Muscle hematoma: a critically important complication of alcoholic liver cirrhosis.

An iliopsoas hematoma can occur either spontaneously or secondary to trauma or bleeding tendency due to hemophilia and anticoagulant therapy. Although liver cirrhosis is commonly associated with coagulopathy, iliopsoas hematoma is very rare. We herein, present a case of bilateral iliopsoas hematoma in a patient with alcoholic cirrhosis, and review the literature on muscle hematoma associated with cirrhosis. A 56-year-old man with alcoholic cirrhosis was admitted in a state of shock with anemia. The cause of anemia could not be detected, and the patient was treated conservatively. The site of bleeding was not detected with either gastroduodenal endoscopy or upper abdominal computed tomography, the latter of which did not include the iliopsoas muscle. He died on the 10th day of admission and bilateral iliopsoas hematomas were found on autopsy. An iron stain was positive in the iliopsoas muscle. Eight cases of muscle hematoma associated with cirrhosis, including the present case, were found in a review of the literature. Four of these cases involved the rectus abdominis muscle, 3 involved the iliopsoas muscle and 1 involved combined muscles. Alcoholic cirrhosis accounted for 75% of the cases. One case (12.5%) was associated with virus-related cirrhosis, and another with combined virus- and alcohol-related cirrhosis. The mortality rate was 75% despite early diagnosis and low risk scores for cirrhosis. Muscle hematoma in patients with cirrhosis is closely related to alcoholism, and the mortality rate of the condition is extremely high. In conclusion, muscle hematoma should be recognized as an important complication of cirrhosis.

Effect of fasting on PPARgamma and AMPK activity in adipocytes.

We investigated the effects of fasting on gene expression and intracellular signals regulating energy metabolism in adipose tissue. Following fasting for 15h or 39h, epididymal fat pads were isolated from Wistar rats. PPARgamma mRNA levels decreased in the adipose tissues isolated from rats fasted for 39h, whereas adipocyte lipid-binding protein (aP2) and lipoprotein lipase (LPL) mRNA levels increased. Overnight fasting increased the AMP/ATP ratio and AMP-activated protein kinase (AMPK) in adipose tissue, but not in muscle or liver tissue. In addition, the effect of 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) on PPARgamma expression in primary cultured adipocytes was investigated. AICAR reduced PPARgamma mRNA levels but increased aP2 and LPL mRNA levels. Thus, fasting-induced AMPK activation may affect on the regulation of gene expression in adipocytes.

Effect of dehydroepiandrosterone on insulin sensitivity in Otsuka Long-Evans Tokushima-fatty rats.

In order to clarify the effect of dehydroepiandrosterone (DHEA) on improvement of insulin resistance, we examined the effects of overexpression of wild-type protein kinase C-zeta (wt-PKCzeta)/3-phosphoinositide-dependent protein kinase-1 (wt-PDK1) and kinase-inactive PKCzeta/PDK1 (DeltaPKCzeta/DeltaPDK1) on DHEA-induced [(3)H]2-deoxyglucose (DOG) uptake using the electroporation method in rat adipocytes. Overexpression of wt-PKCzeta and wt-PDK1 significantly increased in DHEA-induced [(3)H]2-DOG uptake. Wortmannin completely suppressed DHEA-induced [(3)H]2-DOG uptake in wt-PKCzeta- and wt-PDK1-transfected adipocytes. Overexpression of neither DeltaPKCzeta nor DeltaPDK1 increased DHEA-induced [(3)H]2-DOG uptake. Otsuka Long-Evans fatty rats (OLETF), animal models of type 2 diabetes, and Long-Evans Tokushima rats (LETO) as control, were treated with 0.4% DHEA for 2 weeks. Insulin-induced [(3)H]2-DOG uptakes, activations of PI 3-kinase and PKCzeta of adipocytes were significantly increased in DHEA-treated OLETF rats. Moreover, plasma glucose levels in OLETF rats after treatment with DHEA for 2 weeks were significantly lower than treatment without DHEA, but not in LETO rats. These results indicate that DHEA treatment may improve glucose tolerance through a PI 3-kinase-PKCzeta pathway and downregulates adiposity in OLETF rats.

