Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.     

Effects of home-based combined resistance training and walking on metabolic profiles in elderly Japanese

Background: To evaluate the effects of home‐based combined resistance training and walking on metabolic profiles in elderly Japanese subjects. Methods: Two hundred and forty‐four elderly Japanese participants were divided into two groups (184 training group and 60 controls). Each exercise training session consisted of one set of 10 repetitions of 11 different resistance exercises, and the training lasted 12 weeks. Fasting blood samples were obtained for measurements of serum levels of total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, hemoglobin A_1c, insulin and plasma glucose, before and after the training period. We estimated insulin resistance using the homeostasis model assessment. Five subjects further underwent a two‐step hyperinsulinemic‐euglycemic clamp to evaluate insulin action directly before and after the training. Results: Training resulted in a significant increase in HDL‐C (60 ± 1–62 ± 1 mg/dL, mean ± SE, P < 0.01) and a significant decrease in triglycerides (115 ± 5–106 ± 4 mg/dL, P < 0.05), while no significant changes were observed for total cholesterol, plasma glucose, insulin, homeostasis model assessment or hemoglobin A_1c. Glucose infusion rates during the hyperinsulinemic‐euglycemic clamp increased by 30% (P < 0.05) at the 40 mU/m² per min infusion rate, from 5.4 ± 0.9 to 7.0 ± 1.1 mg/kg per min and by 15% (P < 0.01) at the 400 mU/m² per min infusion rate, from 9.4 ± 1.0 to 10.8 ± 1.2 mg/kg per min. In the control group, no significant changes were noted except for a significant decrease in HDL‐C. Conclusions: Our home‐based exercise program for elderly is safe and effective for improving metabolic profiles.     

Influence of contrast ultrasonography with perflutren lipid microspheres on microvessel injury.

Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0 ml/kg) or Levovist (300 mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0 ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting.     

Surgical management for the prevention of pancreatic fistula following distal pancreatectomy

Although the mortality rate related to pancreatic surgery has been reduced recently, the postoperative morbidity is still high, because of various complications. Pancreatic fistula is one of the most common complications following distal pancreatectomy, and is generally hard to cure. Several surgical techniques and devices, such as the use of fibrin-glue sealing, stapler closure, an ultrasonic dissector, or an ultrasonically activated scalpel have been advocated to prevent pancreatic fistula. In the present review we provide an overview of several devices used for the prevention of pancreatic fistula following distal pancreatectomy.     

Optimal relaxation parameters of dynamic row-action maximum likelihood algorithm and post-smoothing filter for image reconstruction of dedicated breast PET

Annals of Nuclear Medicine - This study aimed to determine the optimal β value of the relaxation control parameter and the post-smoothing filter in the list-mode dynamic row-action maximum...     

Design and creation of a Ca2+ binding site in human lysozyme to enhance structural stability.

A Ca2+ binding site like an EF-hand motif was designed and created in human lysozyme by replacing both Gln-86 and Ala-92 with aspartic acids by site-directed mutagenesis. The mutant human lysozyme (D86/92-lysozyme) was expressed and secreted by yeast. One Ca2+ was found to bind one molecule of the purified protein with the binding constant 5.0 x 10(6) M-1. The enzymatic activity of holo-D86/92-lysozyme against glycol chitin at 40 degrees C was 2-fold higher than that of the native lysozyme. Maximal activity of the holo-D86/92-lysozyme was observed at 80 degrees C, where its relative activity normalized to the value at 40 degrees C was 6-fold and 17-fold higher than those of the native and apoenzymes, respectively. The activities of the native lysozyme and apo-D86/92-lysozyme were maximum at 65 degrees C-70 degrees C. Moreover, D86/92-lysozyme was more stable against protease digestion than the native lysozyme. These results indicate that the creation of the calcium binding site like an EF-hand motif in the human lysozyme enhances its structural stability.     

