Six-month multicentric, open-label, randomized trial of twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11)

To evaluate glycemic control using convenience-oriented biphasic insulin analog compared with intensified insulin therapy, we conducted a 6-month multicentric, open-label, randomized trial in Japanese insulin-naive patients with type 2 diabetes mellitus. A total of 160 adult patients at 19 centers were randomized into two groups: those who received twice-daily injections of biphasic insulin aspart 30 and those on three-times-daily injections of insulin aspart with or without NPH insulin (multiple daily injections). At 6 months, mean HbA(1c) decreased by approximately 2.5% in both groups. Reduction of HbA(1c) on both regimens was better in patients whose prior therapy before starting the study was only diet and exercise (-5.0%) than in patients who were previously taking oral antidiabetic agents (-1.0%). No incidence of major hypoglycemia was observed in either regimen. These results suggest that convenience-oriented insulin therapy using biphasic insulin analog is as useful as intensified insulin therapy with insulin analog for the treatment of type 2 diabetes mellitus over 6 months. Furthermore, early induction of insulin therapy in individuals hitherto using only diet and exercise may provide good glycemic control. This study suggests that convenience-oriented biphasic insulin aspart 30 might be a useful option for the treatment of type 2 diabetes mellitus, especially for insulin-naive patients over 6 months, although it should be changed to another regimen when expected efficacy is not obtained.     

Enhanced ferromagnetism of ZnO@Co/Ni hybrid core@shell nanowires grown by electrochemical deposition method

The hybrid structure of ZnO NWs with the presence of different dopants recently has drawn many interests from researchers due to the possibility to integrate multiple functionalities into one single structure. In this article, we investigated the morphology, crystal structure and ferromagnetism of the ZnO@Co/Ni hybrid core@shell NWs prepared by a facile electrochemical deposition method. The results show that a thin layer of Ni and Co coated on the surface of ZnO NWs (confirmed by XRD, EDS, TEM and Raman scattering) can create a significant improvement of ferromagnetic property in such hybrid core@shell NWs. In which, for the coating time of 10, 15, 20 min, the value of M_s is around 0.67, 0.88 and 2.56 emu g⁻¹ for ZnO@Co NWs, and about 0.013, 0.022 and 0.031 emu g⁻¹ for ZnO@Ni NWs, respectively, in comparison with the number of 0.016 emu g⁻¹ for pure ZnO NWs. Interestingly, we also found the temperature dependence of ferromagnetism of such Co/Ni coated ZnO NWs. These results reveal the possibility to employ such hybrid core@shell NWs for many applications, e.g. spin field effect transistors.

Facile electrochemical synthesis of ZnO@Co and ZnO@Ni hybrid core@shell nanowires with enhanced ferromagnetism.     

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.     

Quantitative evaluation of the pulmonary microdistribution of TiO2 nanoparticles using X‐ray fluorescence microscopy after intratracheal administration with a microsprayer in rats

The unevenness of pulmonary nanoparticle (NP) distribution, which hinders the establishment of an absolute dose–response relationship, has been described as one of the limitations of intratracheal administration techniques for toxicological assessment of inhaled NPs. Quantification of the NP microdistribution would facilitate the establishment of a concentration–response relationship in localized regions of the lung; however, such quantitative methods have not been reported. Here, we established a quantitative method for evaluating pulmonary TiO₂ NP microdistribution in rats using X‐ray fluorescence microscopy. Ti intensity in lung sections from rats intratracheally administered 10 mg kg^–1 TiO₂ NPs with a microsprayer was measured using X‐ray fluorescence with a 100 µm beam size. Ti reference samples were prepared by dropping different concentrations of Ti solutions on glass slide or lung sections of untreated rat. Ti intensity increased linearly with Ti content in the reference samples on both substrates. The detection limit of TiO₂ was estimated to be 6.3 ng mm^–2. The reproducibility was confirmed for measurements done in the short‐ (2 weeks) and long‐term (6 months). The quantitative results of TiO₂ NP microdistribution suggested that more TiO₂ NPs were distributed in the right caudal and accessory lobes, which are located downstream of the administration direction of the NP suspension, and the lower portion of each lobe. The detection rates of TiO₂ NPs were 16.6–25.0%, 5.19–15.6%, 28.6–39.2%, 21.4–38.7% and 10.6–23.2% for lung sections from the right cranial, middle, caudal, accessory and left lobes, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

Nationwide epidemiological survey of patients with idiopathic interstitial pneumonias using clinical personal records]

A nationwide epidemiological survey of idiopathic interstitial pneumonias (IIPs) in 2005 was performed using clinical personal records. According to the data from the Japan Intractable Diseases Information Center, 4,396 patients with IIPs were covered by public insurance. The prevalence of IIPs in Japan was estimated to be 3.44 per 100,000. The forms of 1543 patients (new: 658, recurrent: 885) were collected. Of 1543 cases, 1322 cases (85.7%) had idiopathic pulmonary fibrosis (IPF), therefore details were investigated in patients with IPF. The mean age at onset was 65.4 years and men were more frequent than women (878 in men, 444 in women). The severity, diagnostic method, symptoms, imaging findings, and pulmonary function tests were analyzed in the new forms. Severity levels of I, II, III and IV were seen in 32, 28, 177, and 287 cases, respectively. A pathological diagnosis was made in 67 cases (12%). The positive rates of fine crackles, dry cough, exertional dyspnea, and finger clubbing were 98%, 94%, 98%, and 53%, respectively. On HRCT, honeycomb was noted in the subpleural lung lesions in more than 90% of the cases. As for pulmonary function tests, restrictive and diffusing capacity impairment were noted in 86% and 92%, respectively, and SpO2 was below than 90% in 91% on a 6-minute walking test. The serum KL-6 level was elevated in 95%. Most of the IPF analyzed cases were at a severity level of III or IV because the analysis aimed at those coverage by public insurance. Since this was only the initial nationwide epidemiological survey in Japan, the current situation should be investigated.     

Lowering of oxidative stress in hemodialysis patients by dialysate cleaning: in relation to arteriosclerosis

The objective of this study was to investigate changes in oxidative stress associated with the cleaning of the dialysate. Thirty-six dialysis patients were studied. Changes in soluble CD-14 (sCD-14), malondialdehyde-low-density lipoprotein (MDA-LDL), and oxidized-LDL (Ox-LDL) were monitored for 1 year before and 1 year after dialysate cleaning. The mean endotoxin (ET) level in the dialysate had previously been confirmed to decrease from 39.0 EU/L to an undetectable level after the cleaning. The mean levels of sCD-14, MDA-LDL, and Ox-LDL decreased significantly after the cleaning (sCD-14, P < 0.0001; MDA-LDL, P < 0.001; Ox-LDL, P < 0.001). One year after the cleaning, six cases still showed high levels of MDA-LDL and Ox-LDL. Cardiovascular events occurred in four of those six cases within 2.8 years after the cleaning. These four patients suffered from strong oxidative stress during dialysis, even after the cleaning. We therefore concluded that high levels of MDA-LDL and Ox-LDL are improved in dialysis patients by cleaning of the dialysate. These results indicate that even a dialysate containing 50 EU/L or less ET may stimulate monocytes and cause oxidative stress. They also suggest that even low levels of ET may aggravate arteriosclerosis in dialysis patients. Thus, in order to prevent cardiovascular events in dialysis patients, it is necessary to purify the dialysate.     

A case of pulmonary squamous cell carcinoma coexisting with pulmonary actinomycosis]

A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis.