Biomedical subjects

Yotaro Shinozawa

Publications and source records attributed to Yotaro Shinozawa.

7 recordsLinked to original sources

PubMed2005

Dynamic changes in expression of heme oxygenases in mouse heart and liver during hypoxia.

Heme oxygenase cleaves heme to form biliverdin, carbon monoxide (CO), and iron, and consists of two structurally related isozymes, HO-1 and HO-2. HO-2 is also known as a potential oxygen sensor. Here we show that the relative CO content in arterial blood, which reflects the total amount of endogenous heme degradation, dynamically changes in mice during acclimatization to normobaric hypoxia (10% O2), with the two peaks at 1 day and 21 days of hypoxia. The expression levels of HO-1 and HO-2 proteins were decreased by 20% and 40%, respectively, in the mouse liver at 7 days of hypoxia, which returned to the basal levels at 14 days. On the other hand, HO-1 and HO-2 proteins were increased 2-fold and 1.3-fold, respectively, in the heart at 28 days of hypoxia. Thus, hypoxia induces or represses the expression of HO-1 and HO-2 in vivo, depending on cellular microenvironments.

Animals↗

PubMed2005

[Fluid management and care for multiple organ dysfunction syndrome in patients with extensive burns].

Burn shock and multiple organ dysfunction syndrome (MODS) are the main causes of death in patients with extensive burns, and thus fluid management and care for MODS are crucial in the treatment of these patients. Several fluid formulas have been developed, although there is still controversy over the best formula. The important point is to understand how to deal with the different side effects inevitable with each fluid therapy: fluid restriction and/or diuretic administration in the refilling phase in fluid therapy with crystalloid, care for hypernatremia and/or a hyperosmolar state in fluid therapy with hypertonic lactated solution (HLS), etc. Precise fluid management is needed for aged patients, patients with extensive inhalation injury, extensive electric injury, and myocardial dysfunction, or patients in whom the start of fluid treatment was delayed. MODS in extensively burned patients is attributed to overwhelming burn stress and complicated sepsis, including bacterial translocation (BT). A dysfunctioning organ impairs another organ (organ interrelationships), and therefore substitution and/or recovery of a dysfunctioning organ are crucial. Debridement of skin with third-degree burns, suppression of BT, sanitary airway management, avoidance of unnecessary stress, and mediator modulation to stop the mediator cascade inducing MODS are also crucial.

Bacterial Translocation↗

PubMed2004

Correlation of glomerular permeability, endothelial injury, and postoperative multiple organ dysfunction.

PURPOSE: To determine whether the degree of microalbuminuria correlates with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction in patients who undergo emergency surgery. METHODS: We measured the urinary albumin : creatinine ratio (ACR) within 24 h after surgery in 31 patients and examined its relationship with various clinical measurements. RESULTS: The ACR increased during the first 24 h postoperatively. The log ACR correlated with the serum thrombomodulin concentration measured on the same day, but not with the level of plasma von Willebrand factor antigen. The increase in the log ACR correlated with the acute physiology and chronic health evaluation score (APACHE III), the simplified acute physiology score, the multiple organ dysfunction score, and the score of sequential organ failure assessment (SOFA) calculated on the same day, and the blood volume lost during the operation. The log ACR did not correlate with the white blood cell count or the serum C-reactive protein measured at the same time. The log ACR correlated with SOFA on postoperative days 3, 7, and 10, and mortality increased in accordance with the increase in log ACR. CONCLUSIONS: The urinary ACR correlated with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction.

APACHE↗

PubMed2004

[Correlation between intravascular coagulation/fibrinolysis system and cytokines].

Bacterial factors stimulate the release of tissue factor as well as proinflammatory and antiinflammatory cytokines. TNF augments inflammation, TNF and IFN-gamma induce coagulation, and IL-1beta induces coagulation and fibrinolysis. IL-8 augments synergistic inflammation and coagulation. IL-6 augments coagulation and inhibits fibrinolysis. IL-10 inhibits inflammatory process and inhibits fibrinolysis. IL-4, IL-13, and TGF-beta act for anticoagulation. Administration of IL-2, G-CSF or IFN-gamma has been reported to have side effect of induction of coagulation. IL-12 induces coagulation first and fibrinolysis later. On the other, tissue factor induces proinflammatory (except TNF) and antiinflammatory cytokines, and thrombin enhances inflammation. Patients who died of SIRS/sepsis have been complicated with hypercoagulopathy and impaired fibrinolysis correlated with increased IL-10 production. Inhibition of IL-10 production or administration of fiblynolitic agents may be useful. Recently, activated protein C (APC) which has antiinflammatory effect has been paid attention in the treatment of SIRS/sepsis.

