Biomedical subjects

F Y Lee

Publications and source records attributed to F Y Lee.

At least 109 records · Page 6Linked to original sources

PubMed1998

Severe colonic complications in acute pancreatitis.

BACKGROUND: Colonic complications in patients with acute pancreatitis may be very severe and have rarely been analyzed in Chinese patients. METHODS: We retrospectively evaluated 1,637 patients with acute pancreatitis who were admitted to the Veterans General Hospital-Taipei from January 1986 to December 1995 in order to identify those with severe colonic complications. The clinical, radiologic and pathologic features and surgical findings in these patients are reviewed. RESULTS: Eight of 1,637 patients with acute pancreatitis had severe colonic complications. Six of them were diagnosed between two and eight weeks after the onset of clinical pancreatitis. All had a Ranson's score of at least 3. Four patients, including one with hematochezia, had a strong positive reaction for occult blood in stool specimens. Computed tomography (CT) revealed necrotizing pancreatitis and colonic wall swelling in all eight patients. Colonic involvement was discovered by CT in two patients prior to surgery, one with colocutancous fistula and the other with colonic perforation. The other six patients were found to have colonic involvement incidentally at the time of laparotomy. All of the colonic involvements were located near the splenic flexure. In addition to necrosectomy, three patients underwent segmental hemicolectomy and the remaining five patients had simple closure of the perforation. Diverting loop ileostomy or colostomy was also carried out in all patients. Three patients (34%) died of overwhelming sepsis superimposed on the subsequent multiple organ failure between 44 and 122 days after the onset of pancreatitis. CONCLUSIONS: Severe colonic complications of acute pancreatitis are rare. Although preoperative diagnosis is difficult, CT may be helpful to make an early diagnosis. These complications should be suspected in patients with severe acute pancreatitis when acute lower gastrointestinal hemorrhage or positive stool occult blood is found two to eight weeks after the onset of pancreatitis or when CT reveals necrotizing pancreatitis and colonic wall swelling; this will allow early surgical intervention.

Acute Disease↗

PubMed1997

The endocrine mechanism of sex reversal in the protandrous black porgy, Acanthopagrus schlegeli: a review.

Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite, is a functional male for the first 2 years of life but begin to sexually reverse to female after the third year. This sex pattern provides a very good model to study the mechanism of sex reversal in fish. The gonad at 5 month of age consisted of testicular tissue with few primary oocytes at 5 month of age. The ovarian tissue became dominant at 18 months of age during the non-spawning season. Testicular and ovarian tissues were separated by connective tissue. Plasma estradiol-17 beta(E2), vitellogenin and 11-ketotestosterone (11-KT) profiles in males were significantly different from those in the 3-year-old reversing females. Peak levels of plasma E2 in the reversing females occurred during the early prespawning season (in October). Lower levels of plasma E2 were, however, observed in the males. Plasma 11-KT levels significant decreased but no changes of plasma testosterone were detected in the reversing females. Exogenous E2 suppressed the testicular development but induced the gonadal aromatase activity, ovarian development and sex reversal in 2-year-old black porgy. Exogenous T and LHRH analog did not have effects on the sex reversal. Higher concentrations of pituitary GtH II and mRNA of GtH II-beta subunit were detected in the reversed females. These data suggested that E2 and gonadal aromatase closely associated to the occurrence of sex reversal. A working model of the sex reversal in black porgy is proposed.

Animals↗

PubMed1997

YC-1, a nitric oxide-independent activator of soluble guanylate cyclase, inhibits platelet-rich thrombosis in mice.

YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, has been shown to inhibit platelet activation and aggregation in vitro through the generation of cGMP. In the present study, we assessed the antithrombotic effect of YC-1 in models of experimental thrombosis in mice. YC-1 (10, 30 micrograms/g, i.p.)-treated mice showed a prolonged tail bleeding time 30 min after injection (from control 91.0 +/- 6.4 s to 208.6 +/- 22.7 s and 291.8 +/- 42.4 s, respectively). In contrast, aspirin at a dose of 30 micrograms/g (i.p.) prolonged the bleeding time to more than 600 s. Platelet-rich thrombus formation was induced by irradiation of the mesenteric venule with filtered light in mice pretreated intravenously with fluorescein sodium. YC-1 (30 micrograms/g, i.p.) markedly prolonged the occlusion time of irradiated venules (from control 146.1 +/- 19.0 s to 275.6 +/- 24.5 s) in heparinized (1 U/g) mice. In the same condition, aspirin (100 micrograms/g) only slightly prolonged the time required for occlusion (193.2 +/- 13.2 s). In a model of fatal pulmonary thromboembolism induced by intravenous injection of ADP (300 micrograms/g), YC-1 was effective in reducing mortality when administered intraperitoneally at doses of 10-30 micrograms/g. The antithrombotic effect of YC-1 was correlated with the inhibition of ADP-induced platelet aggregation ex vivo. In contrast, aspirin (30, 100 micrograms/g) did not inhibit ADP-induced pulmonary thromboembolism in vivo or platelet aggregation ex vivo. YC-1 (3, 10 micrograms/g) also exhibited profibrinolytic activity ex vivo, as revealed by shortening of the euglobulin clot lysis time. Therefore, YC-1 is an effective antithrombotic agent in preventing thrombosis in animal models, and its antiaggregating and additional profibrinolytic effects may be of potential clinical benefit in the treatment of thromboembolic diseases.

Adenosine Diphosphate↗

PubMed1997

Regional and temporal changes in the acoustic properties of fracture callus in secondary bone healing.

Controlled fractures were created in the right femora of 17 male Sprague-Dawley rats. The fractured limbs were harvested at 2, 4, 6, and 8 weeks after fracture, fixed, and embedded in polymethylmethacrylate. Midsagittal sections from each animal were evaluated with a scanning acoustic microscope, a device that generates an acoustic impedance map of the scanned material. The impedance of the fracture callus was measured in six regions on each specimen. These regions were chosen in an effort to distinguish between the impedance of the callus formed through intramembranous or endochondral ossification, and we found that the time course of increasing impedance differed for the fracture callus formed through the two pathways. Additionally, we found a significant difference in the mean impedance of the callus at each time period (p < or = 0.0013 for all comparisons), which resulted in an extremely linear relationship (r2 = 0.999) between mean callus impedance and healing time. This experimental model has become a popular choice for the investigation of fracture healing. As such, an accurate determination of the mechanical properties of the fracture callus is often sought. We propose that the implementation of scanning acoustic microscopy in the study of fracture healing may determine the changes in the material properties more accurately than conventional testing methods.

Acoustic Impedance Tests↗

PubMed1997

Isolation and characterization of the female-specific protein (vitellogenin) in mature female hemolymph of the freshwater prawn, Macrobrachium rosenbergii: comparison with ovarian vitellin.

Purification and characterization of the female-specific protein (vitellogenin) from the hemolymph of mature female prawn, Macrobrachium rosenbergii, were the objectives of this study. The comparison of biochemical characteristics between vitellogenin and ovarian vitellin was also conducted. Hemolymph vitellogenin was purified with DEAE, hydroxylapatite, and another DEAE chromatographic column. The specific protein (vitellogenin) was shown in the fractions of chromatographic columns on the basis of ELISA, Western blotting, and immunoprecipitation. A purified vitellogenin was obtained with an apparent molecular weight of 700 kDa as determined by PAGE. The purified vitellogenin was considered as a lipoglycoprotein on the basis of staining data. Three subunits (170, 100, and 89 kDa) in purified vitellogenin and two subunits (100 and 89 kDa) in vitellin were detected with SDS-PAGE. Nondisulfide bonds were found in the binding of polypeptide subunits. Only the 89-kDa subunit was a glycopolypeptide in both vitellogenin and vitellin. The amino acid composition of vitellogenin differed from that of vitellin in a few amino acids. Eight amino acid sequences from the N-terminal end of 89- and 100-kDa subunits were determined and they were identical between vitellogenin and vitellin. Seven amino acid sequence from the N-terminal end of the 170-kDa subunit were also identical to the 100-kDa subunit. Purified vitellogenin was more susceptible to precipitation in a solution with low ionic strength than vitellin. This study suggests a close relationship between vitellogenin and vitellin in M. rosenbergii in their biochemical characteristics.

