Macrophage inflammatory protein-2 induced by TNF-alpha plays a pivotal role in concanavalin A-induced liver injury in mice.

Elsevier , Nakamura, K; Okada, M; Yoneda, M; Takamoto, S; Nakade, Y; Tamori, K; Aso, K; Makino, I, JOURNAL OF HEPATOLOGY, 35(2), 2001, 217-224. authorBackground/Aims: Macrophage inflammatory protein-2 (MIP-2), one of CXC chemokines is involved in the recruitment of neutrophils in several tissue injury. In this study, we investigated a role of MIP-2 in concanavalin A (Con A)-induced liver injury in mice. Methods:Liver injury was induced by intravenous injection of Con A (15 mg/kg) and plasma alanine aminotransferase (ALT), MIP-2 levels were determined and histological assessment of the liver was performed. Anti-mouse MIP-2 antibody was intravenously administered 30 min before Con A injection. Results: Plasma ALT level significantly elevated and reached a maximum at 8 h after Con A injection. Plasma MIP-2 level was also elevated and reached peak value at 2 h after Con A injection. The elevated ALT level by Con A injection was significantly inhibited by MIP-2 antibody. The elevated plasma MIP-2 level after Con A injection was significantly reduced by TNF-a antibody, and MIP-2 was induced in plasma after recombinant TNF-a injection. Hepatic necrosis and infiltration of neutrophils were observed after Con A injection, and these histological changes were attenuated by MIP-2 antibody. Conclusion: These findings suggest that Con A induces TNF-a release, and this TNF-a stimulates MIP-2 induction, at least partially contributing to the liver injury mediated through the recruitment of neutrophils

Relationship of a Special Acidified Milk Protein Drink with Cognitive Performance: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Young Adults

A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida–Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchida–Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior

Antithrombin III prevents concanavalin A-induced liver injury through inhibition of macrophage inflammatory protein-2 release and production of prostacyclin in mice.

Elsevier , Nakamura, K. ; Ito, T. ; Yoneda, M. ; Takamoto, S. ; Nakade, Y. ; Okamoto, S. ; Okada, M. ; Yokohama, S. ; Aso, K. ; Makino, I., JOURNAL OF HEPATOLOGY, 36(6), 2002, 766-773. authorBackground/Aims: Recently, we have reported that macrophage inflammatory protein-2 (MIP-2) plays a pivotal role in concanavalin A (Con A)-induced liver injury. In this study, we investigated the effect of antithrombin III (AT-III) on liver damage, and production of MIP-2 and prostacyclin in this model. Methods: Liver injury was induced by intravenous injection of Con A (15 mg/kg) and AT-III was administered (50, 250 and 500 units/kg, iv) 30 min before Con A injection. Plasma levels of alanine aminotransferase (ALT), MIP-2 and 6-keto-prostaglandin F1a (6k-PG-F1a), stable metabolite of prostaglandin I2 (prostacyclin), were determined. Results: The elevated plasma ALT levels 8, 16, 24 h after Con A injection were inhibited by AT-III pretreatment. The elevated plasma MIP-2 levels were significantly inhibited by AT-III pretreatment compared with vehicle treatment. The inhibitory effect of AT-III on plasma ALT and MIP-2 in Con A-induced liver injury was attenuated by indomethacin (5 mg/kg, ip). Plasma concentration of 6k-PG-F1a at 2 h after AT-III injection was significantly elevated compared with baseline and vehicle pretreatment. Conclusion: These findings suggest that AT-III prevents Con A-induced liver injury through an inhibition of MIP-2 release and a production of prostacyclin

Accurate diagnosis and treatment of Vibrio vulnificus infection: a retrospective study of 12 cases

BACKGROUND AND AIMS: Vibrio vulnificus causes an infectious disease that has extremely poor convalescence and leads to necrotic fasciitis. In this study, we sought to define the characteristic epidemiology of V. vulnificus infection and clarify its diagnosis at the global level. METHODS: Over a period of 10 years, we investigated the appearance of symptoms, underlying conditions, treatment, and mortality in 12 patients (eight men, four women; >50 years old; average age, 66 years,) infected with V. vulnificus. RESULTS: The development of symptoms occurred primarily between June and September, a period during which seawater temperature rises and the prevalence of V. vulnificus increases. All patients had underlying diseases, and seven patients reported a history of consuming fresh fish and uncooked shellfish. The patients developed sepsis and fever with sharp pain in the limbs. Limb abnormalities were observed on visual examination. All patients underwent debridement; however, in the survival group, the involved limb was amputated early in 80% patients. The mortality rate was 58.3%. CONCLUSION: Recognition of the characteristic epidemiology and clinical features of this disease is important, and positive debridement should be performed on suspicion. When the illness reaches an advanced stage, however, amputation should be the immediate treatment of choice