Prevalence of subclinical atherosclerosis in asymptomatic diabetic patients by 64-slice computed tomography

OBJECTIVES: Patients with diabetes have a 2-fold to 4-fold higher risk of a cardiovascular event than nondiabetic patients. Thus there is a need to identify patients with diabetes who are at risk of cardiovascular events before the onset of symptoms. We studied the prevalence of coronary artery disease in asymptomatic diabetic patients compared with asymptomatic nondiabetic patients by 64-slice computed tomography (CT). METHODS: From 425 asymptomatic patients with coronary risk factors but without known coronary artery disease who underwent 64-slice CT, we identified 93 asymptomatic diabetic patients (diabetic group) and 93 age-matched and sex-matched asymptomatic nondiabetic patients. RESULTS: Clinical characteristics were not significantly different between the two groups. Total coronary calcium score was significantly higher in diabetic group than that in nondiabetic group (median 117 vs. 53.5, P<0.0001). No coronary calcium was detected in 30.0% of nondiabetic group compared with 15.1% of diabetic group (P=0.0022). Coronary calcium score more than 400 was detected in 9.7% of nondiabetic group compared with 36.6% of diabetic group (P<0.0001). Coronary plaques were found in 67.7% of nondiabetic group compared with 91.4% of diabetic group (P<0.0001). Multiple plaques were detected in 57.0 and 77.4% of patients in nondiabetic and diabetic group, respectively (P=0.0030). Significant coronary stenosis was found in 16.1% of nondiabetic group compared with 33.3% of diabetic group (P=0.0065). CONCLUSION: Our results show that the prevalence of coronary plaques detectable by 64-slice CT in asymptomatic diabetic patients is very high.     

Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments

To reveal the involvement of extracellular nucleotides in the ossification process in ossification of the posterior longitudinal ligament of the spine (OPLL), the mRNA expression profiles of P2 purinoceptors, mechanical stress-induced ATP release, and ATP-stimulated expression of osteogenic genes were analyzed in ligament cells derived from the spinal ligament of OPLL patients (OPLL cells) and non-OPLL cells derived from the spinal ligaments of cervical spondylotic myelopathy patients as a control. The extracellular ATP concentrations of OPLL cells in static culture were significantly higher than those of non-OPLL cells, and this difference was diminished in the presence of ARL67156, an ecto-nuclease inhibitor. Cyclic stretch markedly increased the extracellular ATP concentrations of both cell types to almost the same level. P2Y1 purinoceptor subtypes were intensively expressed in OPLL cells, but only weakly expressed in non-OPLL cells. Not only ATP addition but also cyclic stretch raised the mRNA levels of alkaline phosphatase and osteopontin in OPLL cells, which were blocked by MRS2179, a selective P2Y1 antagonist. These increases in the expression of osteogenic genes were not observed in non-OPLL cells. These results suggest an important role of P2Y1 and extracellular ATP in the progression of OPLL stimulated by mechanical stress.     

Measurement of human blood viscosity by an electromagnetic spinning sphere viscometer

We herein applied an electromagnetic spinning sphere (EMS) viscometer to the measurement of human blood viscosity for the first time. We collected blood samples from 100 healthy outpatient volunteers in order to analyse viscosity dependence on blood cell parameters and on the shear rate with a simple approximation formula [η_i (γ)\, = A_i γ^{- pi} + η₀]. Viscosity dependence on blood cell parameters was relatively high at a high shear rate, but became lower as the shear rate decreased. The approximation formula with appropriate parameters of A_i and p_i nearly faithfully reproduced actual blood rheological behaviour with a standard deviation of 1.5%. The distributions of A_i and p_i values were broad, suggesting that the pattern of viscosity dependence on the shear rate varied with individual differences. The results obtained using the EMS viscometer suggest that blood viscosity values are individual-specific and actual individual measurements are important for understanding rheological conditions.     

