Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats

AIM: To compare the efficacy of probiotic preparation Golden Bifid and lactulose on rat experimental model of minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). METHODS: MHE was induced by intraperitoneal injection of TAA (200 mg/kg) every 24 h for two consecutive days. Thirty-six male MHE models were then randomly divided into 3 groups: TAA group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) were gavaged, respectively with 8 mL/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination of probiotic) dissolved in 2 ml of normal saline, once a day for 8 d (from the 5th d before the experiment to the 3rd d of the experiment). The latency of brainstem auditory evoked potentials (BAEP) I was used as an objective index of MHE. The incidence of MHE, the level of serum endotoxin, ammonia, liver function and histological grade of hepatic injury of rats were examined individually. RESULTS: There were no overt HE and rat deaths in 3 groups. The incidence of MHE, the levels of blood ammonia and endotoxin in TAA group, which were 83.3% (10/12), 168.33±15.44 mg/dL and 0.36±0.04 EU/mL, respectively, were significantly higher than those in lactulose group, which were 33.3% (4/12), 110.25±7.39 mg/dL and 0.19±0.02 EU/mL, and probiotics group, which were 33.3% (4/12), 108.58±10.24 mg/dL and 0.13±0.03 EU/mL respectively (P <0.001). It showed that either probiotics or lactulose could significantly lower the level of hyperammonemia and hyper-endotoxemia, lighten centrolobular necrotic areas as well as inflammatory reaction in the liver of rats, normalize the latency of BAEP, and decrease the incidence of MHE. However, no significant differences were observed between these two groups (P>0.05). CONCLUSION: Probiotic compound Golden Bifid is at least as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE.     

Changes of serum levels of ICAM-1, IGF-1 and IL-8 in normal offspring with a family history of essential hypertension

Background Essential hypertension(EH) has become the most common chronic non-infectious epidemic and is one of the most common risk factors for the damage to heart,brain,kidney and other organs.The serum levels of ICAM-1,IGF-1 and IL-8 play important roles in the pathogenesis of EH.Methods In the medical check-up center of the Affiliated Hospital of Qingdao University Medical College,sixty normal offspring with a family history of EH were randomly recruited into two groups:30 offspring with a father or mother suffering from EH as single-parent group,and 30 offspring with both parents suffering from EH as double-parent group,and another 30 normal offspring whose parents did not suffer from EH as control group.The serum levels of ICAM-1,IGF-1 and IL-8 were determined by enzyme-linked immunosorbent assay(ELISA).Result The serum levels of ICAM-1,IGF-1 and IL-8 were significantly higher in both single-parent group and double-parent group than in the control group(P < 0.05),and the serum levels of ICAM-1,IGF-1 and IL-8 were higher in the double-parent group than in the single-parent group(P < 0.05).The serum levels of ICAM-1,IGF-1 and IL-8 were positively correlated with the severity of blood pressure elevation(r = 0.375,r = 0.465,r = 0.326,P < 0.05,P < 0.01,P < 0.05 respectively).Conclusions Due to the influence of heredity,the serum inflammatory factor contents in normal offspring with EH family history may increase before blood pressure rise.Detection of serum inflammatory factors in healthy offspring with a family history of EH could predict occurrence of hypertension,and provide a more reliable basis for the primary prevention of hypertension.     

Is ABO blood group truly a risk factor for thrombosis and adverse outcomes?

ABO blood type is one of the most readily available laboratory test, and serves as a vital determinant in blood transfusion and organ transplantation. The ABO antigens are expressed not only on red blood cell membranes, determining the compatibility of transfusion, but also on the surface of other human cells, including epithelium, platelet and vascular endothelium, therefore extending the research into other involvements of cardiovascular disease and postoperative outcomes. ABO blood group has been recognized as a risk factor of venous thrombosis embolism since the 1960's, effects now understood to be related to ABO dependent variations are procoagulant factor Ⅷ(FⅧ) and von Willebrand factor(vWF) levels. Levels of vWF, mostly genetically determined, are strongly associated with venous thromboembolism(VTE). It mediates platelet adhesion aggregation and stabilizes FⅧ in plasma. Moreover, many studies have tried to identify the relationship between ABO blood types and ischemic heart disease. Unlike the clear and convincing associations between VTE and ABO blood type, the link between ABO blood type and ischemic heart disease is less consistent and may be confusing. Other than genetic factors, ischemic heart disease is strongly related to diet, race, lipid metabolism and economic status. In this review, we'll summarize the data relating race and genetics, including ABO blood type, to VTE, ischemic heart disease and postoperative bleeding after cardiac surgery.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