Animals↗

PubMed1997

Preclinical antitumor activity of water-soluble paclitaxel derivatives.

PURPOSE: Five water-soluble paclitaxel derivatives were extensively evaluated for their antitumor activities relative to the parent drug. METHODS: Both subcutaneous (s.c.) murine (M109 lung) and human (A2780 ovarian, L2987 lung) tumor models were used for this purpose. RESULTS: Consecutive daily intravenous (i.v.) paclitaxel therapy of mice bearing s.c. M109, beginning on day 4 or 5 posttumor implant and continuing for 5 days, resulted in a range of maximum gross log cell kill (LCK) values (reflective of delays in tumor growth) and maximum relative median survival time (% T/C) values (reflective of increases in lifespan) of 1.0-2.1 and 132-162% (and one outlying result of 235%), respectively. Against the same tumor model, using the same treatment schedule, each of the water-soluble derivatives was active, with maximum LCK of 1.3-2.5 and T/C of 124-254%. These LCK and %T/C values were always within 0.5 LCK and 15%, respectively, of the concomitantly obtained maximum effects of paclitaxel. When tested in several experiments against staged (50-100 mg) s.c. A2780 tumors, using various i.v. treatment schedules, the water-soluble derivatives achieved a maximum LCK of 1.4-3.8. Evaluated in parallel, paclitaxel achieved a maximum LCK of 2.1-4.5 following every other day x 5 i.v. therapy. When paclitaxel was assayed in several experiments using the staged (50-100 mg) s.c. L2987 tumor model, maximum LCK of 0.9->4.1 were produced following every other day x 5 i.v. therapy. Concomitant testing of the water-soluble derivatives, using the same i.v. treatment schedule, resulted in maximum LCK of 0.2->4.1. In each of the tumor models used, the consistently active, and usually the most active, water-soluble derivative was BMS-185660. The levels of activity observed were comparable (within 1 LCK) to those achieved concomitantly using paclitaxel, and its potency was only slightly inferior to the parent drug. CONCLUSIONS: Based on the evaluations performed in three distal site tumor models, we conclude that BMS-185660 is a water-soluble paclitaxel derivative with preclinical antitumor activity comparable to that of the parent drug.

Animals↗

PubMed1997

Analysis of the T cell receptor V beta repertoire in human aortic aneurysms.

Human aortic aneurysm is commonly characterized by the presence of advanced atherosclerosis associated with variable chronic adventitial inflammation. Histological examination of human aortic aneurysmal specimens revealed the presence of plasma cells and lymphoid aggregates in media and adventitia of the vessels. Immunostaining further demonstrated that CD3-positive T lymphocytes are present in follicles. Using a highly sensitive reverse transcription-polymerase chain reaction amplification method, the T cell receptor (TCR) V beta gene expression in aortic aneurysms was shown to be polyclonal. Furthermore. there was no preferential expression of any TCR V beta gene in the aortic tissue as compared with that in peripheral blood in aneurysmal patients. These results indicate that the TCR repertoire in aortic aneurysm is not restricted.

Aged↗

PubMed1997

Effects of long-term administration of octreotide on sodium retention and atrial natriuretic peptide in carbon tetrachloride-induced cirrhotic rats.

