Role of ammonia in the pathogenesis of brain edema.

The role of hyperammonemia in the pathogenesis of cerebral edema was investigated using mongrel dogs to develop a treatment for cerebral edema in acute hepatic failure. Intravenous infusion of ammonium acetate alone into dogs did not induce brain edema, although blood ammonia reached unphysiologically high levels. However, ammonium acetate infusion during mannitol-induced reversible (osmotic) opening of the blood-brain barrier (BBB) effectively induced cytotoxic brain edema. Pretreatment with a branched-chain amino acid (BCAA; valine, leucine and isoleucine) solution prevented an increase in intracranial pressure (ICP) and brain water content, and caused a decrease in brain ammonia content and an increase in brain BCAA and glutamic acid. The results suggest that ammonia plays an important role in the pathogenesis of cerebral edema during acute hepatic failure and that BCAAs accelerate ammonia detoxification in the brain.</p

Elevation of Ammonia Contents in the Cerebral Hemisphere under the Blood-Brain Barrier Opening

Elevation of ammonia contents was observed 1 hr following infusion of 4% ammonium acetate only in the cerebral hemisphere where reversible opening of the blood-brain barrier was induced by intracarotid injection of 0.1% deoxycholic acid. This finding suggests that ammonia may contribute to hepatic encephalopathy, when the permeability of the blood-brain barrier is altered

Bile Acid and Ammonia-Induced Brain Edema in Rats

Infusion of bile acid such as chenodeoxycholic acid or deoxycholic acid through the carotid artery of rats produced reversible and unilateral opening of the blood-brain barrier without any tissue damage. Intravenous drip infusion of ammonium acetate during the opening resulted in severe edema of the brain. The results suggest the importance of bile acid and ammonia for the pathogenesis of brain edema frequently observed in acute hepatic failure

Two cases of breast carcinoma with osteoclastic giant cells: Are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer

A Case of Liposarcoma With Peritonitis Due to Jejunal Perforation

A 21-year-old man, who had been treated for congenital dilatation of the bile duct 13 years previously, presented with an acute abdomen. The physical examination suggested peritonitis, and an emergent laparotomy was performed. A perforation was foundin the jejunum approximately 100 cm distal to the ligament of Treitz, followed by resection of a 60-cm jejunal segment. No tumorous lesions were found during the operation, and the resected jejunal segment showed only focal myxomatous thickening of the serosa. Despite intensive therapy, he died of uncontrollable septic shock 2 days after the operation. Unexpectedly, however, histological examination revealed a liposarcoma, showing an unclassifiable histology. From the distribution of the lesion and the histological findings, it is thought that a primary lesion was somewhere else, covered by severe adhesions due to the previous operation, and that the tumor cells spreading from it could have caused the jejunal perforation through vascular involvement. Although extremely rare, liposarcomas in the abdomen can cause intestinal perforation. It is important for both clinicians andpathologists to carefully investigate the cause of an unusual clinical presentation such as intestinal perforation

Clinical significance of eosinophilia in the diagnosis of halothane-induced liver injury.

Three patients with severe halothane-induced liver injury are described. All patients received halothane anesthesia twice within a short period. High fever and jaundice were noticed soon after the second operation. The prothrombin time was less than 40%, and eosinophilia was greater than 7% prior to these symptoms. Other causes of liver injury were excluded. Diagnostic criteria for halothane-induced liver injury are proposed.</p

Cerebral edema associated with acute hepatic failure.

The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64%) of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more frequently in patients later found to have cerebral edema. Moreover, the length of time from deep coma to death was much shorter in the brain edema cases with cerebral herniation than without herniation.</p

Assay procedures for cathepsin B, H and L activities in rat tissue homogenates.

Cathepsin B, H and L activities in small amounts of rat tissue homogenates corresponding to 10 micrograms protein were determined with 7-amino-4-methyl-coumarin conjugates as substrates. A new procedure for serum cathepsin H activity was also developed. High cathepsin B and H activities were found in kidney, spleen and liver. Liver cathepsin B, H and L activities in D-galactosamine-injured rats were decreased concomitantly with an increase in serum cathepsin H activity.</p

Detection of type V collagen-degrading enzyme activity in human liver.

&lt;p&gt;Type V collagen-degrading enzyme activity was detected as a metalloprotease acting at neutral pH in the human liver. Type V collagen extracted from human placenta and labeled with [1-14C] acetic anhydride was used as the substrate in the assay. Four major degradation products with relatively high molecular weights were observed upon polyacrylamide gel electrophoresis of the incubation mixture of type V collagen and liver homogenate. The significance of the measurement of this enzyme activity was discussed in relation to the clarification of the mechanism of liver fibrosis.&lt;/p&gt;</p

Effect of continued drinking on prognosis of alcoholic liver cirrhosis.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.</p