克山病患者抗氧化能力测定

Objective To explore the relationship between myocardial damage and antioxidant capacity in vivo of Keshan disease patients and to analyze the possible pathogenesis. Methods In the period from 2005 to 2006, 41 chronic and latent Keshan disease cases were chosen as the case group from such serious endemic areas as Yongjin Village, Xinfa Village of Fuyu County, Fuan Village of Shangzhi County, Xinghuo Village of Wudalianchi County, 61 healthy people from the same area as internal controls, 48 healthy people from Xianglansan Village of Wangkui County, an un-endemic area, as external control. Fasting peripheral venous blood was collected from all the people. And blood selenium, glutathione peroxidase(GSH-Px) and suporoxide dismutase.(T-SOD) activities, malondialdehyde (MDA) levels were examined. Results Blood selenium level of the patient group [(34.80±13.30) μg/L], GSH-Px[(104.10±34.19)U/L]and T-SOD[(92.16±17.98)×103 U/L]actives were significantly lower than the internal control group [(41.24±13.57)μg/L, (118.57±25.49)U/L, (104.82±13.56)×103 U/L]and the external control group [(48.33±16.51)μg/L, (155.00±24.01)U/L, (108.48±12.73)×103 U/L], respectively, with a statistically significant difference(all P < 0.05). MDA level of the patient group[(7.12± 1.37)μmol/L]was higher than that in the internal control group[(5.36±1.18)μmol/L]and the external control group[(5.22±0.83)μmol/L]with a statistically significant differences(both P < 0.05). The blood selenium level, GSH-Px activity of internal control group was resoectively lower than that in the external control group, the differences being statistically significant(beth P < 0.05). Conclusions Selenium deficiency may lead to reduced antioxidant capacity and enhanced oxidative damage in Keshan disease patients in vivo. There may be a certain relationship between oxidative stress disorder and myocardial damage of Keshan disease.     

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

AIM： To study glutamine synthetase （GS） activity and glutamate uptake in the hippocampus and frontal cortex （FC） from rats with prehepatic portal vein hypertension.
METHODS： Male Wistar rats were divided into shamoperated group and a portal hypertension （PH） group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas.
RESULTS： We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity.
CONCLUSION： The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions.     

Plasma ADH levels during heart surgery.

1) Plasma ADH levels measured by bioassay in the group with extracorporeal circulation were 2.3 +/- 0.6 muu/ml before surgery and 6.6 +/- 1.8 muu/ml during anesthesia. They increased to 196.5 +/- 62.3 muu/ml or about 100 times greater than before surgery during cardiopulmonary bypass. 2) In the group without extracorporeal circulation, plasma ADH levels were 1.5 +/- 0.9 muu/ml before surgery and increased to 44.1 +/- 15.2 muu/ml during operation. 3) After operation decrease in plasma ADH level was relatively rapid in both groups. It became three times that of the control level in the morning of the next day. 4) Marked increase in plasma ADH level during cardiopulmonary bypass was much the same as it was during hemorrhagic shock in dog experiments. 5) Fall in mean arterial blood pressure and loss of pulsatile blood flow will play main roles in this marked increase in ADH during cardiopulmonary bypass through stimulation of arterial baroreceptors and probably chemoreceptors. 6) In two cases with mitral stenosis, increase in plasma ADH during cardiopulmonary bypass was lesser than the other heart diseases.     

Plasma fibronectin levels in ischemic heart disease

Fibronectin is a paradigm adhesive protein which has been implicated in the regulation of several cellular processes and cell-cell interactions. Large amounts of fibronectin have been detected in atherosclerotic plaques, while hypertension in animal models has been shown to rapidly increase fibronectin expression in arterial walls. The aim of the present study was to determine the levels of plasma fibronectin (FN) in 133 patients with ischemic heart disease and in 36 normal controls, and to investigate the possible association with blood pressure. Plasma FN levels in patients with ischemic heart disease were found to be significantly elevated (mean+/-S.D.; 46.5+/-14.2 mg/dl) compared with the control group (38.0+/-14.2 mg/dl) (P=0.002). Plasma FN concentrations were significantly different between the hypertensive group (52.9+/-14.5 mg/dl) and the normal blood pressure group (41.4+/-11.8 mg/dl) among the patients with ischemic heart disease (P<0.001). Plasma FN concentration was positively correlated with total cholesterol, triglyceride, systolic blood pressure and body mass index. In conclusion, the plasma fibronectin level may have pathogenetic implications in association with lipid components and blood pressure in patients with ischemic heart disease.     