BACKGROUND/AIMS: To realize the roles of peripheral vasodilatation and atrial natriuretic peptide in the formation of cirrhotic ascites, the effects of long-term administration of octreotide on carbon tetrachloride-induced cirrhotic rats were evaluated. METHODS: Urine sodium excretion, hemodynamics, plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations were compared between cirrhotic and control rats (protocol 1); and between octreotide- (65 micrograms/kg, twice daily for 10 days, subcutaneously) and placebo-treated (5% dextrose) cirrhotic rats (protocol 2). In an in vitro experiment, right atrial tissue of cirrhotic rats was incubated with different concentrations of octreotide to evaluate the release of atrial natriuretic peptide (protocol 3). RESULTS: Cirrhotic rats had significantly lower urine sodium excretion and systemic vascular resistance, and significantly higher plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations than control rats. Compared with placebo-treated cirrhotic rats, octreotide caused increased urine sodium excretion (-10 +/- 4% vs. 13 +/- 8% from baseline values, p < 0.05) and systemic vascular resistance (2.6 +/- 0.1 vs. 3.3 +/- 0.3 mmHg.min.100 g.ml-1, p < 0.05); and decreased plasma atrial natriuretic peptide levels (166.7 +/- 24.8 vs. 234.0 +/- 19.2 pg/ ml, p < 0.05), renin activities (2.45 +/- 0.49 vs. 4.36 +/- 0.53 ng.ml-1.h-1, p < 0.01) and aldosterone concentrations (290.2 +/- 40.0 vs. 483.3 +/- 82.6 pg/ml, p < 0.05). In the in vitro experiment, right atrial release of atrial natriuretic peptide of cirrhotic rats was not significantly changed when incubated with different concentrations of octreotide. CONCLUSIONS: Octreotide ameliorates renal sodium retention and suppresses plasma levels of atrial natriuretic peptide of ascitic cirrhotic rats with a novel mechanism via, at least partly, the modification of peripheral vascular resistance.

Animals↗

PubMed1997

Aminoguanidine corrects hyperdynamic circulation without ameliorating portal hypertension and portal hypertensive gastropathy in anesthetized portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertension and hyperdynamic circulation (i.e. generalized vasodilation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy. METHODS: Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (approximately 100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation. RESULTS: In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats (p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index (p<0.05) without changes in portal pressure (p>0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats (p<0.05). Treatment with aminoguanidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats (p>0.05). CONCLUSIONS: The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.

Animals↗

PubMed1997

The concentrations of vitellogenin (vitellin) and protein in hemolymph, ovary and hepatopancreas in different ovarian stages of the freshwater prawn, Macrobrachium rosenbergii.

The objectives were to measure the concentrations of vitellogenin (vitellin) and protein in hemolymph, ovary, and hepatopancreas of the freshwater prawn, Macrobrachium rosenbergii, in different stages of ovarian development. The ovarian development of M. rosenbergii was classified into five developmental stages (Stages I-V). Vitellogenin concentrations increased in the hemolymph of prawns in the early stages of ovarian development (Stage I or II) and were maintained at high levels until Stage V. There was no close association between ovarian development and the concentrations of circulating vitellogenin. Concentrations of protein in hemolymph and hepatopancreas remained constant during various stages of ovarian development. The ovarian stages closely correlated with the gonadosomatic index, the concentrations of ovarian vitellin and protein, respectively. Vitellogenin levels in hepatopancreas remained very low in different stages of the prawn although the highest levels were observed in Stage IV. No close association between hemolymph vitellogenin and ovarian vitellin was observed. The increase of vitellogenin concentration in hemolymph occurred earlier than vitellin content in ovary.

Animals↗

PubMed1997

Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan: a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment.

Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.

Adolescent↗

PubMed1997

Hyperdynamic circulation of cirrhotic rats with ascites: role of endotoxin, tumour necrosis factor-alpha and nitric oxide.

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-alpha and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-alpha and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-alpha and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats. 4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-alpha and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/ nitrite (r = 0.59, P < 0.0001) and between plasma levels of endotoxin and TNF-alpha (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-alpha and nitrate/nitrite (r = 0.24, P > 0.05). 5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.

Animals↗

PubMed1997

Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas.

