Platelet-derived endothelial cell growth factor (PD-ECGF) is up-regulated in human hepatocellular carcinoma (HCC) and the corresponding hepatitis liver

BACKGROUND/AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is one of the angiogenic factors. The aim of this study was to examine the PD-ECGF concentrations in hepatocellular carcinoma, background liver, and normal liver tissues, and to elucidate their significance on clinicopathological outcomes. METHODOLOGY: The concentration of PD-ECGF in the tissue extract was determined by enzyme-linked immunosorbent assay. RESULTS: PD-ECGF concentrations were significantly higher in hepatocellular carcinoma and background liver tissues compared with normal control liver (p = 0.003, p = 0.001, respectively). PD-ECGF concentrations in hepatocellular carcinoma tissues were positively correlated with intratumoral arteriole densities (r = 0.667, p = 0.009), and were higher in less differentiated carcinomas (p = 0.039). However, tumor PD-ECGF concentration did not affect the patients' disease-free survival rates. Those in the background liver tissues were positively correlated with histological activity index scores (r = 0.650, p = 0.001) and serum alanine aminotransferase levels (r = 0.0452, p = 0.035). CONCLUSIONS: PD-ECGF is up-regulated in hepatocellular carcinoma and the corresponding hepatitis liver. The PD-ECGF concentrations in hepatocellular carcinoma correlated positively with microvessel density, lower differentiation, yet not with patients' prognosis. The concentrations of PD-ECGF in the corresponding hepatitis liver correlated positively with the degree of active hepatitis.     

Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency

Angiotensin II (Ang II) plays a pivotal role in cardiovascular remodeling leading to hypertension, myocardial infarction, and stroke. Pitavastatin, an HMG-CoA reductase inihibitor, is known to have pleiotropic actions against the development of cardiovascular remodeling. The objectives of this study were to clarify the beneficial effects as well as the mechanism of action of pitavastatin against Ang II-induced organ damage. C57BL6/J mice at 10 weeks of age were infused with Ang II for 2 weeks and were simultaneously administered pitavastatin or a vehicle. Pitavastatin treatment improved Ang II-induced left ventricular hypertrophy and diastolic dysfunction and attenuated enhancement of cardiac fibrosis, cardiomyocyte hypertrophy, coronary perivascular fibrosis, and medial thickening. Ang II-induced oxidative stress, cardiac TGFbeta-1 expression, and Smad 2/3 phosphorylation were all attenuated by pitavastatin treatment. Pitavastatin also reduced Ang II-induced cardiac remodeling and diastolic dysfunction in eNOS-/- mice as in wild-type mice. In eNOS-/- mice, the Ang II-induced cardiac oxidative stress and TGF-beta-Smad 2/3 signaling pathway were enhanced, and pitavastatin treatment attenuated the enhanced oxidative stress and the signaling pathway. Moreover, pitavastatin treatment reduced the high mortality rate and improved renal insufficiency in Ang II-treated eNOS-/- mice, with suppression of glomerular oxidative stress and TGF-beta-Smad 2/3 signaling pathway. In conclusion, pitavastatin exerts eNOS-independent protective actions against Ang II-induced cardiovascular remodeling and renal insufficiency through inhibition of the TGF-beta-Smad 2/3 signaling pathway by suppression of oxidative stress.     

Acute myeloid leukemia with t(8;21)(q22;q22) manifesting as granulocytic sarcomas in the rhinopharynx and external acoustic meatus at relapse after high-dose cytarabine: case report and review of the literature

We report a 31-year-old female with t(8;21)(q22;q22) acute myeloid leukemia (AML), M2 in the FAB classification. Complete remission was achieved with daunorubicin and cytarabine induction therapy followed by three courses of high-dose cytarabine consolidation. Only 3 months later, the patient relapsed with granulocytic sarcomas (GSs) in her rhinopharynx, external acoustic meatus, and bone marrow. She received focal radiation for the GSs and successfully underwent reinduction chemotherapy. Subsequently, she received a matched related donor peripheral blood stem cell transplantation followed by high-dose chemotherapy and is now in a second remission. We summarized 79 reported cases of t(8;21) AML with GS and reviewed the literature to identify differences in the characteristics of t(8;21) AML with GS between adults and children. To our knowledge, this is the first report of pharyngeal GS in t(8;21) AML, and focal irradiation plus more intensive postinduction therapy during first remission, such as allogeneic-SCT, may be effective in adult t(8;21) AML patients with GS.     