Intracerebroventricular administration of atrial natriuretic peptide prevents increase of plasma ADH, aldosterone and corticosterone levels in restrained conscious dehydrated rabbits

In order to investigate the effects of centrally administered ANP on plasma ADH, aldosterone and corticosterone levels as well as on blood pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used. Measurements were made on restrained conscious animals one week after the implantation of an indwelling intracerebroventricular (icv) cannula and two indwelling intravascular catheters (intracarotid and intrajugular). Animals were classified into two main groups, those with water available ad libitum ("euhydrated" group) and those who were dehydrated for 24 h ("dehydrated" group) before blood pressure and heart rate recordings and blood sampling for hormonal determination. Each group's individuals were divided into two subgroups of five animals each. Blood samples were collected at 0 min (control) and 30, 60, 90, 120 min following icv administration of 25 microl of either artificial cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microg) in aCSF (25 microl) (subgroups "hANP"). Blood pressure and heart rate were also recorded at the same times. Plasma ADH, aldosterone and corticosterone concentrations were determined using RIA. The results were analysed by analysis of variance (ANOVA). Blood pressure and heart rate values were unaffected by water deprivation or by ANP administration. Mean plasma corticosterone levels at all times (30-120 min) were significantly higher (p<0.001) than those at 0 min time. Plasma corticosterone levels in the "dehydrated+aCSF" group were significantly higher (p<0.05) than in each of the other groups ("dehydrated+hANP", "euhydrated+aCSF", "euhydrated+hANP"). Plasma corticosterone levels in each of those other groups did not differ significantly from one another. Dehydration resulted in a tendency to increase in aldosterone levels (p<0.07), and icv administration of hANP tended (p<0.08) to prevent in the "dehydrated+hANP" experimental group the increase in aldosterone levels observed in the control "dehydrated+aCSF" group from 30 to 120 min. Dehydration resulted in an increase in ADH levels (p<0.0001), and icv administration of hANP prevented (p<0.05) in "dehydrated+hANP" experimental group the increase in ADH levels observed in the control "dehydrated+aCSF" group from 90 to 120 min. The increase of corticosterone and ADH and the tendency towards increase in aldosterone in the control dehydrated groups could possibly be due to the combined stress stimulus of dehydration and restriction in the restrain box. These results indicate that centrally administered ANP, at the concentration achieved in the present study, neither affects blood pressure and heart rate in conscious restrained euhydrated and 24 h-dehydrated NZW rabbits nor decreases the ADH, aldosterone and corticosterone response to dehydration, but does apparently modulate ADH, aldosterone and corticosterone responses to other stimuli in the dehydrated state. In conclusion, the results of this study confirm that brain ANP may have an inhibitory effect on stimulated ADH, aldosterone and corticosterone release.     

Relationship between dopamine release into hypophysial portal blood and prolactin release after morphine treatment in rats

To address the issue of whether, after morphine treatment, the reduced release of dopamine (DA) into portal blood is entirely responsible for the increased prolactin (PRL) release, the following study was conducted. The concentration of DA in plasma from a single portal vessel of untreated, ovariectomized rats was 1.85 +/- 0.33 ng/ml (mean +/- SE). Treatment of ovariectomized rats with alpha-methyl-p-tyrosine (alpha MT) caused a 91% reduction in the concentration of DA in portal plasma. Infusion of DA (0.4 microgram/min/kg BW) into a jugular vein of rats pretreated with alpha MT restored the DA concentration in portal plasma to that seen in untreated rats. Injection of morphine sulfate elicited a marked increase in the concentration of PRL in plasma. Infusion of DA at rates of 0.4 and 0.8 microgram/min/kg BW suppressed by 52 and 75%, respectively, the secretion of PRL after morphine treatment. Infusion of DA had no effect on the release of PRL induced by intracerebroventricularly administered beta-endorphin. Although treatment of rats with alpha MT caused release of PRL that was similar to that seen in rats treated with morphine, infusions of DA at 0.4 and 0.8 microgram/min/kg BW into alpha MT-treated, ovariectomized rats suppressed the secretion of PRL by 89 and 96%, respectively. Thus, after morphine treatment, the decreased release of DA into portal blood is not in itself sufficient to account for the increase seen in the secretion of PRL. It is suggested that morphine and opiate-like peptides induce the release of a hypothalamic substance(s) that stimulates PRL release.     

Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis

BACKGROUND: Lanreotide, a new long-acting somatostatin analogue, has been shown to inhibit the meal-stimulated increase of splanchnic blood flow in healthy volunteers. To date, similar data in patients with liver cirrhosis have not been available. We have examined the effect of lanreotide compared with placebo on meal-stimulated portal blood flow in patients with liver cirrhosis using Doppler ultrasound. METHODS: 20 cirrhotic patients (placebo n = 12, lanreotide n = 8) with proven portal hypertension were studied after an overnight fast. Lanreotide, at a dose of 100 microg/h, was infused intravenously over 7 h after a 1-hour basal period. In parallel to the intravenous infusion, a liquid test meal (Ensure plus, 1.5 kcal/min) was perfused for 7 h through an intraduodenal tube at a rate of 3 ml/min. Blood pressure, heart rate and portal vein blood flow (PVF, ml/min, Doppler technique) were determined at regular intervals. RESULTS: Baseline PVF amounted to 725 +/- 182 ml/min in the placebo and to 917 +/- 252 ml/min in the lanreotide group (n.s.). The meal-stimulated increase in PVF was blunted by lanreotide (AUC, % x min): 62,709.6 +/- 6,817 (placebo) vs. 45,237 +/- 2,507 (lanreotide), p < 0.05. Lanreotide also blunted the postprandial increase in heart rate for the first 2 h of meal perfusion. CONCLUSIONS: Because of potent inhibition of postprandial splanchnic hyperemia in patients with liver cirrhosis, lanreotide may be useful in the treatment of complications of portal hypertension.     

Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors

AIM： To characterize the correlation between severity of hepatopulmonary syndrome （HPS） and degree of hepatic dysfunction, and to explore how intestinal endotoxemia （IETM） affects the development of HPS in cirrhotic rats.
METHODS： Male Wister rats were fed with a diet containing maize flour, lard, cholesterol, and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide （NO） production inhibitor, N^ω-nitro-L-arginine methyl ester （L-NAME） intraperitoneally, and an iNOS inhibitor, aminoguanidine hydrochloride （AG） via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk, or a HO-1 inhibitor, zinc protoporphyrin （ZnPP） intraperitoneally 12 h prior to killing. Blood, liver and lung tissues were sampled.
RESULTS： Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1 ± 1.1 （count/filed） at the 4th wk to 14.5 ± 2.4 （count/filed） at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide （LPS） （0.31 ± 0.08 EU/mL vs control 0.09 ± 0.03 EU/mL）, alanine transferase （ALT, 219.1 ± 17.4 U/L vs control 5.9 ± 2.2 U/L） and portal vein pressure. Compared with normal control animals, the number of total cells in bronchoalveolar lavage fluid （BALF） of the cirrhotic rats at the 8th wk was not changed, but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold, protein expression of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） started to increase significantly at the 4th wk, and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS. NO2^-/NO3^- was also increased, which was cor     

Portal hemodynamics during nitroglycerin administration in cirrhotic patients

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 +/- 6.5 mm Hg (mean +/- S.D.) to 15.1 +/- 5.1 mm Hg (p less than 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 +/- 10 mm Hg to a peak decrease of 76 +/- 18 mmHg (p less than 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p less than 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 +/- 15 to 83 +/- 15 beats per min, p less than 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.     

Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists do not alter endogenous GnRH secretion in short-term castrated rams

