Reduced contractility and histological changes in the gallbladder due to portal hypertension in a hamster cirrhosis model

BACKGROUND/AIMS: Little is known about the relationship of portal venous pressure to contractility and histological changes in the gallbladder. In this study, we investigated the relationship between portal hypertension and contractility and histological changes in the gallbladder in a hamster cirrhosis model. METHODS: Liver cirrhosis was induced in the hamsters (n = 20) by thioacetamide (TAA). Portal venous pressure was directly measured using a pressure-measuring instrument. The contractility of the gallbladder was appraised by the diameter before and after caerulein treatment. Gallbladder wall thickness and vessel areas in tissues were evaluated in relation to the portal venous pressure. RESULTS: The portal venous pressure, gallbladder wall thickness with submucosal edema and area of vessels in the gallbladder wall in the cirrhosis group were significantly increased compared with those in the control group (n = 20, receiving saline instead of TAA). The gallbladder contraction rate in the cirrhosis group was significantly decreased compared with that in the control group. In the cirrhosis group, there were positive correlations between the portal venous pressure and the gallbladder contraction rate, gallbladder wall thickness, and area of vessels. CONCLUSIONS: In the gallbladders of experimental cirrhotic hamsters, portal hypertension caused dilatation of the vessels as well as submucosal edema, and was an important factor in the increased thickness and reduced contractility of the gallbladder wall.     

99mTc-MIBI used for diagnosis of portal hypertension: an experimental study

The authors investigated the relationship between portal-systemic shunting and portal pressure in 16 CCl4-induced cirrhotic wistar rats by 99mTc-MIBI photography of heart and liver. Based on radio-counts taken at 30 minutes after 99mTc-MIBI was given per rectum 8 rats or medial clonic vein 8 rats, heart radio-counts/liver radio-counts (H/L) and portal-systemic shunting index (SI) were recorded. It was shown that 1. H/L and SI of the two cirrhotic groups were greater than those of normals (P < 0.001); 2. H/L in cirrhotic rats by rectum 99mTc-MIBI administration was more closely related to free portal pressure (FPP, r = 0.83, P < 0.01) than in those by venous route (r = 0.74, P < 0.05) and its regressive formation FPP (kPa) = 0. 24 + 4.06 (H/L) was deduced and used to calculate portal pressure of cirrhotic rats. The very good relationship between the calculated and measured portal venous pressure was shown in a group of 12 cirrhotic rats (r = 0.85, P < 0.01). These findings suggested that the rectum administration of 99mTc-MIBI may be a useful method in calculating portal pressure and portal-systemic shunting in portal hypertensive patients.     

Prostacyclin production in acute, chronic, and long-term experimental portal hypertension

Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, is a yellow-orange dye derived from the rhizome of the plant Curcuma longa. Curcumin has demonstrated phototoxicity to several species of bacteria under aerobic conditions (Dahl, T. A., et al., 1989, Arch. Microbiol. 151 183), denoting photodynamic inactivation. We have now found that curcumin is also phototoxic to mammalian cells, using a rat basophilic leukemia cell model, and that this phototoxicity again requires the presence of oxygen. The spectral and photochemical properties of curcumin vary with environment, resulting in the potential for multiple or alternate pathways for the exertion of photodynamic effects. For example, curcumin photogenerates singlet oxygen and reduced forms of molecular oxygen under several conditions relevant to cellular environments. In addition, we detected carbon-centered radicals, which may lead to oxidation products (see accompanying paper). Such products may be important reactants in curcumin's phototoxicity since singlet oxygen and reduced oxygen species alone could not explain the biological results, such as the relatively long lifetime (t1/2 = 27 s) of the toxicant responsible for decreased cell viability.     

Doppler sonography and hepatic vein catheterization in portal hypertension: assessment of agreement in evaluating severity and response to treatment

The authors analyzed the role of individual differences in age, gender, and 16-year declines in reasoning and vocabulary as predictors of 16-year changes in text and list recall and recognition in 82 adults aged 55-81 years at baseline. Declines in reasoning as well as being older at baseline predicted declines in text recall. Male gender and declining in vocabulary predicted declines in list recall. There were no reliable predictors of declines in recognition. The findings suggest that changes in abilities, as well as age and gender, predict declines on memory tasks. However, the specific predictors varied across tasks.     

Adrenoceptors in the hepatic tissues in cirrhotic rats and cirrhotic patients with portal hypertension]

Phalangeal dislocations of toes are extremely rare in childhood and usually can be treated by closed reduction. We present a proximal interphalangeal dislocation of the fourth toe with an irreducible avulsion fracture of the middle phalanx requiring open reduction. To our knowledge concomitant avulsion fractures in this condition have not been reported thus far in pediatric patients. The pathological mechanism of this injury is discussed, and the significance of the plantar plate for joint stability is emphasized.     