Allograft liver failure awaiting liver transplantation in Japan

Journal of Gastroenterology - Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the...     

Evaluation of Ethanol on Gastric Epithelial Restoration in Vitro

Ethanol exerts damaging effects on gastric mucosa and delays ulcer healing. To investigate the effect of ethanol on the wound repairing process, we used a wound repair model using primary cultured gastric mucosal cells. A confluent monolayer gastric mucosal cell sheet consisting mainly of mucous cells was wounded to make a cell-free area of constant size. Cell-free area was restored with time after wounding and monitored every 12 hr using a computer image analyzer to observe epithelial cell restoration quantitatively in the presence and absence of ethanol (2.0%). It was found that, although the control wound was completely repaired in 36 to 48 hr, the group treated with 2.0% ethanol showed a significant delay of repair. In the control, 5-bromodeoxyuridine-positive cells appeared around the wound in 24 to 36 hr. In contrast, the group treated with 2.0% ethanol showed no 5-bromodeoxyuridine-positive cells during the experiment. In conclusion, 2.0% ethanol retarded the repair of gastric mucosal restoration by inhibiting the initial gastric cell migration, followed by inhibition of proliferation of cells.     

Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

OBJECTIVES: We examined the effects of early treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on the progression of glucose intolerance and cardiovascular remodeling in a model of spontaneously developing type II diabetes mellitus (DM), the Otsuka Long-Evans Tokushima Fatty (OLETF) rats. BACKGROUND: Clinical trials showed that pravastatin prevented new-onset DM in hypercholesterolemic patients, and that it was effective in prevention of cardiovascular events in diabetics. METHODS: The OLETF rats were treated with pravastatin (100 mg/kg/day) from 5 weeks of age and compared with age-matched untreated OLETF rats and normal Long-Evans Tokushima Otsuka (LETO) rats on serial oral glucose tolerance tests (OGTT) and Doppler echocardiography and on histopathological/biochemical analyses of the heart at 30 weeks. RESULTS: The OGTT revealed that 40% and 89% of untreated OLETF rats were diabetic at 20 and 30 weeks, respectively, but 0% and only 30%, respectively, were diabetic in the treated OLETF. Left ventricular diastolic function was found impaired from 20 weeks in untreated OLETF but remained normal in the treated-OLETF. The wall-to-lumen ratio and perivascular fibrosis of coronary arteries were increased in untreated-OLETF but were limited in the treated-OLETF at 30 weeks. Moreover, cardiac expressions of a fibrogenic growth factor, transforming growth factor-beta1 (TGF-beta1), and a proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), were increased in untreated-OLETF. However, in the treated-OLETF, overexpressions of TGF-beta1 and MCP-1 were attenuated, which was associated with overexpression of endothelial nitric oxide synthase (eNOS) (2.5-fold of control LETO). CONCLUSIONS: Early pravastatin treatment prevented cardiovascular remodeling in the spontaneous DM model by retarding the progression of glucose intolerance, overexpressing cardiac eNOS, and inhibiting overexpressions of fibrogenic/proinflammatory cytokines.     

