Volume 105  ·   Issue 08  ·  1992

The changes in the cellular concentrations of ATP, ADP, AMP and oxidative phosphorylation of mitochondria in the liver were investigated experimentally in rats with acute pancreatitis (AP). The energy charge (ATP + 1/2ADP)/(ATP+ ADP+ AMP) of the liver decreased from 0.866 to 0.806 (P<0.05) at 24 hours after onset of AP, and continuously decreased to 0.769 (P<0.01) at 48 hours. On the other hand, the mitochondrial phosphorylative activity increased rapidly to 130% and 157% in the controls at 12 hours and 24 hours respectively and then decreased rapidly at 48 hours. The blood ketone body ratios were paralleled to the hepatic energy charge level in AP rats. These findings suggest that the nature of the derangement of the hepatic energy metabolism initiated by AP is that the effects of mitochondria damage result in a significant decrease in liver energy charge level, leading ultimately to hepatocellular impairment, and the measurement of the blood ketone body ratio is useful in evaluating the energy status of the liver in AP patients.

The authors previously reported the successful reversal of lethal D-Gal induced hepatic necrosis in rats by human hepatic stimulator substance (hHSS), a liver specific growth factor partially purified from human fetal liver cells, which promoted hepatocyte proliferation. In this study, they further investigated the mechanism of hHSS in improving survival of experimental acute hepatic failure. Our results demonstrated that the level of alanine transaminase and endotoxin in the plasma and lipid peroxides in the liver of chemically poisoned rats were reduced by hHSS to different extent at different periods of observation compared with the saline control group. The apparent recovery of liver function and the increase of 3H-TdR incorporation into hepatic DNA correlated with the morphologic changes observed under light and electron microscopes, showing that the damages inflicted on the cellular and subcellular structure in the liver of hHSS-treated rats were greatly alleviated and rapidly repaired. Therefore, hHSS, which can prevent liver deterioration and promote hepatocyte regeneration, may be a new hepatic stimulator factor readily available for clinical use.

The effect of heparin on the anionic sites of glomerular basement membrane (GBM) in adriamycin-induced nephrotic rats was studied by means of calculating the polyethyleneimine (PEI) stained particles under electron microscope. The results showed that treatment with heparin under the anticoagulant effect markedly reduced the loss of anionic sites within lamina rara externa (LRE) of GBM and also the urinary protein excretion in nephrotic rats. The results demonstrated that one of the mechanisms of heparin in preventing the structural damage of glomeruli in kidney diseases was the reduction of the loss of anionic sites within LRE, indicating that changes in biomembrane charge played an important role in the pathogenesis of nephrotic syndrome. The results provided a scientific basis for the use of heparin to treat glomerular diseases.

The effects of anisodamine on acetylcholine-induced endothelium-dependent relaxation were studied in organ chambers and under bioassay conditions. In organ chamber experiments, both acetylcholine and bradykinin induced an endothelium-dependent relaxation of norepinephrine-contracted canine femoral arteries in a concentration-dependent manner; the relaxation induced by acetylcholine, but not that by bradykinin, was inhibited by anisodamine or atropine in a concentration-dependent manner. In bioassay experiments, a denuded ring of left circumflex coronary artery was superfused with perfusate passed through segment of femoral artery with endothelium or a direct superfusion line. Acetylcholine induced the release of relaxing factor(s) from the segment with endothelium causing a relaxation of bioassay ring and the relaxation was eliminated by anisodamine infused into the perfusion line above, but not below, the perfused segment. The results suggest that anisodamine, like atropine, is able to inhibit acetylcholine-induced endothelium-dependent relaxation by blocking endothelial muscarinic receptors which activate the release of endothelium-derived relaxing factor(s).

Twenty-three cases of spinal extradural tumors were differentiated with CT myelography. In 16 benign tumors, the proximal and/or distal widened extradural space was filled with adipose tissue, whereas in 7 malignant tumors, the widened extradural space showed soft-tissue density. This difference is helpful in evaluating the nature of the tumors.