Haemodynamic changes in portal hypertension: new insights in the pathogenesis and clinical implications

In man and experimental animals, portal hypertension with portal-venous collaterals, is associated with a hyperdynamic circulation, caused by peripheral vasodilatation, mainly in the splanchnic bed. This peripheral vasodilatation is clinically important, since it is thought to be responsible for the pathogenesis of complications of portal hypertension such as ascites, the hepatorenal syndrome and portal hypertensive gastropathy and colopathy. Many cirrhotic patients may not die primarily because of their hepatic dysfunction, but rather because of the consequences of the circulatory abnormalities which are secondary to the liver disease. Circulating hormonal vasodilators from intestinal origin such as glucagon, insufficiently cleared by the liver, are only partly responsible for these changes. Recent experimental data point to a role for an increased production of the locally acting potent vasodilator nitric oxide in the vascular wall, in the pathogenesis of the hyperdynamic circulation. Furthermore, nitric oxide seems to play an important role in the development of portal-venous collaterals. Modulation of the nitric oxide production might offer therapeutic options for the treatment of portal hypertension and its complications.     

Increase of hematocrit in experimental renal hypertension and its reversal

The electroencephalograms of 82 infants (between 27 and 37 weeks of conceptional age) recorded during the neonatal period were analyzed and compared with the ultimate clinical evolution. Three groups of infants were identified according to their neurological state at 3 years of age or older: group A: normal (34 infants), group B: minor neurological sequellae (13 infants) and group C: major neurological sequellae (17 infants). A fourth group (group D: 18 infants) died during the neonatal period. The E.E.Gs were classified as: normal, questionably abnormal, moderately abnormal or grossly abnormal. The analysis revealed that E.E.Gs classified as grossly abnormal, were found only in groups B, C and D. Serial E.E.Gs were of more value in distinguishing these groups. Only infants in groups C and D (with I exceptional case in group B) had E.E.Gs which remained abnormal for several weeks or which deteriorated during the neonatal period. This study shows the prognostic value of the E.E.G. recorded during the neonatal period, particularly serial recordings obtained during and after a period of clinical deterioration. A detailed statistical analysis of the E.E.Gs is in progress.     

Renal metabolic changes relating to calculogenesis in an experimental model of calcium containing renal stone formation in rabbits

In histochemical studies it was shown that sulfated acid glycosaminoglycans (AGAGS) were produced and secreted into the tubular lumen in renal papilla, but not in the renal cortex of muddy stone forming kidney. There was no secretion of sulfated AGAGS in renal papilla histochemically during hydronephrosis before stone formation. On autoradiographic study with the use of 45Ca and 35S for labeling of sulfated AGAGS, we found that 45Ca accumulated in renal papilla of muddy stone forming kidney, but not in the other. 35S apparently accumulated into muddy stones. Measurement of calcium content of the renal papilla and cortex proved the results of autoradiographic studies, and measurement of uronic acid in the urine showed increased secretion of AGAGS in the urine from muddy stone forming kidney. From these results it was proposed that the sulfate AGAGS secreted in the urine could bind calcium crystals to each other amd make crystals aggregate massively.     

The abnormal hepatic scan of chronic liver disease: its relationship to hepatic hemodynamics and colloid extraction

To help explain the characteristic hepatic scan pattern of chronic liver disease, the degree of scan abnormality (scan score, SS) after administration of technetium-99m sulfur colloid (Tc) was compared with data obtained at hepatic vein catheterization in 28 patients. Although SS showed a correlation with wedged hepatic vein pressure (r = +0.491), the scan abnormality was not directly due to portal hypertension because it remained unchanged when the latter was relieved by portacaval shunt. Also, the scan abnormality was found to be unrelated to a low hepatic blood flow. Scan abnormality was not attributable primarily to hyperactivity of the reticuloendothelial (RE) cells of the spleen and bone marrow since fractional clearance (K) of Tc from the blood was decreased rather than increased in patients with abnormal scans. SS was inversely correlated with K or Tc (r = -0.575) and with hepatic extraction efficiency for Tc (r = -0.673), showing that the basic abnormality was poor extraction of the colloid by the RE cells of the liver with a resultant increase in the amount available for extrahepatic localization. Indirect evidence suggests that this poor extraction of colloid is due to intrahepatic shunts bypassing hepatic RE cells.     

