Glycogen synthase kinase-3beta is involved in the process of myocardial hypertrophy stimulated by insulin-like growth factor-1.

BACKGROUND: Glycogen synthase kinase-3 beta (GSK-3beta) is involved in many cellular processes, such as metabolism, apoptosis, differentiation and proliferation. Insulin-like growth factor-1 (IGF-1), which is well known to have a hypertrophic effect on cardiomyocytes, inactivates (phosphorylates) GSK-3beta in some cell types. The role of GSK-3beta in cardiomyocytes as a negative regulator of cardiac hypertrophy has been recently reported and the present study investigated the role of GSK-3beta in the cardiac hypertrophy of cultivated neonatal rat cardiomyocytes induced by IGF-1. METHODS AND RESULTS: First, the IGF-1 induced signal transduction leading to GSK-3beta in neonatal rat cardiomyocytes was examined. The phosphatidylinositol (PI) 3-kinase/Akt/GSK-3 beta signaling induced by IGF-1 was investigated using inhibitors of PI 3-kinase and Ad AktAA, a dominant negative form of Akt. Furthermore, using Ad MEK DN, a dominant negative form of MEK, it was found that MEK negatively regulates Akt phosphorylation upon IGF-1 stimulation. Next, it was examined whether GSK-3beta acts as a negative regulator in the cardiac hypertrophy induced by IGF-1. Sustained stimulation by IGF-1 caused cardiac hypertrophy in protein synthesis and cellular morphology, and overexpression of unphosphorylatable GSK-3beta (Ad GSK-3beta S9A) repressed these hypertrophic effects of IGF-1. CONCLUSIONS: GSK-3beta may play an important role as a negative regulator of cardiac hypertrophy induced by IGF-1.     

Effect of 24-hour ureteral obstruction on subsequent ischemic damage in rat kidney

The effects of prior 24-hour ureteral obstruction on ischemic renal damage were studied in rats. Rats were divided into 6 groups with different times of ischemia (0, 60 and 90 min) and with or without 24-hour ureteral obstruction. Following a 4-week recovery period, contralateral nephrectomy was performed and the rat was sacrificed 24 h later for the determination of serum creatinine and for histologic examination of the affected kidney. A preceding ureteral obstruction for 24 h made no difference to the renal damage with 60 min of ischemia or without ischemia. However, kidneys with 90 min of ischemia and 24 h of ureteral obstruction were more damaged than those with 90 min of ischemia only. These results suggested that the hydronephrotic kidney was more susceptible to long periods of ischemia than the normal kidney.     

Detection of Platelet Antibody Using Rosette Technique with Anti-IgG Antibody-Coated Polyacrylamide Gel

Abstract. Paraformaldehyde-fixed platelets from normal donors were used for detection of antibody to platelet by in vitro sensitization (indirect method) utilizing rabbit anti-human IgG heavy chain specific antibody-coated polyacrylamide gels (Immunobeads). The sensitized platelets formed rosettes with Immunobeads and the positive rosette count was over 30%, while control showed less than 8% when normal sera were used. This method was also applicable for detecting antibody-sensitized platelets in vivo (direct method) in patients with autoimmune thrombocytopenia. This method is simple, rapid and reproducible for clinical use. Direct and indirect immunofluorescent antibody tests and a blocking test with anti-human serum also supported the results of Immunobead rosetting technique.     

Implications of Popliteal Lymph Node Detected by Sentinel Lymph Node Biopsy

BACKGROUND: Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy. METHODS: Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy. RESULTS: In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node. CONCLUSION: This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.     

Bezafibrate improves hypertension and insulin sensitivity in humans.

We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140 +/- 2.6 to 131.8 +/- 2.6 mmHg, mean +/- SEM), diastolic blood pressure (DBP) (87.8 +/- 2.0 to 82.8 +/- 2.6 mmHg), fasting plasma triglyceride concentration (225.5 +/- 23.5 to 102.9 +/- 10.9 mg/dl), fasting plasma insulin concentration (9.6 +/- 0.8 to 7.1 +/- 0.8 microU/ml), and homeostasis model assessment scores (HOMA-R, 2.4 +/- 0.2 to 1.7 +/- 0.2), and significantly improved the insulin sensitivity index (56.0 +/- 3.0 to 70.7 +/- 4.8 mg x l2/mmol x mU x min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r = 0.50, p < 0.01) and SFA (r = 0.39, p < 0.05), and negatively correlated with PUFA (r = -0.45, p < 0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders.     

Thallium-201 SPECT depicts radiologically occult lung cancer.

A case of radiologically occult lung cancer is presented in which 201TI SPECT of the chest clearly delineated the involved area. A 66-yr-old man underwent chest screening examinations for asymptomatic smokers and presented a positive sputum cytology for lung cancer. Conventional chest x-ray, tomography of computed radiography, and a CT scan failed to locate the lesion in the lung. Thallium-201 SPECT, however, was successful in depicting the area of the involvement.     

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.