Nobuaki Matsuo

THE ROLE OF INTRAPULMONARY NITRIC OXIDE GENERATION IN THE DEVELOPMENT OF ADULT RESPIRATORY DISTRESS SYNDROME

This study was conducted to investigate the role of nitric oxide (NO) in the development of adult respiratory distress syndrome (ARDS). An experimental model of endotoxemia-induced ARDS was prepared in guinea pigs and the following parameters were measured: pulmonary vascular permeability, the nitrate and nitrite concentrations in blood and bronchoalveolar lavage fluid (BALF), and the activities of constitutive and inducible NO synthase in lung tissue following the administration of lipopolysaccharide (LPS). Following the intravenous administration of 0.5mg/kg LPS, the pulmonary vascular permeability increased, as did the concentrations of nitrate and nitrite in the BALF and blood. The activities of both constitutive and inducible NO synthase (NOS) increased significantly in the lung tissue 4h after the intravenous administration of LPS, the constitutive form showing significantly higher activity than the inducible form. Furthermore, the increase of vascular permeability in the lungs after LPS injection was blocked by the subcutaneous administration of NG-monomethyl-l-arginine. These observations indicate that the intrapulmonary generation of NO may play an important role in the development of ARDS.

Changes in brain ECF amino acids in rats with experimentally induced hyperammonemia.

Using microdialysis, we studied brain extracellular fluid (ECF) amino acid metabolism in rats with experimentally induced hyperammonemia and regional elevation of brain ECF ammonia levels. The total brain ECF amino acid level was increased by an elevation of the blood ammonia level. Hyperammonemia elevated brain ECF aromatic amino acids and reduced arterial blood branched chain amino acids. When rats with hyperammonemia were intravenously administered norleucine, the brain ECF norleucine level rose markedly, suggesting increased permeability of the blood-brain barrier. When rats with hyperammonemia were infused with a branched chain amino acid-rich preparation, the elevated brain ECF aromatic amino acids level was not suppressed. Following local intracerebral ammonia infusion, only glutamate levels showed a marked elevation. These results suggest that impairment of the blood-brain barrier related to hyperammonemia increases the inflow of low molecular weight substances including amino acids. Furthermore, the ammonia-induced increase of glutamate in the cerebral ECF suggests that high ammonia levels may increase the excitability of the brain. Thus, ammonia may serve as a key factor in the onset of hepatic encephalopathy.

Hyperammonemia inhibits platelet aggregation in rats.

The effect of hyperammonemia on ex vivo platelet function and in vivo nitric oxide synthesis was evaluated in rats. In addition, mitochondrial energy production was assessed from the fluorescence intensity of tetramethylrhodamine ethyl ester (TMRE). Continuous ammonium acetate infusion significantly reduced ex vivo platelet aggregation concomitant with a decrease of the platelet cytoplasmic ATP level. The serum level of L-arginine, as well as the levels of nitrite and nitrate (oxidative by-products of nitric oxide), increased with ammonium infusion. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, did not affect the ammonia-induced rise in L-arginine, but substantially attenuated the associated decrease of platelet ATP and TMRE fluorescence as well as diminishing the anti-aggregatory effect of ammonia infusion. These findings suggest that the synthesis of nitric oxide from L-arginine is accelerated by continuous ammonium infusion and inhibits ex vivo platelet aggregation in the rat, probably by reducing mitochondrial energy production.

Adrenal myelolipoma: A case report and review of the literature

A case of a 73 year old man who was preoperatively diagnosed as possibly having adrenal myelolipoma is presented herein. Adrenal myelolipoma is an uncommon benign tumor of which only 74 foreign cases and 43 Japanese cases have been previously reported in the literature dealing with surgically removed myelolipomas. The most consistent complaint of the adrenal myelolipoma sufferer is abdominal pain, caused by hemorrhaging in the tumor, and many cases are associated with obesity, hypertension and/or diabetes mellitus. There is now an increasing number of such cases being diagnosed during abdominal scanning with ultrasonography or computerized tomography for unrelated problems, whereupon the myelolipoma is usually surgically resected. With the availability of modern scanning techniques and fine needle biopsy, however, it should be possible to adopt a more conservative approach to the management of asymptomatic adrenal myelolipoma. Nevertheless, symptomatic or large tumors, must be removed since there is a high risk of spontaneous hemorrhage.

Determination of overt carnitine palmitoyltransferase by reversed-phase high-performance liquid chromatography

A method for the determination of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.19) in isolated rat liver mitochondria by reversed-phase high-performance liquid chromatography is described. Enzyme activity is assayed by direct determination of coenzyme A (CoA) released from palmitoyl-CoA within 60 min by a linear gradient system. CPT 1 in rat liver mitochondria can be assayed from only 30 micrograms of mitochondrial protein per millilitre of assay mixture. The changes in the kinetic parameters of CPT I, including Ki for malonyl-CoA, resulting from the fasting-feeding cycle are also discussed.

Accelerated hepatic lipid synthesis in fasted septic rats.

We examined changes in the enzyme activities and metabolites related to hepatic fatty acid synthesis in fasted rats with sepsis produced by cecal ligation and puncture. Sepsis stimulated the in vivo incorporation of tritiated water into hepatic fatty acids and nonsaponifiable lipids. The activities of acetyl-CoA carboxylase, ATP-citrate lyase, and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and malic enzyme), the tissue levels of citrate and malonyl-CoA, and the dephosphorylation of carboxylase were increased in the livers of fasted septic rats compared with fasted sham-operated control rats. These results indicate that sepsis stimulated hepatic lipogenesis and sterologenesis in fasting rats. Furthermore, sepsis reduced the specific activity of hepatic mitochondrial carnitine palmitoyltransferase and raised that of glycerophosphate acyltransferase, suggesting an increased diversion of cytosolic acyl-CoA towards esterification. These intrahepatic metabolic changes strongly suggest that sepsis causes anabolic action on hepatic lipid metabolism.