Hiroshi Kasahara

The effect of a nucleotide-nucleoside solution on hepatic regeneration after partial hepatectomy in rats

After hepatectomy, purine and pyrimidine metabolism is a key process in the synthesis of DNA and RNA and maintaining cellular energy metabolism. The purpose of this study is to evaluate changes in blood purine and pyrimidine levels after partial hepatectomy and the effect of purine and pyrimidine nucleoside solution injection on hepatic regeneration under the hypothesis that the rat after partial hepatectomy requires substrates for salvage nucleotide synthesis and changes blood nucleoside and nucleobase levels. Blood levels of nucleotides, nucleosides, and nucleobase by high-performance liquid chromatography method and liver ATP level by enzymatic analysis, and the effect of preoperative injection of nucleoside solution (OG-VI) on hepatic regeneration ratio and hepatocytes DNA synthesis, were assessed in rats after 70% partial hepatectomy. Decreased liver adenosine triphosphate and increased plasma xanthine and hypoxanthine after partial hepatectomy indicated an increase in catabolism of purine nucleotides in regenerating liver. Plasma thymidine and cytidine levels increased, then returned to the prevalue, suggesting that the thymidine and cytidine pool was enlarged. OG-VI increased labeling indices of hepatocytes at postoperative d 1 (POD) and hepatic regeneration ratio at POD 14. Blood purine nucleobase and pyrimidine nucleoside levels change after partial hepatectomy and preoperative supply of nucleoside solution is effective for increasing hepatocytes DNA synthesis and hepatic regeneration after partial hepatectomy.

Effect of a parenteral nucleoside-nucleotide mixture on hepatic metabolism in partially hepatectomized cirrhotic rats

After hepatectomy, purine and pyrimidine metabolism is a key process in synthesis of DNA and RNA and in energy metabolism. To supply nucleosides for salvage synthesis, nucleoside-nucleotide mixture solutions have been developed, and they have been found to improve protein metabolism and hepatic regeneration after partial hepatectomy in normal rats. However, the effect of the solution in cirrhotic liver, common in patients with hepatocellular carcinoma, has not been reported. The aim of this study was to evaluate the metabolic effect of the nucleoside-nucleotide mixture on cirrhotic rats after partial hepatectomy. Seventy percent partial hepatectomy was performed in thioacetamide-administered cirrhotic rats. The fractional protein synthetic rate, nitrogen balance, hepatic content of nucleic acid, and blood chemistry after the administration of the nucleoside-nucleotide mixture solution (OG-VI) with total parenteral nutrition was evaluated at 7 d after partial hepatectomy. OG-VI increased hepatic RNA level and hepatic fractional protein synthetic rate (p < 0.05). It is concluded that the nucleoside-nucleotide mixture solution is an effective nutritional supplement to the metabolism of cirrhotic rats after partial hepatectomy.

The effect of partial hepatectomy on blood purine levels in rats and patients.

Purine metabolism is a key metabolic process after partial hepatectomy in the synthesis of DNA and RNA, and in the energy metabolism for hepatic regeneration1. However it is not evaluated in clinical situations due to the difficulty in measuring changes of purine levels in the liver itself. In order to get a basic understanding of purine metabolism in clinical hepatectomy cases, blood samples are used for analysis in this study. Also, the liver is the main nondietary source of purines in mammalian cells2 and changes in blood level may affect purine metabolism in various tissues.

The Effect of Dietary Nucleic Acid Deficiency and the Administration of a Nucleotide and Nucleosides Mixture Solution on Endotoxin Shock in Rats

The importance of dietary nucleic acid in modulation of immune function without disease has been reported in nutritional disorder except under surgical stress. Dietary nucleic acid deficiency decreases T lymphocytes function1 and dietary ribonucleic acid (RNA) enhances immune response2. However, it is not known whether dietary nucleic acid influences on macrophage function. Recently, monocytes/macrophages are considered as key factors in the pathogenesis of systemic inflammatory response leading to septic shock by producing humoral mediators under endotoxin stimulation3, 4. Therefore, the aim of this study is to evaluate the influence of dietary nucleic acid deficiency on endotoxin shock and macrophage functions stimulated with lipopolysaccharide (LPS), which is the major component of endotoxin. Then, the effect of intraperitoneal administration of a nucleotide and nucleosides mixture solution (OG-VI)5 was evaluated.

A Nucleotide and Nucleosides Mixture Solution Improves Recovery of Energy Metabolism after Hepatic Ischemia in Rats

Hepatic ischemia/reperfusion is a common problem encountered under many clinical conditions, and it occurs in a variety of surgical procedures. Possible consequences include liver failure and/or multi-organ system failure, both of which have high rates of morbidity and mortality.1,2 Efforts to minimize the extent of injury incurred during the ischemic period or to maximize reparative process following ischemia have importance for survival.3 In vivo 31P-nuclear magnetic resonance (NMR) spectroscopy has been used to follow the response of hepatic high-energy phosphates during hepatic ischemia/reperfusion.4 It measures the continuous changes of hepatic adenosine triphosphate (ATP) levels and their metabolites, and is an effective tool to evaluate the serial data in the individual following drug treatment.

A Case Report of Choledochocele (type III choledochal cyst of the Alonso‐Lej classification)

Abstract: The case of a 33‐year‐old woman with a rare type of choledochal cyst (Choledochocele; Alonso‐Lejs type III) is described. The patient had undergone prior cholecystectomy. Hypotonic duodenography showed a smooth defect in the duodenum. Endoscopic retrograde cholangiopancreato‐graphy (ERCP) showed a cystic dilatation of the terminal portion of the common bile duct. Endoscopic ultrasonography (EUS) showed a cystic lesion at the same site. This case was preoperatively diagnosed by ERCP and EUS. Transduodenal sphincteroplasty was done and good results were obtained.

Utilization of purine and pyrimidine in human gastric cancer cells (KATO III): effect of a nucleotide and nucleosides mixture (OG-VI) solution on proliferation with coadministration of 5-fluorouracil.

Purine and pyrimidine are essential for cellular proliferation1, 2, 3. But, purine and pyrimidine are synthesized from glutamine in de novo synthesis pathway and cultured cancer cells do not require them in the medium. This is the reason that utilization of nucleosides by human cancer cells and their changes with 5 fluorouracil (5FU), the fluorinated analogue of uracil which is used in chemotherapy for various tumors2, 3, has not been reported. In this study, as a source of purine and pyrimidine, a solution containing a mixture of nucleosides and a nucleotide (OG-VI), developed recently as a nutritional supplement4, was used in the medium. It consists of purines, guanosine 5’-mono-phosphate (5’-GMP) and inosine, and pyrimidines, cytidine, uridine, and thymidine (TdR). It is known to increases hepatic regeneration and improve protein metabolism after partial hepatectomy in rats5, 6, and increase DNA synthesis in primary cultured hepatocytes7.