Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

A Case of Herpes Zoster Associated with Colitis

A 58-year-old Japanese woman who had herpes zoster in association with colitis was successfully treated with intravenously administrated acyclovir. Vesicular lesions with red haloes ranged from the left side of her buttock to the left extremity, corresponding to the L4 to S2 dermatomes. Her colitis was considered to have been induced by varicella-zoster virus, based on the facts that the clinical courses were correlated and that the innervation of the affected site of the colon corresponded to an infected dermatome (S2).     

An Autopsy Case of Dermatomyositis with Rapidly Progressive Diffuse Alveolar Damage

A 47-year-old woman visited a clinic with dyspnea which had continued for two months and was followed by general fatigue and fever. Antibiotics were not effective. Edematous erythema occurred on her face, elbows, knees and feet, and she entered our hospital. A skin biopsy revealed interface dermatitis with severe edema and mucinosis in dermis. Diffuse bilateral infiltration was observed in the chest X-ray, and laboratory findings showed increased LDH, GPT, GOT and CPK. No antinuclear factor was detected. Her respiratory condition rapidly worsened, and she died eight days after hospitalization in spite of corticosteroid pulse therapy. The autopsy revealed that the main cause of death was diffuse alveolar damage (DAD). Interstitial pneumonia related to dermatomyositis is not histologically uniform; the response to the therapy depends on its histological type. The patients with dermatomyositis who have poor prognosis are clinically characterized by acute onset with general symptoms and less pronounced muscle weakness; they generally show DAD in their lungs. We need to establish a simple method for distinguishing histological types of interstitial pneumonia and adequate therapy for each one.     

Effects of Intestinal and Hepatic Metabolism on the Bioavailability of Tacrolimus in Rats

Purpose. Tacrolimus, an immunosuppressive agent, has poor and variable bioavailability following oral administration in clinical use. We investigated the contribution of intestinal metabolism to the first pass effect of tacrolimus in rats. Methods. Tacrolimus was administered intravenously, intraportally or intraintestinally to rats. Blood samples were collected over a 240-min period, and blood tacrolimus concentrations were measured. The extraction ratios of tacrolimus in the intestine and liver were investigated. In addition, the metabolism of tacrolimus in the everted sacs of the small intestine was examined. Results. The rate of absorption of tacrolimus in the intestine was rapid, and tacrolimus was almost completely absorbed after intestinal administration. The bioavailability of tacrolimus was about 40% and 25% after intraportal and intraintestinal administration, respectively, indicating that tacrolimus is metabolized in both the intestine and the liver. In addition, tacrolimus was significantly metabolized in the everted sacs of the rat intestine. Conclusions. The present study suggested that the metabolism of tacrolimus in the intestine contributes to its extensive and variable first pass metabolism following the oral administration.     

Involvement of MMP-7 in invasion of pancreatic cancer cells through activation of the EGFR mediated MEK-ERK signal transduction pathway

AIMS: To clarify the involvement of matrix metalloproteinase-7 (MMP-7) in cell dissociation and the subsequent invasion of pancreatic cancer cells.METHODS: Western blotting, in vitro invasion assay, immunocytochemistry, and immunohistochemistry were performed in pancreatic cancer cell lines or pancreatic cancer tissue.RESULTS: The active form of the MMP-7 protein was expressed exclusively in the conditioned medium of dissociated (PC-1.0 and AsPC-1) pancreatic cancer cells, whereas proMMP-7 protein was only detected in the conditioned medium of non-dissociated (PC-1 and Capan-2) cells. Both intracellular and conditioned medium localised MMP-7 was greatly reduced by treatment with the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the mitogen activated protein kinase kinase (MEK) inhibitor U0126 in pancreatic cancer cells. MMP-7 treatment significantly induced the disruption of tight junction (TJ) structures and subsequent cell dissociation, and activation of the EGFR mediated MEK- ERK (extracellular signal regulated protein kinase) signalling pathway in the non-dissociated pancreatic cancer cells. Moreover, the strong in vitro invasiveness of dissociated cells was inhibited by AG1478 and U0126 treatment, whereas the weak invasiveness of non-dissociated cells was apparently induced by MMP-7 treatment. In addition, MMP-7 expression was stronger at the invasive front than at the centre of human pancreatic tumours.CONCLUSION: MMP-7 is involved in cell dissociation and the subsequent invasion of pancreatic cancer cells. It induces the disruption of TJ structures and forms a positive feedback loop with activation of the EGFR mediated MEK-ERK signalling pathway.     

