Increased urinary levels of pentosidine,pyrraline and acrolein adduct in type 2 diabetes

This study investigates whether urinary levels of pentosidine, pyrraline and acrolein adduct are increased in type 2 diabetes (DM), and whether these levels are correlated with glycemic control and clinical traits. Urinary levels of pentosidine, pyrraline and acrolein adduct in DM patients (n = 100) recruited from the outpatient clinic of our university hospital were compared with those of age- and sex-matched non-diabetic subjects (n = 50). The correlation of these urinary levels with the glycemic control and the clinical traits were examined. Furthermore, the influence of smoking habit on the levels of acrolein adduct was examined. Urinary levels of pentosidine, pyrraline and acrolein adduct were all significantly (p<0.001) higher in the DM group than in the non-DM group (pentosidine (log(pmol/mgCr)), 1.579 +/- 0.147 vs 1.427 +/- 0.142; pyrraline (log(nmol/mgCr)), 0.888 +/- 0.402 vs 0.581 +/- 0.336; acrolein adduct (log(nmol/mgCr)), 2.316 +/- 0.221 vs 2.051 +/- 0.201). Glycemic control parameters, such as fasting plasma glucose (FPG) and HbA1c, were significantly correlated with these urinary levels. Age was correlated with the urinary levels of pentosidine but not with those of pyrraline and acrolein adduct. The urinary albumin excretion rate did not correlate with any of these urinary levels. The levels of acrolein adduct were higher in the subjects with smoking habit than in those without the habit in the DM group as well as in the non-DM group (DM, 2.391 +/- 0.230 and 2.212 +/- 0.190, p=0.0004; Non-DM, 2.120 +/- 0.171 and 1.993 +/- 0.206, p=0.0503). The urinary levels of pentosidine, pyrraline and acrolein adduct were increased in DM and were significantly correlated with glycemic control levels. In addition, smoking habit seems to increase the urinary levels of acrolein adduct.     

Chondromodulin-I and its related gene Tenomodulin

During endochondral bone formation, vascular invasion into the cartilaginous rudiments triggers the subsequent replacement of cartilage by bone. We have found that the cartilage-derived glycoprotein, Chondromodulin- I (ChM- I ), is involved in the anti-angiogenic property of cartilage, and that its absence creates a permissive microenvironment for vascular invasion in cartilage. Recently, we reported that a novel ChM- I related molecule, Tenomodulin (TeM), is specifically expressed in tendon, epimysium, ligaments, sclera, and cornea, all of which are hypovascular or avascular. In contrast to ChM- I that is secreted and accumulates in the extracellular matrix, TeM is expressed on the cell surface as a type II transmembrane protein. Anti-angiogenic properties of TeM and ChM- I in mesenchyme will be reviewed.     

The adenomatous polyposis coli gene and human cancers

The APC (adenomatous polyposis coli) gene was isolated as a gene responsible for familial polyposis coli, an autosomal-dominant disease, characterized by development of hundreds to thousands of adenomatous polyps in the colon and rectum. However, recent studies revealed that inactivation of the APC gene also plays a significant role in development of sporadic forms of colorectal adenoma and carcinoma. Furthermore, somatic mutations have also been detected in pancreatic carcinomas as well as some type of gastric carcinomas, suggesting that APC has a critical function in regulation of cell growth in digestive tissues.     

Integration of hepatitis B virus DNA into cells of six established human hepatocellular carcinoma cell lines.

The authors successfully established 5 hepatocellular carcinoma cell lines, JHH-1, 2, 4, 5 and 6, derived from hepatitis B surface antigen seronegative patients and one line. JHH-7, from a patient considered to be a hepatitis B virus carrier. In the culture media of any of the JHH cell lines, including JHH-7, hepatitis B surface antigen was not detected by radioimmunoassay. However, in JHH-7, integration of hepatitis B virus DNA was confirmed at two sites on the chromosomes of this line by Southern blot hybridization. In contrast, in other JHH cell lines derived from hepatitis B surface antigen seronegative patients, integration of hepatitis B virus DNA into the chromosomes of cells was not detected. These cell lines will be useful in the investigation of hepatocellular carcinoma development, especially for research into non-A/non-B hepatitis viruses.     