Aged↗

PubMed2003

[Animal models for sepsis].

When new immunomodulatory agents are developed for the treatment of sepsis, the efficacy is usually tested in animal models before going to clinical trials. However, despite promising preclinical evidence, dozens of new agents have failed to demonstrate clinical efficacy. One of the reasons may be that the preclinical trials were conducted using animal models that did not adequately reflect clinical realities. Various kinds of experiments utilized for the development of new agents were carried where bolus or short term continuous infusions of large doses of bacteria or endotoxin were administered intravenously. Massive i.v. bolus models using bacteria or endotoxin generally produce a rapid hypodynamic cardiovascular response with the animals dying within hours. The serum cytokine response is transient and is much greater in magnitude than that observed in septic patients. For the preclinical testing of agents, 1) i.v. bacteria and endotoxin models in which the total challenge dose of adequate bacteria or endotoxin is reduced and/or the length of administration time is increased, and 2) peritonitis models, e.g., cecal ligation and puncture and peritoneal implantation of bacteria or endotoxin, will become reasonable choices. The animals are also required to receive volume resuscitation and adjuvant antibiotic therapy.

Animals↗

PubMed2003

[Pathophysiologies of ischemic/reperfusion injuries associating with hemorrhagic shock and up-to-date treatment].

During the ischemic state, hypoxanthine and xanthine oxidase are accumulated in the ischemic cells, and thereafter when oxygen is reperfused into ischemic cells, hypoxanthine and xanthine oxidase work to change oxygen into oxygen radicals. Oxygen radicals themselves damage various cells and they also injure cells by activating the transcription factors of inflammatory cells to induce special protein synthesis depending on individual cells. These processes are considered to be related to the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS). Hemorrhagic shock is a generalized ischemic state and intestinal ischemia is more profound and more severely damaging than in other vital organs because of luxurious flow to the latter organs. The lack of microcirculation in large areas of the intestinal mucosa and in high-density areas of intestinal immune cells results in the synthesis of various inflammatory mediators, in the appearance of adhesion molecules, in the induction of tissue factors, and finally in the development of impairment of remote vital organs and MODS when oxygen is reperfused. There is no therapy for reperfusion injury after a prolonged ischemic state, and thus it is most important to reduce the intestinal ischemic time by supplying sufficient oxygen to preserve intestinal circulation and to commence early enteral nutrition. The development of new treatments to interrupt the vicious pathological cascade inducing MODS after ischemic reperfusion injury is mandatory.

Humans↗

PubMed2002

Recombinant human interleukin-1alpha increases serum albumin, Gc-globulin, and alpha1-antitrypsin levels in burned mice.

The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distant target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase proteins, that carries out specific immunoprotective functions. In this study we investigated the effects of daily recombinant human interleukin-1alpha (rhIL-1alpha) administration on the serum levels of negatively regulated, i.e., albumin and Gc-globulin and positively regulated, i.e., alpha1-antitrypsin, acute phase proteins in a murine model of thermal injury. Adult CF-1 female mice underwent a 6.5-seconds, 20% total burn surface area, full thickness steam injury, and received either intraperitoneal rhIL-1alpha (20 microg x kg(-1) x day(-1)) or diluent for 10 days. Seven and 14 days after injury, mice were sacrificed, and serum albumin, Gc-globulin and alpha1-antitrypsin levels were measured by crossed immunoelectrophoresis technique. Thermal injury significantly lowered serum albumin levels, tended to decrease Gc-globulin levels, and increased serum alpha1-antitrypsin levels. Daily rhIL-1alpha administration after burn injury prevented hypoalbuminemia, and increased serum levels of Gc-globulin and alpha1-antitrypsin. IL-1 therapy might be helpful to maintain the homeostasis and immunity of the host after thermal injury.

Animals↗