Catalase expression of Propionibacterium acnes may contribute to intracellular persistence of the bacterium in sinus macrophages of lymph nodes affected by sarcoidosis

Immunologic Research - Bacterial catalase is important for intracellular survival of the bacteria. This protein of Propionibacterium acnes, one of possible causes of sarcoidosis, induces...     

High‐Performance Polybenzoxazine Derived from Polyfunctional Benzoxazine Composed of an Oligonuclear Phenolic Compound Having a 4,4′‐Dimethylenebiphenyl Linker

A novel polyfunctional benzoxazine monomer, OP‐a , is synthesized from aniline, formaldehyde, and an oligonuclear phenolic compound (OP) with a 4,4′‐dimethylenebiphenyl group as the phenol linker. After thermal curing of OP‐a up to 240 °C, a brown‐colored, transparent polybenzoxazine ( POP‐a ) film is obtained. The mechanical and thermal properties of the POP‐a film are investigated by tensile test, dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). The POP‐a film is extremely tough compared with a typical polybenzoxazine ( PB‐a ) film. The elongation at break of the POP‐a film is 7.6%, which is surprisingly large for the highly cross‐linked thermoset. The high cross‐link density is suggested from the very high storage modulus (over 1 GPa) above the glass transition temperature (T _g) observed by DMA. The T _g of POP‐a is also improved significantly to T _g = 223 °C, which is approximately 50 °C higher than that of PB‐a . Moreover, TGA reveals that the thermal stability of POP‐a is also enhanced.     

3D Printing of Tough Gels Having Tunable Elastic Modulus from the Same Pre‐Gel Solution

A gel forming method with sections with different elastic modulus is developed. Gels with hardness distribution are formed from one base gel material by adjusting the crosslinking density of the polymer network using a 3D gel printer. It is confirmed that hardness is arranged as designed by using mixing rules of composite materials. Furthermore, as a prototype of a practical gel application, a gel finger model having a soft‐fleshy part and a hard‐bony part is printed. 3D printing of an organ model that reproduces a realistic feel that takes not only the shape of the organ but also the distribution of hardness into consideration may become possible.     

UCN-01 (7-Hydroxystaurosporine) Enhances 5-Fluorouracil Cytotoxicity through Down-regulation of Thymidylate Synthetase Messenger RNA

UCN-01 (7-hydroxystaurosporine) is a newly developed cell cycle inhibitor known to have several modes of action, including inhibition of cyclin-dependent kinase, induction of p21 and suppression of pRb phosphorylation. In order to test a combination therapy of UCN-01 and 5-fluorouracil (5-FU), growth inhibition of CRL 1420 (MIA PaCa-2; undifferentiated pancreatic carcinoma) by four different treatments was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The treatments used were UCN-01 alone, 5-FU alone, 5-FU followed by UCN-01 (5-FU/UCN-01) and UCN-01 followed by 5-FU (UCN-01/5-FU). We also assessed changes in thymidylate synthetase (TS) mRNA levels, TS activity, and 5-FU incorporation by RNA (FRNA) for each treatment. Although treatment with UCN-01 alone, 5-FU alone, and 5-FU/UCN-01 inhibited CRL 1420 growth in a concentration-dependent manner, treatment with UCN-01/5-FU inhibited the growth of CRL 1420 synergistically at less than 1 μg/ml drug concentration. The down-regulation of TS mRNA by UCN-01 resulted in stable total TS and decreased free TS, and UCN-01/5-FU resulted in enhanced thymidylate synthetase inhibition rate (TSIR) compared to UCN-01 alone and 5-FU/UCN-01. This increased TSIR due to UCN-01 pretreatment was accompanied by elevated F-RNA concentrations in the UCN-01/5-FU treatment. The suppression of TS mRNA and TS activity by UCN-01 may lead to higher sensitivity of tumor cells to 5-FU and may explain the synergistic antitumor effect of UCN-01/5-FU. In conclusion, low concentrations of UCN-01 (from 0.01 to 1 μg/ml) may be clinically useful, affording low cytotoxicity of UCN-01, while enhancing the antitumor effect of 5-FU.