New Diabetes Diagnostic Threshold of Hemoglobin A1c and the 3-Year Incidence of Retinopathy

The new diagnostic threshold of hemoglobin A_1c was made based on evidence from cross-sectional studies, and no longitudinal study supports its validity. To examine whether hemoglobin A_1c of 6.5% or higher defines a threshold for elevated risk of incident retinopathy, we analyzed longitudinal data of 19,897 Japanese adults who underwent a health checkup in 2006 and were followed up 3 years later. We used logistic regression models and restricted cubic spline models to examine the relationship between baseline hemoglobin A_1c levels and the prevalence and the 3-year incidence of retinopathy. The restricted cubic spline model indicated a possible threshold for the risk of incident retinopathy at hemoglobin A_1c levels of 6.0–7.0%. Logistic regression analysis found that individuals with hemoglobin A_1c levels of 6.5–6.9% were at significantly higher risk of developing retinopathy at 3 years compared with those with hemoglobin A_1c levels of 5.0–5.4% (adjusted odds ratio, 2.35 [95% CI 1.08–5.11]). Those with hemoglobin A_1c levels between 5.5 and 6.4% exhibited no evidence of elevated risks. We did not observe a threshold in the analysis of prevalent retinopathy. Our longitudinal results support the validity of the new hemoglobin A_1c threshold of 6.5% or higher for diagnosing diabetes.Diabetes is an increasingly important global public health concern (1). An estimated 285 million people, or 6.4% of the world’s population, lived with diabetes in 2010, and the number is expected to grow to 438 million by 2030 (1). In the U.S., 8.3% of children and adults are living with diabetes (2); likewise, in Japan, 7.8% of the population has diabetes (3).Recently, the International Expert Committee suggested use of a hemoglobin A_1c (HbA_1c) level of 6.5% or higher as the threshold for diagnosing diabetes (4,5). This criterion was subsequently adopted by the American Diabetes Association, European Association for the Study of Diabetes, and World Health Organization (4,5). In making its decision, the expert panel was informed by evidence from several cross-sectional studies that showed the association between HbA_1c level and the prevalence of retinopathy (4–12). The outcome of retinopathy has been historically accepted as the best criterion for comparing glycemic measures among several complications of diabetes (13,5), because it is a specific complication of diabetes that can be measured objectively (13,14). Few longitudinal studies have examined the association between HbA_1c levels and the risk of retinopathy in the general population, and these studies do not support the validity of this new diagnostic threshold (6,15–17). Many of the previous studies did not adjust for independent risk factors and confounders for retinopathy, such as age and hypertension.To examine the validity of the new HbA_1c thresholds, we tested the hypothesis that HbA_1c level of 6.5% or higher would define a threshold for increased 3-year incidence of retinopathy in a large cohort of Japanese adults.     

Initial clinical experience of early cardiac rehabilitation for very elderly patients over 85 years old following open heart surgery

In this study, we evaluated the initial clinical experience of early cardiac rehabilitation( CR) for very elderly patients over 85 years old after open heart surgery. From September 2007 to January 2011, 7 consecutive patients (85~90 years, mean 85.9 years, male:female=4:3) who underwent cardiac surgery in our institute were selected. Preoperative activity of daily living (ADL) scores were similar in all cases, and 1 patient used a cane for walking. Preoperative New York Heart Association (NYHA) classification was class III :3, class IV:4. Three patients were admitted for acute congestive heart failure approximately 1 month prior to surgery. Standard open heart surgery using bioprosthesis was performed: 3 patients underwent mitral valve replacement( MVR), 3 had aortic valve replacement( AVR), and 1 had tricuspid valve replacement (TVR). Postoperative clinical course was uneventful, and the mean time of ventilator support was 12.1 hours. Thereafter, early CR was introduced at the intensive care unit( ICU) in all patients, and the mean time of introduction of early rehabilitation was 1.7 days. In the last 4 cases, early CR was done the 1st day following surgery. CR was effectively performed in all cases without any problems or cardiac events, and all patients improved enough to leave their beds at 3~7 days, a mean of 4.4 days after surgery. The mean hospital stay after surgery was 30.9 days( 23 ~ 42 days), almost all patients were able to walk independently, and ADL scores at discharge were improved. Only 2 patients required a cane for walking. Postoperative NYHA classification was improved to class I :5, class II :2. From these results, early CR for very elderly patients over 85 years old could be a safe and effective tool to improve and maintain the ADL and quality of life following surgical intervention.