Mechanical power during maximal treadmill walking and running in young and elderly men

This study determined mechanical power during movements specific to maximal walking and running using a non-motorized treadmill in 38 elderly [69.4 (5.0) years] and 50 young [24.3 (3.4) years] men. The mean mechanical power over a period of time covering six steps, during which the belt velocity peaked and then kept almost plateau, was determined as a performance score in each of maximal walking (WP) and running (RP). In terms of the value relative to body mass, the relative difference between the two age groups was greater for RP (61.7%) than for WP (21.4%) or isometric knee extension (34.1%) and flexion torque (43.8%). In the two groups, WP was significantly (P<0.05) correlated to knee extension (r=0.582 for the elderly and r=0.392 for the young) and flexion torque (r=0.524 for the elderly and r=0.574 for the young). Similarly, RP was also significantly (P<0.05) correlated to knee extension (r=0.627 for the elderly and r=0.478 for the young) and flexion torque (r=0.500 for the elderly and r=0.281 for the young). In these relationships, the WP adjusted statistically by thigh muscle torque was similar in the two age groups. However, the corresponding value for RP was significantly higher in the young than in the elderly. The findings here indicate that: (1) the difference between the young and elderly men in mechanical power is greater during maximal running than maximal walking, and (2) although the thigh muscle torque contributes to the power production during the two maximal exercise modes in the two age groups, the RP is greater in the young than in the elderly regardless of the difference in the thigh muscle torque.     

Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review

Stenosis at the graft–vein junction caused by intimal hyperplasia (IH) is the major cause of failure of vascular access grafts used for hemodialysis. There is a strong relationship between hemodynamic factors and formation of IH. The hemodynamic pattern and the location of IH are different in arterial bypass grafts (ABGs) compared with arteriovenous grafts (AVGs). In an ABG, end-to-side anastomosis of the expanded polytetrafluoroethylene graft and artery produces hemodynamic changes around the junction. IH develops at the arterial floor and the toe and heel of the distal anastomosis. Low shear stress and oscillating shear forces at the arterial floor and the heel plus a high wall sheer stress (WSS) gradient at the toe probably promote IH development. Compliance mismatch between the graft and artery causes turbulence that may contribute to IH formation. The blood flow rate in AVGs is 5–10 times greater than that in ABGs. High flow causes turbulence that injures endothelial cells and eventually results in IH. The peak WSS in AVGs is about 6N/m², much higher than that in ABGs. Excessively high WSS may effect IH formation in AVGs. Several venous cuff or patch anastomotic designs have been used in attempts to regulate hemodynamic factors in grafts. In ABGs, these designs appear to help decrease IH formation. In AVGs, however, they generally have not improved patency rates. In a high-flow system such as an AVG, more drastic changes in anastomotic design may be required.     

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(–273)C (P=0.0074), C(–297)T (P=0.0195), and IMS-JST071749 (P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(–273)C genotype was influential in another set of subjects (P=0.0310, n=743). However, the distribution of the ABCA1 G(–273)C genotype in subjects with MI (n=598) was not different from that in the control population (n=801). These results indicate that ABCA1 G(–273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.     

GIANT CELL CARCINOMA OF THE PANCREAS

A case of giant cell carcinom of the pancreas is reported herein. The patient is a 67-year-old Japanese woman complaining of ascites, general fatigue, loss of weight, abdominal distention, nausea, and vomiting. Cytological diagnosis of ascites revealed adenocarcinoma. At autopsy, a whitish tumor measuring around 5 cm in diameter was found at the head of the pancreas. Metastasis was seen only in the liver. Histological examination displayed bizarre multinucleated giant cells occasionally phagocytosing the tumor cells and neutrophils.