vascular ligation, the spleen was normal in 8.82% of rats not treated with hyperbaric oxygen and in 45.16% of rats that received hyperbaric oxygen after vascular ligation (p=0.01). In the spleens with white infarct, the mass of preserved splenic tissue in relation to the total body mass did not differ between the groups treated or not with hyperbaric oxygen. The preserved splenic tissue had normal histology in both groups. The healing process was more accelerated in the group of rats treated with hyperbaric oxygen. CONCLUSION: Results demonstrate that exposure to hyperbaric oxygen increased the frequency of total spleen mass preservation after simultaneous ligation of the splenic artery and vein but did not alter the percentage of the spleen's viable area, however the healing process in necrotic areas was accelerated.

Animals↗
PubMed1996

Rat stomach enterochromaffin-like cells are not stimulated by pylorus ligation. A biochemical and ultrastructural study.

BACKGROUND: The enterochromaffin-like (ECL) cells in the rat oxyntic mucosa produce histamine and contain cytoplasmic granules, microvesicles, and secretory vesicles. The cells respond to gastrin by the release of histamine (associated with loss of secretory vesicles), which is thought to mediate the gastrin-induced stimulation of the parietal cells. Gastric acid secretion is stimulated also by vagal excitation, which can be induced, for instance, by pylorus ligation. The present study addresses the question whether the ECL cells are involved in the acid response to pylorus ligation. METHODS: Rats were subjected to pylorus ligation and killed 4 or 16 h later. Other rats were subjected to sham operation (laparotomy). Some of the rats received human Leu15-gastrin-17 (5 nmol/kg/h) by intravenous infusion for 30 or 60 min before being killed. The serum gastrin concentration, the oxyntic mucosal histidine decarboxylase (HDC) activity, HDC mRNA concentration, histamine concentration, and gastric acid output were measured. Specimens from the oxyntic mucosa were processed for transmission electron microscopy. Electron micrographs of ECL cells were analyzed planimetrically. RESULTS: The gastric acid output was high, but the serum gastrin concentration was not affected by the pylorus ligation. The HDC activity and the level of HDC mRNA in the oxyntic mucosa were reduced, but the histamine concentration was unchanged. The secretory vesicles and granules of the ECL cells were unaffected, whereas the number and volume density of the microvesicles were reduced. Gastrin administration to sham-operated and pylorus-ligated rats lowered the oxyntic mucosal histamine concentration and increased the HDC activity in both groups. CONCLUSIONS: ECL cells in the rat stomach do not mediate the gastric acid response to pylorus ligation, and ECL cells in the pylorus-ligated stomach retain their ability to respond to gastrin with activation.

Animals↗
PubMed2005

Rubber-band ligation for hemorrhoids in a colorectal unit. A prospective study.

INTRODUCTION: Nowadays the rubber band ligation technique is one of the most worldwide used and effective treatment of the hemorrhoidal disease. OBJECTIVES: Our study has as a goal to analyze the success or failure of the rubber band ligation in hemorrhoids grade 1,2 and 3, to analyze their complications and to see if all symptomatic hemorrhoids should be treated with ligation at the first visit. PATIENTS AND METHOD: A prospective and descriptive study was designed for patients who came to the Colorectal Unit with hemorrhoidal disease from September 1997 to December 2001. First, second and third degree patients were treated according to the classification of hemorrhoids of St. Mark's Hospital. The technique of ligation after Barron was applied. RESULTS: From 261 patients with a mean age of 48.3 (range: 16-86), 181 (99 M/82 W) have been treated with Barron's method and 80 with rich fiber diet and water. Rectal bleeding was the most common symptom (91.16%). Anuscopy showed hemorrhoidal disease in all the cases. From 181 patients, 19.33% were hemorrhoids degree I, 51.93% degree II and 29.83% degree III. Two hundred and eighty-seven ligation sessions were done and the balance of ligations per patient was 2.45 and 1.5 rubber band per session. The 32% of the patients referred pain after ligation. A 13.81% of cases were operated due to persistent rectal bleeding or hemorrhoidal prolapse. CONCLUSIONS: Symptomatic hemorrhoids degree I and II with a short clinical history should be treated initially with a rich fiber and water diet. The technique of Barron is an effective therapy to treat the hemorrhoids degree 1, 2 and in 74% of success in cases with degree 3.