Nasal T/natural killer (NK) cell lymphoma is a distinct clinicopathologic entity which is more prevalent in Asia than in America and Europe. The clonal nature of the infiltrating lymphoid cells is difficult to demonstrate because of the lack of immunologic markers for clonality and the absence of clonal T-cell receptor gene rearrangement in most cases. In this study, clonal chromosomal abnormalities were detected in the tumour cells from four patients with nasal T/NK cell lymphoma. This finding provided direct evidence for clonality of the disease. Moreover, nonrandom cytogenetic abnormalities, including isochromosome for the short arm (p) of chromosome 6, isochromosome for the long arm (q) of chromosome 1, partial deletion of 6q, and aberrations at 11q, were disclosed. Isochromosome 6p was the sole structural abnormality in one patient, which may be a pathognomonic change in nasal lymphoma.

Adult↗

PubMed1997

Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade.

Expression of the stimulatory G protein, G(S)alpha, can vary over a 3-fold range in human tissues and in rodent central nervous system. In fact, the offspring of alcoholics have higher levels of G(S)alpha expression in certain tissues compared with the offspring of nonalcoholics. The aim of this research was to test the hypothesis that a causal relationship exists between the level of expression of G(S)alpha and induction of the adenylyl cyclase (AC) cascade. The methodology employed transient transfection of HEK 293 cells with a cDNA for the 52-kDa form of G(S)alpha under regulation by inducible metallothionein promoters. Transfectants were exposed to varying concentrations (0-125 microM) of zinc sulfate that produced a 3-fold range of membrane G(S)alpha expression. The range of G(S)alpha expression produced was found to mimic a physiologically relevant spectrum of G(S)alpha expression in membranes derived from human tissues and rat brain. It was observed that induction of G(S)alpha expression increased constitutive as well as stimulated cAMP accumulation. Moreover, induction of G(S)alpha expression increased events distal to the accumulation of cAMP including the phosphorylation of the transcription factor, cAMP response element binding protein and transcriptional activation of cAMP-dependent reporter genes. In summary, these studies show that the amount of G(S)alpha expression has a marked impact on the level of activity of the AC cascade from the membrane through to the nucleus. It is hypothesized that individuals who differ in G(S)alpha expression may also differ in the expression of certain cAMP-dependent genes.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Hemodynamic studies and esophageal morphometric analyses in portal hypertensive rats with left adrenal vein ligation.

BACKGROUND: Despite many attempts to create esophageal varices in experimental animals, most of them have failed. This study investigated whether rats with partial portal vein ligation (PVL) and left adrenal vein ligation (LAL) develop hyperdynamic circulation and dilated esophageal submucosal veins as compared with sham-operated (Sham) plus LAL rats. METHODS: Two series of experiments were performed to measure (a) systemic and portal hemodynamics and (b) the cross-sectional area of esophageal submucosal veins in Sham, PVL, Sham plus LAL, and PVL plus LAL rats. Hemodynamic studies with a thermodilution technique and esophageal morphometric analyses were performed 14 days after the operation. RESULTS: PVL rats with or without LAL had a significantly lower mean arterial pressure and systemic vascular resistance accompanied by a significantly cardiac index and portal pressure than Sham rats with or without LAL (P < 0.05). LAL did not induce changes in mean arterial pressure, cardiac index, systemic vascular resistance, hear rate, or portal pressure in either Sham or PVL rats (P > 0.05). The mean cross-sectional area of esophageal submucosal veins in PVL rats with LAL (7340 +/- 833 microns2) was significantly larger than that in Sham rats with LAL (4236 +/- 556 microns2; P < 0.05). There was no significant difference in the mean cross-sectional area of esophageal submucosal veins between PVL and Sham rats without LAL. CONCLUSIONS: PVL rats with LAL developed hyperdynamic circulation similar to PVL rats without LAL. In addition, PVL plus LAL rats had larger esophageal submucosal veins than Sham plus LAL rats. This study shows that the esophageal submucosal veins of the 14-day partially portal vein-ligated rats with LAL resemble the structural abnormalities observed in human esophageal varices, suggesting that this model could be useful to investigate this entity.