Four strains of enterovirus and 1 strain of adenovirus were isolated from stool and pharyngeal swabs by inoculation into primary human embryonic kidney cell culture in 25 cases of dorsum manus infantile papular dermatitis. Two strains of Coxsackie A-9 virus and 1 strain of Echovirus-25 were identified. With the isolated virus as antigen, a matched pair study by sera antibody test was carried out in 43 children with papular dermatitis and 40 normal individuals as controls. In 26 cases of Coxsackie A-9 virus positive papular dermatitis, a 4-fold rise (>1:1.6) in the relative serum antibody was observed in 80.77%, while no high levels were observed in patients with Echovirus-25 and adenovirus dermatitis (<1:16). The authors can reasonably conclude that epidemic Coxsackie A-9 virus infection is obviously related to infantile papular dermatitis and is probably the main cause of the disease.

A series of 108 geriatric patients with ischemic cerebrovascular disease were treated with low dose aspirin (acetylsalicylic acid, ASA). Daily doses of 100 mg, 50 mg and 25 mg were administered to three groups of 36 patients. Changes in platelet aggregation responses were dynamically observed in 64 (22 normal subjects, 42 patients). Monitoring of 22 normal subjects revealed inhibition of platelet aggregation at a dose of 300 mg or 100 mg which could last as long as 7 days. This suggests that 100 mg or less could be clinically effective. Satisfactory inhibitory effects on platelet aggregation were observed in all three groups, with 14 patients in each group given daily doses of 100 mg, 50 mg and 25 mg during four weeks' observation. The most effective inhibition was obtained in the 50 mg group. Therefore, the authors recommend 50 mg/d as the optimal dosage for low dose aspirin therapy in geriatric patients.

An inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), was used to deplete the endogenous thiols in mammalian cells in vitro. In this study, the cytotoxicity of BSO and BSO combined with the hypoxic cell radiosensitizer misonidazole (MISO) was investigated. Both aerobic and hypoxic cytotoxicity of MISO was found to be increased. The concentration of BSO required to reduce the colony forming ability to 50% (Cc) for the chronic cytotoxicity on V79 cells was 0.03 mmol/L under aerobic condition, while the Cc for the acute cytotoxicity on V79 cells under hypoxic and aerobic conditions was 0.4 and 0.5 mmol/L. The growth inhibition rate of human tumor cells K562 and SGC-7901 by BSO was 6.89-26.06% and 12.01-55.69%, respectively. Enhanced cytotoxicity activity was observed when BSO was used in combination with cis-dichlorodiamino Pt(II) or 5-fluorouracil.

In order to explore the substantial role of monoconjugated bilirubin (MCB) in gallstone formation, bile pigment precipitation and hemolytic jaundice, three experimental protocols have been studied, namely, (1) MCB and dietary induced pigment gallstone model, (2) MCB in human gallstone and incubated bile precipitates and (3) MCB in hemolytic jaundice. It was found that doubly increased MCB accounted for 1/3 of the total pigment in lithogenic guinea pig and CDCA plus glycine possessed certain protective effect from gallstone development; MCB was found in human gallstones both in bilirubinate and cholesterol type, and an unknown pigment, possibly an isomer of MCB, was found in black stone. During experimental hemolytic jaundice model preparation, both MCB and UCB were elevated, and MCB was found increased by 10 times, even exceeding the concentration of DCB when the injected bilirubin was about 4 mg/kg of body weight. It is reasonable to consider that MCB as a coprecipitant with UCB and a precursor of UCB played an essential role in the pathogenesis of gallstones.

Resection of the extrahepatic bile tract for hilar bile duct carcinoma was performed at the PLA General Hospital, with a resectability rate of 62% (31/50) and no operative mortality. Hepatic lobectomy was performed at the same time in 16 cases (51.6%). Reoperative resections were successfully done in 5 cases; 4 cases are still living 1-4 years after the second operation. The cause of late death was mainly biliary infection due to local recurrence and bile duct obstruction. The median survival period was 15 months. 32 cases were studied pathologically, of which 27 were resected surgical specimens and 5 autopsies. The tumors were histologically classified into 4 types: papillary adenocarcinoma (6 cases); well differentiated adenocarcinoma (21); poorly differentiated adenocarcinoma (3); and simple carcinoma (2). The importance of early diagnosis of hilar bile duct carcinoma at its subclinical stage before appearance of clinical jaundice is stressed.