Age- and gender-related changes in the hepatic metabolism of 2-methylpropene and relationship to epoxide metabolizing enzymes

The effect of age and gender on the in vitro biotransformation of 2-methylpropene, an alkene metabolized to 2-methyl-1,2-epoxypropane, was studied. The epoxide concentration and the epoxide metabolizing enzymatic activities were investigated in male and female Brown Norway rats of different ages. Liver tissue of senescent rats was exposed to smaller 2-methyl-1,2-epoxypropane concentrations than that of young animals, although changes during ageing were rather modest. With advancing age a feminization of male glutathione S-transferase and cytosolic epoxide hydrolase activities was found, as well as a significant decline of the female microsomal epoxide hydrolase activity and an increase of the cytochrome P-450 content in the oldest female rats.     

Acetabular changes in an experimental model of developmental dysplasia of the hip (DDH)

We wished to correlate the morphological acetabular changes in developmental dysplasia of the hip (DDH) with changes at the tissue level. A secondary aim was to develop a way of measuring the dysplastic acetabulum. We studied the changes in rabbit acetabula after maintaining knee extension, measuring the major diameter from the acetabular notch to the farthest opposite point on the acetabular margin. The minor diameter was at right angles to this. The dysplastic acetabula showed elongation along the major diameter compared to control hips. Microscopic sections were made along major and minor diameters. The posterosuperior lip of the dysplastic acetabulum showed an early eversion of the acetabular cartilage. Growth of the articular cartilage in this new direction accounted for the acetabular elongation. As well as providing insight into the manner of acetabular shape change, the findings suggest the nature of remodeling required before normal acetabular growth can resume during treatment.     

The postprandial portal flow is related to the severity of portal hypertension and liver cirrhosis

BACKGROUND/AIMS: Diminished postprandial portal hyperemia has been demonstrated by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic role is unclear. This prospective study was therefore undertaken in patients with varying severity of portal hypertension and degree of liver cirrhosis. METHODS: Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Hemodynamic parameters were related to the degree of esophageal varices, variceal bleeding, portal hypertensive gastropathy and Child-Pugh score. RESULTS: The postprandial portal blood velocity increment was low in patients with esophageal varices of any degree (22-24%), compared to patients without varices (49%, p<0.01) and healthy controls (65%, p<0.001), but was not different in patients with or without variceal bleeding (22% vs. 20%). In contrast, the congestion index (CI; ratio of portal vein cross-sectional area and portal blood velocity) pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/-0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive gastropathy was not related to any of the portal flow parameters. The portal blood velocity increment was comparable in controls (65%) and patients with Child-Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease in congestion index in patients with the most severe cirrhosis (p<0.01 class C vs. class A and B). CONCLUSIONS: The postprandial rise in portal flow is inversely related to the severity of portal hypertension and liver cirrhosis, and may be a valuable parameter with respect to the risk of variceal bleeding.     

Lipid peroxidation and changes in T lymphocyte subsets and lymphocyte proliferative response in experimental iron overload

This study was undertaken to investigate the hypothesis that lipid peroxidation might be associated with immunological abnormalities in experimental hemosiderosis. The correlation between the degree of plasma and spleen lipid peroxidation with lymphocyte proliferative response and with the proportion of T lymphocyte subsets was studied in normal and iron overloaded male Sprague Dawley rats. The iron-loading protocol consisted of a total dose of iron-dextran (1.5 mg/Kg body weight) divided in daily i.m. injections over twenty consecutive days. Lipid peroxidation was measured by the thiobarbituric acid assay in plasma and in homogenates of spleen. Plasma lipid peroxide level increased rapidly after i.m. administration of iron-dextran and decreased sharply at 48 h after the last injection. Conversely, a progressive increase of lipid peroxidation in homogenates of spleen was observed in the course of the iron overload protocol, remaining high even at 50 days after initiation of iron-dextran injections. The increase of spleen lipid peroxide levels was associated with decreased lymphocyte proliferative response to Con A in iron overloaded rats. The addition of superoxide dismutase and catalase to lymphocyte cultures reversed the inhibition of the proliferative response, implicating reactive species of oxygen as the causative agents of these alterations. These effects may be related with the enhanced membrane and DNA damage occurring during intracellular and extracellular peroxidation. Negative correlations between helper/cytotoxic ratio and malondialdehyde levels were obtained in blood and spleen during iron administration. These results supports the hypothesis that lipid peroxidation plays a role in the immunological abnormalities observed in experimental hemosiderosis.     

