Immunohistochemical study of the kidneys after severe muscular injury

Severe muscular injury sometimes causes renal failure, and myoglobin in skeletal muscle is known to induce toxic free oxygen radicals in the kidneys. The relationship between the immunohistochemical expression of myoglobin and the scavenger copper/zinc superoxide dismutase (Cu/Zn-SOD) was investigated in kidneys taken from two autopsy groups, a group with tourniquet shock (n = 4), and a group with severely injured skeletal muscle (n = 18). Paraffin-embedded kidney sections were used for immunohistochemical staining by the avidin-biotin-complex (ABC) method using antibodies against myoglobin and Cu/Zn-SOD. Detection of the two antigens was analyzed qualitatively. In most cases of tourniquet shock in which the survival time was considered to be relatively long, myoglobin staining was positive and Cu/Zn-SOD was negative. Among the seven cases of severely injured skeletal muscle in which the survival period was considered to be relatively short, positive staining was detected immunohistochemically for both myoglobin and Cu/Zn-SOD. Moreover, in most of the cases in this group that showed acute tubular necrosis, immunohistochemical staining was negative for both markers, whereas positive staining was found for most of the cases in which the kidneys were revealed to be normal by HE staining. These findings suggest that when myoglobin enters the kidneys via the circulation, Cu/Zn-SOD reacts to eliminate free radicals, but is depleted by consumption in the long run, and that there might be a relationship between these histological findings and immunohistochemical expression. Received: 2 December 1999 / Accepted: 22 May 2000     

Prostatic carcinoma presenting as neck lymph node metastases: report of two cases]

We report two cases of prostatic carcinoma presenting as neck lymph node metastases. Case 1: A 56-year-old man was admitted to our hospital with the chief complaint of left lower abdominal pain. A lymph node was palpable on the left side of the neck swollen. Rectal examinations revealed prostatic stony-hard mass. Computed tomography showed a swollen neck and paraaortic lymph nodes on the left side. PSA level was 380 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma, and neck lymph node biopsy also revealed metastatic adenocarcinoma. We diagnosed him with prostatic carcinoma stage D2 (LYM). He underwent hormonal therapy (TAB) but died 13 months later. Case 2: A 66-year-old man was admitted to our hospital with the chief complaint of a large palpable mass on the left side of the neck. Resection of this mass revealed metastatic adenocarcinoma. Rectal examination revealed no malignant lesions, but the PSA level was high, 1,700 ng/ml. Transperineal prostatic biopsy revealed moderately differentiated adenocarcinoma. Computed tomography revealed paraaortic and pelvic lymph node metastases and bone scintigram revealed abnormal uptake, bone metastases. We diagnosed him with prostatic carcinoma stage D2 (LYM OSS). We performed bilateral testectomy followed by hormonal therapy (TAB). The lymph node metastases disappeared after 4 months of therapy.     

Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet�CInduced Obesity: Importance of Hepatic Lipogenesis

OBJECTIVE

Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.

RESEARCH DESIGN AND METHODS

Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4–20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.

RESULTS

Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.