Adrenal Glands↗

PubMed1997

Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide.

BACKGROUND: It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO. METHODS: Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS: Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.

Analysis of Variance↗

PubMed1997

Prognostic value of plasma endotoxin levels in patients with cirrhosis.

BACKGROUND: Endotoxemia has frequently been observed in patients with cirrhosis. Previous studies have shown that cirrhotic patients with endotoxemia have a higher mortality than those without. We evaluated the clinical value of plasma endotoxin level in predicting short-term (3 months) and long-term (2 years) survival among cirrhotic patients and compared it with the Child-Pugh score. METHODS: Plasma endotoxin levels were determined in 102 cirrhotic patients without clinical evidence of infection by a quantitative Limulus assay. The patients were followed up for 3 months to assess short-term survival and for 2 years for long-term survival. RESULTS: Plasma endotoxin levels increased progressively as liver function deteriorated. In short-term survival analysis, plasma endotoxin levels were significantly higher in non-survivors than those in survivors (10.6 +/- 2.2 pg/ml versus 5.8 +/- 0.5 pg/ml; P < 0.05). Both plasma endotoxin and serum bilirubin levels, but not the Child-Pugh score, were significant factors in predicting short-term survival in multivariate analysis. In long-term survival analysis, plasma endotoxin levels did not differ significantly between survivors and non-survivors (6.1 +/- 0.6 pg/ml versus 7.3 +/- 1.1 pg/ml; P > 0.05) and was not an independent predictor of long-term survival. In contrast, both Child-Pugh score and serum bilirubin levels were significant predictors of long-term survival in multivariate analysis. CONCLUSIONS: In patients with cirrhosis, plasma endotoxin levels progressively increase as liver function deteriorates and may be useful in predicting short-term survival.

Aged↗

PubMed1997

Hyperdynamic circulation in prehepatic portal hypertension: role of tumor necrosis factor-alpha.

BACKGROUND: Portal hypertension is associated with a hyperdynamic circulation characterized by increased cardiac output and reduced systemic vascular resistance. Tumor necrosis factor-alpha (TNF-alpha) is a peptide mediator released by mononuclear cells on activation by endotoxin, tissue injury and malignancy. This cytokine induces vasodilatation by activating nitric oxide synthesis. The aim of this study is to investigate if TNF-alpha is involved in the pathogenesis of hyperdynamic circulation observed in portal vein-ligated (PVL) rats. METHODS: Systemic and portal hemodynamics were determined in seven PVL and five sham-operated (SHAM) rats using a thermodilution technique. In addition, plasma TNF-alpha concentrations were determined in another 34 PVL and 16 SHAM rats using commercially available enzyme-linked immunosorbent assay. RESULTS: PVL rats had a significantly lower mean arterial pressure (109 +/- 17 mmHg vs. 133 +/- 12 mmHg, p < 0.001) and systemic vascular resistance (2.5 +/- 0.6 mmHg.ml-1.min.100 g BW vs. 4.6 +/- 0.8 mmHg.ml-1.min.100 g BW, p < 0.001) accompanied by a significantly higher portal pressure (14 +/- 1.9 mmHg vs. 9 +/- 2.1 mmHg, p < 0.001) and cardiac index (47.0 +/- 12.1 ml.min-1.100 g BW-1 vs. 29.3 +/- 3.5 ml.min-1.100 g BW-1, p < 0.001) when compared with SHAM rats. Also, PVL rats had significantly higher plasma levels of TNF-alpha as compared with SHAM rats (13.8 +/- 0.9 pg/ ml vs. 11.1 +/- 0.5 pg/ml, p < 0.05). CONCLUSIONS: This study suggests that elevated plasma levels of TNF-alpha observed in PVL rats may participate in the development and/or maintenance of the hyperdynamic circulation occurring in prehepatic portal hypertension.

Animals↗