Adolescent↗
PubMed1999

Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation.

Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects.

Animals↗
PubMedDate not supplied

Circulating and luminal testicular factors affect LRP-2 and Apo J expression in the epididymis following efferent duct ligation.

Apolipoprotein J (clusterin or sulfated glycoprotein-2) has been shown to be secreted by the epididymal principal cells, whereupon it binds to sperm in the lumen. Apolipoprotein J also is endocytosed by principal cells along the epididymis. Recently, it has been demonstrated that low-density lipoprotein receptor-related protein-2 (LRP-2) mediates the endocytosis of Apo J and is present in the epididymis. The purpose of the present study was to determine the factors regulating the synthesis of these 2 proteins in various experimentally treated animals. The epididymides of adult rats were fixed with Bouin's fluid and examined with anti-Apo J and anti-LRP-2 antibodies by a light microscope immunocytochemical method. In normal adult animals, expression of Apo J was evident in principal cells of all epididymal regions except the proximal initial segment. Diffuse cytoplasmic staining indicated Apo J secretion. Reactive apical vesicles, presumably endosomal in nature, suggested endocytosis of Apo J. Lipoprotein receptor-related protein-2 expression was solely apical in nature and was seen as an intense apical band in principal cells of all regions except the proximal and distal initial segment and distal caput regions of the epididymis. Hypophysectomy, up to 28 days after the procedure, did not affect expression of Apo J or LRP-2 in principal cells along the entire epididymis. Orchidectomy, with or without testosterone replacement at all time intervals examined, also did not affect LRP-2 expression along the entire epididymis. This also was noted for Apo J expression in all regions except the proximal initial segment. Thus, expression of these 2 proteins does not appear to be regulated by testicular or pituitary factors. In contrast, bilateral as well as unilateral (intact and ligated sides) efferent duct ligation resulted in dramatic differences in LRP-2 and Apo J expression in principal cells in the various epididymal regions. In the case of LRP-2, a complete absence of reaction was noted in principal cells along the entire epididymis. As for Apo J, expression in the distal initial segment, intermediate zone, and caput region remained unchanged compared with that in normal adult animals, whereas in the corpus and cauda epididymides, results of cytoplasmic staining were negligible. These results suggest that under conditions of efferent duct ligation, a circulating factor emanates from the testis to inhibit expression of LRP-2 and Apo J in these epididymal regions. Furthermore, because Apo J was affected in a region-specific manner, unlike the case for LRP-2, different factors appear to be involved for each protein. These factors may be produced to inhibit proteins from being synthesized by the epididymis in the absence of luminal testicular input and may exist in cases of congenital and pathologic epididymal tubule blockages as well as after vasectomy. In the case of immunostaining for Apo J in the proximal initial segment only, normally unreactive principal cells in control adult animals became intensely reactive after orchidectomy as well as bilateral and unilateral (ligated side only) ligation. As this was not the case for hypophysectomized animals and the intact side of unilateral efferent duct-ligated animals, it is suggested that a testicular factor entering via the lumen of the efferent ducts serves to inhibit Apo J expression in this area. The present data also reveal that after efferent duct ligation, there are circulating factors that inhibit Apo J expression in a region-specific manner (corpus and cauda) and that inhibit LRP-2 expression along the entire epididymis and that these are derived from the testis. Furthermore, the data reveal that a testicular luminal factor appears to inhibit Apo J expression in the proximal initial segment of normal adult animals. Key words: Principal cells, orchidectomy, glycoprotein 330, clusterin, sulfated glycoprotein-2.

Animals↗
PubMed1976

Splenic artery ligation in selected patients with hepatic cirrhosis and in Sprague-Dawley rats.