CONCLUSIONS

This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.The metabolic syndrome has been defined as a cluster of visceral fat obesity, impaired glucose metabolism, atherogenic dyslipidemia (high plasma triglyceride and low HDL cholesterol), and hypertension (1). There is considerable evidence that visceral fat obesity is a key etiological factor in the metabolic syndrome (2). Enhanced hepatic lipogenesis and hepatic steatosis also appear to play an important role in the pathogenesis of the metabolic syndrome (3). Indeed, nonalcoholic fatty liver disease may constitute the common features of the metabolic syndrome.Numerous epidemiological studies and clinical trials have revealed that fish oil and n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of coronary heart disease (4). Eicosapentaenoic acid (EPA), one of the major n-3 PUFAs contained in fish oil, has a variety of pharmacological effects such as lipid-lowering (5), anti-platelet (6), anti-inflammatory (7), and anti-atherogenic effects (8,9). Recently, the Japan EPA Lipid Intervention Study (JELIS), a large-scale prospective randomized clinical trial, demonstrated that EPA delays the onset of cardiovascular events via cholesterol-independent mechanisms (10,11), but the molecular mechanisms remain to be elucidated. In a recent sub-analysis of the JELIS, EPA had a great risk reduction of coronary artery events of 53% in patients with high triglycerides and low HDL cholesterol (11), suggesting that EPA may be effective to reduce the incidence of atherosclerosis in the metabolic syndrome. These findings are supported by our recent observations that EPA administration results in decreases in remnant-like particle-triglyceride, small dense LDL, and C-reactive protein and an increase in adiponectin in patients with the metabolic syndrome (12,13).Given the pleiotropic effect of EPA, it is interesting to know whether highly purified EPA is capable of improving obesity. There is currently a controversy as to the anti-obesity effect of EPA; it has been effective (13,14), has been ineffective (15), or has even increased visceral fat accumulation (16). On the other hand, it is noteworthy that EPA suppresses hepatic lipogenesis and steatosis by reducing mRNA and active protein of sterol regulatory element binding protein-1c (SREBP-1c) (17–19). We, therefore, examined the impact of hepatic lipogenesis on the anti-obesity effect of highly purified EPA.Here, we demonstrate that EPA strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in high-fat (HF)/high-sucrose (HS)-induced obese mice with enhanced hepatic lipogenesis but not in HF-induced obese mice without enhanced hepatic lipogenesis. This study is the first demonstration that the anti-obesity effect of EPA is related to the suppression of hepatic lipogenesis. Given that the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data of this study suggest that EPA is suited for the treatment of the metabolic syndrome.     

Impact of Pump Replacement on Outcome in Advanced Heart Failure Patients With Left Ventricular Assist System

Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system (LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m² was a significant predictor of pump replacement (hazard ratio [HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke (P < 0.05) as well as a significantly greater decrease in body weight (F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2‐year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality (HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS.     

Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.     

The beneficial effect of superoxide dismutase on the rat liver graft

We performed orthotopic liver transplantation in male Wistar rats and investigated the effect of superoxide dismutase (SOD) on the liver graft. Animals were divided into the four following experimental groups. Group I was an untreated control group, group II received oxygen, group III received SOD and group IV received both oxygen and SOD. The dose of SOD was 3 mg/kg which was injected intravenously into both donors and recipients during the operation. Oxygen was given through an oxygen inhaler to both donors and recipients during the operation. The preservation time of the liver graft ranged from 4 hours and 41 minutes to 5 hours and 40 minutes. The survival after liver transplantation was compared among groups I, II, III and IV. Group IV showed a significantly higher survival rate than groups I and II by two weeks after liver grafting, but there was no statistical difference in the survival rates between groups III and IV. These results indicate the beneficial effect of SOD on the rat liver graft and may implicate oxygen free radicals in the pathogenesis of ischemia/reperfusion injury in liver grafts.     

Prevalence and time of appearance of Brugada electrocardiographic pattern in young male adolescents from a three-year follow-up study

The prevalence of Brugada's electrocardiographic (ECG) pattern in 7,022 male adolescents in the seventh grade was determined, and the same subjects were reexamined 3 years later, while in tenth grade. Two subjects (0.03%) and 7 subjects (0.10%) showed Brugada's ECG pattern by the conventional criterion (J point or ST-segment >/=0.1 mV in leads V(1) to V(3)), and no subjects (0%) and 2 subjects (0.03%) fulfilled the recent criterion (J point or ST-segment >/=0.2 mV) in the seventh and tenth grades, respectively, indicating that Brugada's ECG pattern begins to appear during junior high school and increases until late adulthood.     

A case of postpartum fever caused by Mycoplasma hominis infection

A 26-year-old housewife was admitted to our hospital with a history of high fever after previous cesarean delivery. She had premature rupture of the membrane on the 41st week of pregnancy and the amniotic fluid was found to be cloudy on the fourth day after rupture. Therefore, cesarean delivery was performed. On the first day of operation, her body temperature increased up to 38 degrees C in spite of the treatment with Latamoxef (LMOX), 3 g/day. A sample of intrauterine material yielded M. hominis in pure culture. After administration of Minocycline (MINO) with antimycoplasmal activity, the clinical symptoms improved by the 11th day of operation. Sera obtained after the infection showed antibodies to M. hominis in ELISA study. These results suggested that the cause of this postpartum fever was M. hominis infection.