Platelet aggregation in obese and diabetic subjects: association with leptin level.

To clarify the relationship between serum leptin concentration and platelet aggregation mechanism, we investigated serum leptin concentration and agonist-induced platelet aggregation in eight obese subjects and eight non-obese and non-diabetic controls. In addition we also measured them in 15 type 2 diabetic subjects and 17 control subjects. Maximum platelets aggregation rate (MPAR) in control and diabetic subjects by adenosine diphosphate (ADP), collagen and thrombin were measured by aggregometer after pretreatment with 100 ng/ml leptin for 60 min. The MPAR by 0.15 U/ml thrombin stimulation in leptin-treated platelet in the controls was significantly increased compared with that in non-treated platelets, but not by ADP and collagen stimulation. Despite a significantly higher concentration of leptin in obese subjects, agonist-induced platelet aggregation in obese subjects was not different from that in controls. There were no significant differences in serum leptin concentration and MPAR by various agonists between diabetic and control subjects. When MPAR by ADP in the diabetic subjects was divided into two groups (high group: >50%, low group: <50%), the serum leptin concentration in the high group was significantly increased, compared with that in the low group. These results suggest that ADP-induced platelet aggregation may be associated with serum leptin concentration in diabetic subjects, and that leptin-associated platelet aggregation may affect the development of cardiovascular complications in obese and diabetic subjects.

TNFalpha reduces the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) via the production of ceramide and activation of atypical PKC.

Although tumor necrosis factor alpha (TNFalpha) decreases the expression of peroxisome proliferator-activated receptor gamma (PPARgamma), its mechanism is not understood. We evaluated the effect of ceramide, the second messenger of TNFalpha, on the expression of PPARgamma in primary cultured adipocytes. PPARgamma mRNA and aP2 mRNA levels were measured with real-time PCR. The PPARgamma protein level was measured with immunoblot. C6- and C2-ceramide, but not dihydroC6-ceramide, reduced the expression of PPARgamma in a time and concentration dependent manner. The application of 1 microM C6-ceramide for 36 h reduced PPARgamma mRNA level, aP2 mRNA level, and PPARgamma protein level to 56.3%, 80.4% and 62.1%, respectively. Since ceramide is known to activate atypical PKC, we also studied the role of atypical PKC on the PPARgamma reducing effect. Overexpression of wild type PKCzeta magnified and accelerated the effect of TNFalpha and C6-ceramide on PPARgamma mRNA levels, whereas overexpression of dominant negative PKCzeta abolished the effect. We also found that the overexpression of constitutive active PKCzeta reduced PPARgamma mRNA level, aP2 mRNA level, and PPARgamma protein level to 61.4%, 70.3% and 81.6%, respectively. Furthermore, TNFalpha activated nuclear factor-kappaB (NF-kappaB), known as a downstream effector of PKCzeta to 256.6%, which was enhanced with overexpression of wild-type PKCzeta. On the other hand, treatment with phorbol 12-myristate 13-acetate, another activator of NF-kappaB, also reduced the expression of PPARgamma to 57.8%. These results indicate that the reducing effect of TNFalpha is mediated through ceramide, atypical PKC and NF-kappaB pathway.

[Effect of gamma-aminobutyric acid-rich germinated brown rice on indexes of life-style related diseases].

We examined the effects of gamma-aminobutyric acid-rich germinated brown rice (germinated brown rice) on principal indexes of life-style related diseases in 67 volunteers aged 71 +/- 8. They were divided into two groups; germinated brown rice group, which had an equal amount of the germinated brown rice to polished rice for 11 to 13 months, and control group, which had polished rice alone for the same period. Differences of indexes before and after the examination between the two groups were compared. Significant increases in body fat ratio, hemoglobin A1c and mean red cell volume and a significant decrease in mean red cell hemoglobin concentration were observed in the germinated brown rice group. However, there was no difference of changes in body mass index, blood pressure, serum lipid, hepatic and renal functions, bone metabolic markers, bone density, depression score, red blood cell counts, hemoglobin, hematocrit, and homeostasis model assessment of insulin resistance between the two groups. These findings suggested that germinated brown rice might not improve glucose metabolism.