The administration of GnRH agonists and antagonists suppresses pituitary LH secretion. However little is known about their effects on endogenous GnRH secretion. To determine if GnRH analogs act on GnRH secretion through a short or ultrashort loop feedback mechanism, experiments were performed to analyze GnRH secretion in hypophyseal portal blood of conscious short-term castrated rams under both agonist or antagonist treatment. In Study 1, six rams were castrated and surgically prepared for portal blood collection on day -7. Portal and peripheral blood were collected simultaneously every 10 min for 14-15 h on day 0. Five hours after the beginning of the portal blood collection, animals were injected im with 5 mg potent GnRH antagonist (Nal-Glu). In Study 2, six rams were treated daily from day -11 to day 0 with the GnRH agonist D-Trp6 GnRH (0.5 mg im). Castration and surgical preparation for portal blood collection were performed on day -7. On day 0 portal and peripheral blood were collected simultaneously every 10 min for 10-11 h. In both studies, to determine whether an increase in GnRH concentration in hypophyseal portal blood can overcome the inhibitory effect of the GnRH analogs, between 5 and 5.5 h after the injection of the analogs, endogenous GnRH secretion was stimulated by Naloxone administration (3 x 100 mg, iv, at 30-min intervals) followed by a bolus of exogenous GnRH (2 x 10 micrograms, iv at 30-min intervals). In Study 1, Nal-Glu administration led to a rapid cessation of pulsatile LH secretion for the duration of blood collection while GnRH pulse frequency and amplitude were not affected. GnRH and LH pulse frequency before and after Nal-Glu administration were, 6.2 +/- 0.6 vs. 5.7 +/- 0.8 (NS) and 5.3 +/- 0.3 vs. 0.3 +/- 0.2 pulses/6 h (P less than 0.001) respectively. In Study 2, peripheral LH secretion was completely suppressed while GnRH secretion (portal blood) remained pulsatile. GnRH pulses frequency and pulse amplitude were 4.3 +/- 0.3 pulses/6 h and 43.0 +/- 4.7 pg/ml, respectively. In both experiments, neither stimulation of endogenous GnRH secretion by naloxone nor administration of exogenous GnRH allowed reinitiation of LH secretion. However, additional studies in two animals of each treatment group (study-III) showed that this was clearly a dose related effect in antagonist treated but not in agonist-treated animals since higher doses of exogenous GnRH (i.e. 100 micrograms or 1000 micrograms) can increase significantly LH levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Increased levels of basic fibroblast growth factor are found in the cross-clamped heart during cardiopulmonary bypass

BACKGROUND: High concentrations of fibroblast growth factors (FGFs) are found in the heart. Even higher levels are measured during ischemia. Exogenous administration of FGF to ischemic myocardium promotes synthesis of collateral coronary circulation and induces local myocardial hypertrophy. The kinetics and the contribution of the heart and lungs to circulating basic FGF (bFGF) levels during cardiac surgery were characterized. PATIENTS AND METHODS: Plasma bFGF levels were measured in seven adults undergoing coronary artery bypass operations and 11 neonates undergoing congenital cardiac anomaly repair during cardiopulmonary bypass. RESULTS: In both the adult and the neonatal groups, bFGF plasma levels increased significantly immediately after removal of the aortic cross-clamp (adult group 15.43+/-6.3 aorta cross-clamped versus 29+/-4.1 after release, P=0.011; neonatal group 17.09+/-9.43 aorta cross-clamped versus 43.55+/-14.25 after release, P=0.004) and declined thereafter. In the adult group, higher levels of bFGF were recorded in blood recovered from the coronary sinus than in the aortic root during aortic cross-clamping (63.14+/-14.42 versus 43.86+/-12.05, P=0.011), and in both, levels were significantly higher than the peripheral measurements. CONCLUSIONS: Plasma bFGF levels increase during cardiopulmonary bypass. The source of this elevation is the lungs and heart.     

Invasive assessment of bacterial endotoxin and inflammatory cytokines in patients with acute heart failure

AIMS: To test the hypothesis that during acute heart failure endotoxin might be increased in hepatic veins as a sign of bacterial or endotoxin translocation from the bowel into the blood stream. METHODS AND RESULTS: In patients with acute heart failure (NYHA IV; n=17) levels of endotoxin, soluble (s) CD14, tumor necrosis factor alpha (TNFalpha and interleukin 6 (IL6)) were measured in blood drawn from an antecubital vein on admission and compared with age-matched patients with stable chronic heart failure (n=21) and healthy volunteers (n=9). All levels were systemically elevated during acute heart failure (all P<0.05); once patients were stable enough to undergo cardiac catheterization, endotoxin was found to be significantly higher in hepatic veins (0.62+/-0.05 EU/ml) than left ventricles (0.46+/-0.04 EU/ml; P<0.05), whereas sCD14, TNFalpha and IL6 were not different between these sites. At follow-up (29+/-6 days) endotoxin but not sCD14, TNFalpha or IL-6 was significantly lower as compared to baseline (P<0.05). CONCLUSIONS: Higher levels of endotoxin in hepatic veins as compared to the left ventricle during acute heart failure are suggestive of bacterial or endotoxin translocation from the bowel into the blood stream. This may lead to new treatment strategies. The lack of difference in TNFalpha levels between the pulmonary artery and the left ventricle sheds doubt on the heart as a source of systemically elevated TNFalpha levels.