The effects of splenic artery ligation were studied in Sprague-Dawley rats and in eight selected symptomatic patients with hepatic cirrhosis. In rats, this maneuver induced splenic infarction, reduced functional splenic mass, transiently raised platelet and reticulocyte counts and was without local complications. In seven selected patients with cirrhosis and prominent splenomegaly, the splenic artery was markedly enlarged, splenic arterial flow was greatly increased and splenic artery ligation partially lowered portal pressure. In three patients with varying cytopenias secondary to hypersplenism splenic artery ligation uniformly improved peripheral blood elements, although varying degrees of hypersplenism later recurred necessitating splenectomy in one. In five other patients, splenic artery ligation in conjunction with coronary vein ligation in four was performed for bleeding esophageal varices. Two patients later required portacaval shunting, and one other in whom operation was undertaken in desperation died of hepatic failure. Celiac-mesenteric arterioportography, operative portography, hemodynamic measurements and examination of peripheral blood elements in these eight patients suggests that splenic artery ligation in conjunction, where appropriate, with coronary vein ligation has several potentially beneficial effects. Hypersplenism may be sufficiently controlled to alleviate clinical symptoms. Arterial inflow into the portal system is reduced tending to lower portal pressure. Transheptic portal flow from the mesenteric bed is preserved. Venous anastomotic channels still functioning around the splenic pedicle and no longer draining a hyperdynamic splenic circuit may be converted into an escape route for mesenteric venous blood entering the portal system under high pressure. Nonetheless, each of these effects and their interrelationships require further study before this operation assumes a larger role in the treatment of complications of portal hypertension.

Animals↗
PubMed2001

Brain-derived neurotrophic factor increases in the uninjured dorsal root ganglion neurons in selective spinal nerve ligation model.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two major members of the neurotrophin family. Using immunohistochemistry and in situ hybridization histochemistry, we examined the effect of L5 spinal nerve ligation (SPNL), a neuropathic pain model, on the expression of BDNF in the uninjured L4 dorsal root ganglion (DRG). After L5 SPNL, both immunoreactivity for BDNF and the hybridization intensity for BDNF mRNA increased mainly in the small- and medium-sized neurons. The percentage of BDNF mRNA-expressing neurons increased in the ipsilateral L4 DRG compared with the contralateral DRG from the third to 28th day after ligation. A significantly greater number of BDNF-immunoreactive neurons were observed in the ipsilateral L4 DRG than contralateral side 14 d after ligation. To test the contribution of BDNF to the thermal hyperalgesia produced in this model, we intrathecally injected anti-BDNF antibody at third day after ligation. This treatment clearly attenuated thermal hyperalgesia for a few hours. Almost all BDNF mRNA-expressing neurons coexpressed trkA, a high-affinity NGF receptor, mRNA. The percentage of BDNF mRNA-expressing cells of trkA cells significantly increased in the ipsilateral L4 DRG 14 d after ligation. Furthermore, we examined the contribution of NGF on this phenotypic change using ELISA, Northern blot analysis, and anti-NGF antibody. NGF content in the ipsilateral L4 DRG linearly increased and reached a statistical significant level 14 d after L5 SPNL. Moreover, at this time point, the increase in NGF mRNA was observed in the ipsilateral L5 DRG and sciatic nerve, but not in the ipsilateral L4 DRG or L4 spinal nerve. Local application of anti-NGF antibody to the L4 spinal nerve beside the L5 spinal nerve-ligation site prevented the development of thermal hyperalgesia for 5 d after ligation. Our data suggest that BDNF, which increased in the uninjured L4 DRG neurons, acts as a sensory neuromodulator in the dorsal horn and contributes to thermal hyperalgesia in this neuropathic pain model. The contribution of locally synthesized NGF to thermal hyperalgesia was also demonstrated. These dynamic alterations in the expression and content of BDNF and NGF in the uninjured DRG neurons might be involved in the pathomechanisms of neuropathic pain.

Animals↗