A device for adsorbing unbound, unconjugated bilirubin and its effects in vitro and in a hyperbilirubinemic newborn piglet

AIMS: A novel blood purification material that we previously reported as a superantigen- and cytokine-adsorbing device (SCAD) was evaluated for its ability to adsorb unbound, unconjugated bilirubin (UUBil) in vitro and in vivo. METHODS: In albumin-containing buffer, UUBil was dissolved and circulated through the SCAD column. Also, bilirubin was infused into low-body weight newborn piglets and hemoperfused for 3 h over SCAD columns. RESULTS: In albumin-containing buffer, concentration of bilirubin decreased from 34 to 0.6 mg/dL within 5 h and the SCAD fiber turned brown, indicating that bilirubin was adsorbed onto the surface of the adsorbent and was not degraded during the circulation. Using the hyperbilirubinemia swine, clearances of total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IdBil) were significantly higher (P<0.01) in the SCAD group compared with the control group. The clearances of TBil, DBil, and IdBil at 3 h after the initiation of the bilirubin infusion were 0.47, 0.53, and 0.45 mL/min, respectively, at a blood flow rate of 2.5 mL/min, and this result indicates that almost 20% of bilirubins were adsorbed to the SCAD column in a single passage. CONCLUSION: These results provide initial evidence that SCAD treatment is effective in the removal of UUBil and can be performed safely in newborn animals.     

Gene Expression Profile Provides Novel Insights of Fasting-Refeeding Response in Zebrafish Skeletal Muscle

Recently, fasting has been spotlighted from a healthcare perspective. However, the de-tailed biological mechanisms and significance by which the effects of fasting confer health benefits are not yet clear. Due to certain advantages of the zebrafish as a vertebrate model, it is widely utilized in biological studies. However, the biological responses to nutrient metabolism within zebrafish skeletal muscles have not yet been amply reported. Therefore, we aimed to reveal a gene expression profile in zebrafish skeletal muscles in response to fasting-refeeding. Accordingly, mRNA-sequencing and bioinformatics analysis were performed to examine comprehensive gene expression changes in skeletal muscle tissues during fasting-refeeding. Our results produced a novel set of nutrition-related genes under a fasting-refeeding protocol. Moreover, we found that five genes were dramatically upregulated in each fasting (for 24 h) and refeeding (after 3 h), exhibiting a rapid response to the provided conditional changes. The assessment of the gene length revealed that the gene set whose expression was elevated only after 3 h of refeeding had a shorter length, suggesting that nutrition-related gene function is associated with gene length. Taken together, our results from the bioinformatics analyses provide new insights into biological mechanisms induced by fasting-refeeding conditions within zebrafish skeletal muscle.     

Increased insulin sensitivity and hypoinsulinemia in APS knockout mice

A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS(-/-) mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS(-/-) mice was increased over that of APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.     

Vertebral derotation in adolescent idiopathic scoliosis causes hypokyphosis of the thoracic spine

The underlying purpose of this commentary and position paper is to achieve evidence-based recommendations on prevention of work-related musculoskeletal disorders (MSDs). Such prevention can take different forms (primary, secondary and tertiary), occur at different levels (i.e. in a clinical setting, at the workplace, at national level) and involve several types of activities. Members of the Scientific Committee (SC) on MSDs of the International Commission on Occupational Health (ICOH) and other interested scientists and members of the public recently discussed the scientific and clinical future of prevention of (work-related) MSDs during five round-table sessions at two ICOH conferences (in Cape Town, South Africa, in 2009, and in Angers, France, in 2010). Approximately 50 researchers participated in each of the sessions. More specifically, the sessions aimed to discuss new developments since 1996 in measures and classification systems used both in research and in practice, and agree on future needs in the field. The discussion focused on three questions: At what degree of severity does musculoskeletal ill health, and do health problems related to MSDs, in an individual worker or in a group of workers justify preventive action in occupational health? What reliable and valid instruments do we have in research to distinguish ??normal musculoskeletal symptoms?? from ??serious musculoskeletal symptoms?? in workers? What measures or classification system of musculoskeletal health will we need in the near future to address musculoskeletal health and related work ability? Four new, agreed-upon statements were extrapolated from the discussions: 1. Musculoskeletal discomfort that is at risk of worsening with work activities, and that affects work ability or quality of life, needs to be identified. 2. We need to know our options of actions before identifying workers at risk (providing evidence-based medicine and applying the principle of best practice). 3. Classification systems and measures must include aspects such as the severity, frequency, and intensity of pain, as well as measures of impairment of functioning, which can help in prevention, treatment and prognosis. 4. We need to be aware of economic and/or socio-cultural consequences of classification systems and measures.     

Correlation of unilateral thoracoscopic lung volume reduction with improvement in lung function and exercise performance in patients with severe pulmonary emphysema

1 ), forced vital capacity, static compliance, and maximal oxygen uptake. The functional residual capacity as measured by the gas dilution method (FRC_gas), was unchanged; however, it was found to be decreased significantly when measured by body plethysmograph (FRC_box). Positive correlations existed between the reduction in FRC_box and the increase in FEV₁ (r = 0.586, P = 0.0042) and maximal oxygen uptake (r = 0.550, P = 0.018). Pulmonary ventilation and exercise ability in patients with pulmonary emphysema were improved in a volume-dependent manner by thoracoscopic lung volume reduction. These findings indicate that patients with a preoperative trapped gas volume level exceeding 1 l would be ideal candidates for thoracoscopic lung volume reduction. (Received for publication on Mar. 4, 1998; accepted on Jan. 7, 1999)     

Skip mediastinal nodal metastases in non-small cell lung cancer

Objective: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases (‘skip-N2 metastases’) in non-small cell lung cancer (NSCLC). Methods: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. Results: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. Conclusions: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.     

Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney

Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones.     

Preoperative imaging of the lung sentinel lymphatic basin with computed tomographic lymphography: a preliminary study

BACKGROUND: Preoperative localization of the sentinel node basin would guide selective lymph node dissection. We tried to identify these nodal stations with indirect computed tomographic lymphography using a conventional extracellular contrast agent, iopamidol. METHODS: Eleven consecutive patients scheduled to undergo anatomic resection of suspected lung cancer, without lymphadenopathy, were given a peritumoral injection of undiluted iopamidol under computed tomography guidance, and lymphatic migration was assessed by multidetector-row helical computed tomography. RESULTS: There were no complications such as bleeding, pneumothorax, or allergic reactions. Enhanced nodes were detected in all but 1 patient who had diffuse lymph nodal calcification. Enhanced nodes were identified at 32 ipsilateral intrathoracic nodal stations (20 hilar stations and 12 mediastinal stations). The average length of the longer axis of the enhanced nodes was 4.8 mm (range, 3 to 8 mm), and the average attenuation of the enhanced nodes was 132 (range, 46 to 261) Hounsfield units. In 9 patients with confirmed lung cancer, enhanced nodes appeared at 26 nodal stations, and all apparent enhanced nodes were identified as actual lymph nodes at appropriate position during lymphadenectomy. None of the resected lymph nodes had metastatic involvement. CONCLUSIONS: Indirect computed tomographic lymphography with the peritumoral injection of iopamidol effectively depicts the drainage nodes unless they are diffusely calcified. Although further study is required, this method could guide selective lymph node dissection.