Helicobacter pylori is a fragile bacteria when stored at low and ultra-low temperatures

BACKGROUND AND AIM: Usually, bacteria are cryopreserved for short-term storage at low and ultra-low temperatures. There are no reports as to whether Helicobacter pylori is a fragile bacteria when stored at low and ultra-low temperatures as compared with other intestinal bacteria. A study was done on seven H. pylori strains and other intestinal bacteria to compare different temperatures for storage of organisms in saline solution. METHODS: Seven H. pylori strains, specifically American Type Culture Collection (ATCC) strains 43504 and TN2GF4, and five strains isolated from the present patients were grown on a modified Skirrow's agar for H. pylori. Escherichia coli and Bacteroides distasonis, both representing isolates from the present patients, were grown on trypticase soy blood agar for E. coli, and EG agar for B. distasonis. Culture was for 4-5 days under microaerobic, aerobic and anaerobic conditions at 37 degrees C. Cells were harvested by scraping growth from the solid medium and into sterile saline. The cells were adjusted to concentrations of 109 viable cells/mL in saline and preserved at 4 degrees C, -20 degrees C, or -80 degrees C for 3 weeks before reculture under microaerobic, aerobic and anaerobic conditions at 37 degrees C for 7 days. After incubation, morphologically distinct colonies were counted, isolated, and identified by standard bacteriologic techniques. The H. pylori were morphologically analyzed by electronic microscopy before and after preservation. Mongolian gerbils were inoculated with the cryopreserved H. pylori to evaluate the bacterial infectivity. RESULTS: Six of the seven H. pylori strains failed to culture after being preserved at 4 degrees C, -20 degrees C, or -80 degrees C. Only ATCC 43504 could be cultured after freezing at -80 degrees C. The number of H. pylori ATCC 43504 before preservation was 9.0 +/- 0.5 (log10 no. organisms/mL) and decreased to 5.7 +/- 0.6 after preservation. Morphologically, all H. pylori except ATCC 43504 strains transformed from a bacillary to a coccoid form after preservation. In addition, none of the H. pylori strains could infect Mongolian gerbils after preservation. Escherichia coli and B. distasonis were recovered. Titers before and after 4 degrees C, -20 degrees C, and -80 degrees C, respectively, were 9.1 +/- 0.2, 8.9 +/- 0.5, 8.6 +/- 0.3, and 8.7 +/- 0.3 for E. coli and 9.1 +/- 0.4, 8.7 +/- 0.6, 8.6 +/- 0.5, and 8.8 +/- 0.3 for B. distasonis. CONCLUSIONS: Helicobacter pylori is a fragile bacteria for storage at low and ultra-low temperatures in comparison with other intestinal bacteria.     

Exercise after heparin administration: new therapeutic program for patients with-option arteriosclerosis oblitrans.

BACKGROUND: A prospective study examined whether a combination of an exercise program and heparin administration improves the clinical symptoms of patients with arteriosclerosis obliterans (ASO) without an indication for surgical revascularization because of the lack of distal target vessels or other reasons such as high surgical risk or lack of a vein conduit from previous coronary artery bypass surgery. METHODS AND RESULTS: A total of 19 consecutive patients with symptomatic non-option ASO diagnosed by angiography were randomly assigned to 3 groups: heparin + exercise (walking for 60 min after heparin injection [3,000 units/day IV for 14 days], n = 6), heparin administration only (n = 6), and exercise only (n = 7). Plasma levels of hepatocyte growth factor (HGF) were serially measured before and after intravenous administration of heparin. Ankle brachial pressure index was measured and treadmill exercise test (2.5 km/h, 12% slope) was performed before the 2-week treatment, just after finishing treatment, and 12 weeks after beginning the treatment. Ophthalmic examinations, including visual acuity test, ocular fundoscopy and fluorescein angiographic fundus photography, were performed before and 12 weeks after the treatment program. In all patients, HGF levels increased more than 4-fold of the basal level at 30 min after heparin injection. Maximum walking time was significantly higher in the heparin + exercise group than in the other 2 groups (p < 0.05). There were no patients who showed pathological retinal angiogenesis. CONCLUSION: The combination of an exercise program and heparin administration improves the clinical symptoms of patients with non-option ASO.