Effects of aerobic and resistance exercise training on insulin action in the elderly

Background:   Aging is associated with a declining glucose tolerance, which is primarily caused by peripheral insulin resistance, and with a decline in physical activity. The aim of this study was to assess the effect of aerobic and resistance exercise training on insulin action in the elderly.
Methods:   Fourteen healthy male subjects (age: 65–73 years) were enrolled and divided into two exercise groups: resistance training (RT) or a combined aerobic and resistance training (CT). Subjects participated in each training program three times a week for 12 weeks. Before and after the training program, insulin action was determined using the euglycemic clamp technique at insulin infusion rates of 40 (low) or 400 (high) mU/m² per min. Body composition was measured by dual-energy X-ray absorptiometry (DXA).
Results:   Percent fat decreased significantly in both groups. Fat-free mass (FFM) tended to increase in the RT group ( P  = 0.054), but not in the CT group. In the CT group, the glucose infusion rate (GIR) increased 16.6% ( P  < 0.05) at the low insulin infusion rate and 21.7% ( P  < 0.01) at the high rate. In the RT group, GIR tended to increase at the low insulin infusion rate, but was not statistically significant ( P  = 0.052) and increased 9.9% ( P  < 0.05) at the high rate. When calculated per FFM, the increased insulin action persisted in the CT group ( P  < 0.01), but not in the RT group.
Conclusion:   The combination of aerobic and resistance training is more effective for improving the decreased insulin action in the elderly than resistance training alone.     

Src family kinases and nitric oxide production are required for hepatocyte growth factor-stimulated endothelial cell growth

Hepatocyte growth factor (HGF) is a potent mitogen for vascular endothelial cells (EC); however, signal transduction pathways for HGF-stimulated EC growth remain unclear. In the present study we investigated the role of Src family kinases and nitric oxide (NO) in HGF-stimulated EC growth. Human umbilical vein endothelial cells (HUVEC) were stimulated with HGF and NO was measured by an NOx analyzing HPLC system. Activation of ERK1/2 and p38 MAPK was assessed by Western blot. NO production in HUVEC increased 1.8-fold by HGF. A Src family kinases inhibitor PP1 inhibited HGF-stimulated NO production by 71%. HUVEC growth increased 1.9-fold in cell number by HGF. PP1 and Nitro-L-arginine methylester (L-NAME) inhibited HGF-stimulated HUVEC growth by 51 and by 71%. ERK1/2 and p38 MAPK were phosphorylated by HGF and a MEK inhibitor PD98059 and a p38 MAPK inhibitor SB203580 inhibited HGF-stimulated HUVEC growth by 66% and by 58%; however, HGF-induced phosphorylation of ERK1/2 and p38 MAPK was not inhibited by L-NAME, indicating that NO is not an upstream activator of ERK1/2 and p38 MAPK. These findings demonstrated that Src family kinases regulate HGF-stimulated NO production in HUVEC and that HGF stimulates HUVEC growth through NO-dependent and NO-independent pathways.     

Relationship between the weight-bearing ratio on the affected lower extremity and gait ability using a portable electronic foot sensor shoe (Step Aid?) in hemiplegic stroke patients

[Purpose] This study investigated the association between the weight-bearing ratio (WBR) and gait ability of a paretic lower limb while walking using a shoe-type load-measuring apparatus. [Subjects] The Subjects comprised 17 stroke patients who were classified into the following two groups: the independent walking group, and the non-independent walking group. [Methods] The 10-m walking time (inside and outside parallel bars) and the Berg Balance Scale (BBS) were measured. The WBR of the paretic lower limb was measured during static standing and while walking inside and outside parallel bars, and the coefficient of variation (CV) was calculated. WBR was evaluated using the Step Aid. [Results] The BBS and WBR were significantly decreased in the non-independent walking group, while the 10-m walking time and the CV were significantly increased in the non-independent walking group. [Conclusion] The CV and WBR of a paretic lower limb while walking appear to be important indices of achievement of independent gait in hemiplegic stroke patients, and they may be used in gait rehabilitation for diseases requiring weight-bearing training to follow the course of training using a shoe-type load-measuring apparatus.Key words: Stroke, Weight-bearing ratio, Shoe-type load-measuring apparatus