Ablation of cardiac TIGAR preserves myocardial energetics and cardiac function in the pressure overload heart failure model.

Despite the advances in medical therapy, the morbidity and mortality of heart failure (HF) remain unacceptably high. HF results from reduced metabolism-contraction coupling efficiency, so the modulation of cardiac metabolism may be an effective strategy for therapeutic interventions. Tumor suppressor p53 (TP53) and its downstream target TP53-induced glycolysis and apoptosis regulator (TIGAR) are known to modulate cardiac metabolism and cell fate.

First-in-Man Clinical Pilot Study Showing the Safety and Efficacy of Intramuscular Injection of Basic Fibroblast Growth Factor With Atelocollagen Solution for Critical Limb Ischemia.

Background: Therapeutic angiogenesis with basic fibroblast growth factor (bFGF) with atelocollagen was confirmed in a study using a limb ischemia mouse model. Because the number of elderly patients with critical limb ischemia (CLI) is increasing, particularly that caused by arteriosclerosis obliterans (ASO), the development of less invasive angiogenesis therapies desired.

Methods and results: This first-in-man clinical study was designed to assess the safety and efficacy of i.

Cardiac-Specific Bdh1 Overexpression Ameliorates Oxidative Stress and Cardiac Remodeling in Pressure Overload-Induced Heart Failure.

Background: Energy starvation and the shift of energy substrate from fatty acids to glucose is the hallmark of metabolic remodeling during heart failure progression. However, ketone body metabolism in the failing heart has not been fully investigated.

Methods And Results: Microarray data analysis and mitochondrial isobaric tags for relative and absolute quantification proteomics revealed that the expression of D-β-hydroxybutyrate dehydrogenase I (Bdh1), an enzyme that catalyzes the NAD/NADH coupled interconversion of acetoacetate and β-hydroxybutyrate, was increased 2.

-Glutamate is metabolized in the heart mitochondria.

-Amino acids are enantiomers of L-amino acids and have recently been recognized as biomarkers and bioactive substances in mammals, including humans. In the present study, we investigated functions of the novel mammalian mitochondrial protein 9030617O03Rik and showed decreased expression under conditions of heart failure. Genomic sequence analyses showed partial homology with a bacterial aspartate/glutamate/hydantoin racemase.

Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure.

Failing heart loses its metabolic flexibility, relying increasingly on glucose as its preferential substrate and decreasing fatty acid oxidation (FAO). Peroxisome proliferator-activated receptor α (PPAR-α) is a key regulator of this substrate shift. However, its role during heart failure is complex and remains unclear.

Diabetes-Related Ankyrin Repeat Protein (DARP/Ankrd23) Modifies Glucose Homeostasis by Modulating AMPK Activity in Skeletal Muscle.

Skeletal muscle is the major site for glucose disposal, the impairment of which closely associates with the glucose intolerance in diabetic patients. Diabetes-related ankyrin repeat protein (DARP/Ankrd23) is a member of muscle ankyrin repeat proteins, whose expression is enhanced in the skeletal muscle under diabetic conditions; however, its role in energy metabolism remains poorly understood. Here we report a novel role of DARP in the regulation of glucose homeostasis through modulating AMP-activated protein kinase (AMPK) activity.

Pyk2 aggravates hypoxia-induced pulmonary hypertension by activating HIF-1α.

Pulmonary arterial hypertension (PAH) is a refractory disease characterized by uncontrolled vascular remodeling and elevated pulmonary arterial pressure. Although synthetic inhibitors of some tyrosine kinases have been used to treat PAH, their therapeutic efficacies and safeties remain controversial. Thus, the establishment of novel therapeutic targets based on the molecular pathogenesis underlying PAH is a clinically urgent issue.

Loss of apoptosis regulator through modulating IAP expression (ARIA) protects blood vessels from atherosclerosis.

Atherosclerosis is the primary cause for cardiovascular disease. Here we identified a novel mechanism underlying atherosclerosis, which is provided by ARIA (apoptosis regulator through modulating IAP expression), the transmembrane protein that we recently identified. ARIA is expressed in macrophages present in human atherosclerotic plaque as well as in mouse peritoneal macrophages.

Aging differentially alters the expression of angiogenic genes in a tissue-dependent manner.

Organ functions are altered and impaired during aging, thereby resulting in increased morbidity of age-related diseases such as Alzheimer's disease, diabetes, and heart failure in the elderly. Angiogenesis plays a crucial role in the maintenance of tissue homeostasis, and aging is known to reduce the angiogenic capacity in many tissues. Here, we report the differential effects of aging on the expression of angiogenic factors in different tissues, representing a potentially causes for age-related metabolic disorders.

A case of hepatic pseudolymphoma observed without surgical intervention.

We report a case of liver pseudolymphoma that has been followed up without surgical resection after the diagnosis. A 63-year-old woman with a hepatic hypo-echoic lesion, 16mm in diameter was referred to our hospital. Laboratory data on admission were within normal limits.

Long-term outcomes for patients with solitary hepatocellular carcinoma treated by laparoscopic microwave coagulation.

Background: Although many reports on the treatment of hepatocellular carcinoma (HCC) by microwave coagulation have been published recently, none have incorporated data for the long-term therapeutic efficacy of laparoscopic microwave coagulation (LMC). In the current study, the efficacy of LMC was assessed.

Methods: The authors performed LMC under local anesthesia in 69 previously untreated patients with solitary HCCs < or = 4.

Laparoscopic radiofrequency ablation of hepatocellular carcinoma in the caudate lobe by using a new laparoscopic US probe with a forward-viewing convex-array transducer.

Background: The use of a new end-fire type laparoscopic US probe with a forward-viewing convex-array transducer allows the caudate lobe of the liver to be accessed. This study evaluated the preliminary results of treatment of hepatocellular carcinoma in the caudate lobe by using this new instrument.

Methods: Three patients with hepatocellular carcinoma in the caudate lobe were selected.

First stable 7,7,8,8-tetraaryl-o-quinodimethane: isolation, X-ray structure, electrochromic response of 9,10-bis(dianisylmethylene)-9,10-dihydrophenanthrene.

Oxidative cyclization of 2,2'-bis(dianisylethenyl)biphenyl yielded the dicationic salt of phenanthrene-9,10-diylbis(dianisylmethylium), which in turn afforded the severely congested title molecule as the first stable tetraaryl-o-quinodimethane derivative upon reduction.

Infection of a Japanese patient by genotype 4 hepatitis e virus while traveling in Vietnam.

Cases of imported hepatitis E in industrialized countries infected with a genotype 1 hepatitis E virus (HEV) have been identified. We report a 56-year-old Japanese man who acquired infection with a genotype 4 HEV with 98.8% identity to a Vietnamese isolate after ingestion of uncooked shellfish while traveling in Vietnam.

Sporadic acute hepatitis E of a 47-year-old man whose pet cat was positive for antibody to hepatitis E virus.

We encountered a patient with sporadic acute hepatitis E who had not traveled to areas endemic for hepatitis E virus (HEV) infection and may have been infected in Japan. The patient was a 47-year-old male who had no history of blood transfusion or contact with travelers to hepatitis E-endemic regions or unspecified individuals. The disease presented with general malaise, fever, and brown urine as chief complaints in April 2002.