Study of portal hypertension in children with special reference to sclerotherapy

Spinal cord injuries are rare in children, in face of their higher mobility comparing to adults. The high cervical and the thoracic segments of the spine are more frequently affected. In the last 10 years we had 90 cases of spinal injuries in our service being 12 with neurologic deficient (8 male and 4 female) and four of them without radiographic abnormality, even in the dynamics studies. The authors emphasise the possibility of occurrence of neurologic deficit in children after trauma, even without any radiographic abnormality.     

Changes of sex hormone levels in patients with hepatitis B virus-related postnecrotic cirrhosis: relationship to the severity of portal hypertension

The purpose of this study was to develop a model in which the regional pharmacokinetics of a drug in tumor and nontumorous tissue could be evaluated under a variety of physiological conditions. To this effect, the growth of a human choriocarcinoma cell line (JAR) was evaluated in pigs immunosuppressed with 25 mg cyclosporine/kg every 24 h. During an initial study, we demonstrated that suspensions containing approximately 3 million JAR cells with and without 1 million normal human fibroblasts injected s.c. into the inguinal region of pigs resulted in the growth of tumors consisting primarily of polygonal neoplastic cells. Multinucleate tumor cells, inflammatory cells, necrotic debris, and vascular endothelial cells were also present. Maximal tumor size was noted on day 12, after which time tumor regression occurred. The coinoculation of fibroblasts resulted in significantly larger tumors. Two single pedicle, axial pattern tubed flaps were created in the inguinal area of 4 pigs. JAR cells and fibroblasts were transplanted to one flap to allow for tumor formation. The other flap served as a nontumorous control. Both flaps were removed for perfusion with a physiological solution 11 days later. Glucose utilization, lactate concentrations, lactate dehydrogenase activities, and microscopic evaluation of skin samples were used to assess flap viability. All flaps remained viable for 8 h of perfusion. The only differences detected between nontumorous and tumor flaps was the initial perfusion pressure which was significantly lower in tumor flaps (P < 0.05). The isolated perfused tumor and skin flap is unique in that it consists of a tumor surrounded by normal tissue with an intact microvascular system and can be utilized to design regional pharmacokinetic studies describing drug distribution in tumor tissue.     

Hypogenesis of right hepatic lobe accompanied by portal hypertension: case report and review of 31 Japanese cases

We report a rare case of hypogenesis of the right lobe of the liver with portal hypertension and a review of 31 cases of agenesis or hypogenesis of the right hepatic lobe reported in Japan. A 74-year-old man consulted our hospital for further examination after a mass screening for gastric cancer. On physical examination liver enlargement was palpable, but liver function tests were normal. Abdominal ultrasonography, computed tomography, technetium-99m liver scintigraphy, and endoscopic retrograde cholangiopancreatography revealed a small right hepatic lobe and moderate splenomegaly, in contrast to a hypertrophic lateral segment of the left hepatic lobe, as well as ectopic dislocation of the gallbladder. Endoscopic examination revealed esophageal varices, indicating portal hypertension. Abdominal angiography demonstrated mild shunt flow between the hepatic artery feeding from the gastroduodenal artery and the portal vein. A biopsy specimen taken from both lobes of the liver showed normal liver tissue histologically. Based on these findings, we made a definite diagnosis of hypogenesis of the right lobe of the liver with portal hypertension. The present case appears to be the first such case accompanied by portal hypertension reported in Japan.     

Time course of changes in lactate and free fatty acids after experimental brain injury and relationship to morphologic damage

Regional levels of lactate and free fatty acids (FFA) were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min after injury, tissue concentrations of lactate were elevated in the cortices and hippocampi of both ipsilateral and contralateral hemispheres. Whereas lactate levels had returned to normal by about 20 min after injury in the penumbra and contralateral cortices, their elevation persisted in the ipsilateral injured cortex and hippocampus for 24 h after injury. Increases in the levels of FFA (particularly stearic and arachidonic acids) were observed in the cortices and hippocampi of both ipsilateral and contralateral hemispheres at 5 min after injury; these levels returned to normal in only the penumbra and contralateral cortices by 20 min after injury. Increased amounts of palmitic and oleic acids were also found only in the injured left cortex and ipsilateral hippocampus at 20 min or later after injury. In general, these elevations persisted for as long as 6 to 24 h in the injured cortex and for 2.5 to 24 h after injury in the ipsilateral hippocampus. Histologic studies revealed a similar extent of damage in the cortex between 5 min and 24 h after injury, whereas damage in the CA3 region of the ipsilateral hippocampus increased during that period. These findings suggest a role for lactic acid and FFA, two secondary injury factors, in neuronal cell loss after brain injury.