Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects >75 years of age

Levels of lipoprotein (a) (Lp[a]) and various hemostatic factors were studied in 132 Japanese aged >75 years (mean 83). The group consisted of 50 healthy persons, 36 hypertensive subjects, 31 patients with chronic cerebral infarction, and 15 with coronary artery disease. Lp(a) levels were slightly lower in the healthy “old old” subjects than in the 184 healthy younger adults (mean ± SD: 10.7 ± 7.9 vs 12.1 ± 10.1 mg/dl). There were no gender-related differences in the Lp(a) levels of healthy adults and healthy old old subjects. Lp(a) levels were higher in the hypertensive old old subjects (14.6 ± 15.4 mg/dl) and the old old patients with cerebral infarction (21.3 ± 16.2 mg/dl) and coronary artery disease (26.5 ± 20.4 mg/dl). The prevalence of subjects with high Lp(a) levels (>30 mg/dl) was the greatest among old old patients with coronary artery disease (27%). Lp(a) levels in the 132 old old subjects showed positive correlations with sialic acid, fibrinogen, factor VII activity, and D-dimer levels. These results indicate a close association between Lp(a) levels and atherothrombotic disease as well as the characteristics of Lp(a) as an acute phase reactant in old old Japanese. Subjects with higher Lp(a) levels may develop cardiovascular disease later in life, whereas the remaining healthy old old subjects have lower Lp(a) levels.     

Cutoff value of 1 h, 50 g glucose challenge test for screening of gestational diabetes mellitus in a Japanese population

A total of 2651 consecutive native Japanese women who underwent a glucose challenge test (GCT) were retrospectively investigated. GCT was performed between 24 and 27 weeks of gestation; each subject received a 50 g oral glucose load without regard to the fasting or fed state, followed by a determination of 1 h venous plasma glucose level. Women demonstrating GCT exceeding 130 mg/dl received a 75 g, 2 h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus (GDM). All women with GDM were treated with a strict diabetic protocol including insulin therapy. Forty-nine (1.8%) women were diagnosed to have GDM. The receiver-operator characteristic curve identified a GCT finding above 140 mg/dl as the cutoff value for detecting GDM, which showed a sensitivity and specificity of 96 and 76%, respectively. Our results suggest that the cutoff value of a 50 g GCT is 140 mg/dl to identify pregnancies with GDM in a Japanese population.     

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.A long-term goal in contemporary cancer nanomedicine has been to design and generate drug delivery systems that improve the narrow therapeutic window associated with conventional chemotherapeutics (1, 2). Conceptually, several nanotechnology-based entity candidates, including protocells (3), biosynthetic nanoparticles (NPs), viruses, and liposome-based nanoparticles, could be targeted for active delivery through a defined cell surface ligand receptor system and/or physically triggered for finely tuned cargo release (2, 4, 5).Numerous efforts have been made to functionalize NPs by combining them with antibodies, aptamers, peptides, vitamins, or carbohydrates (6–8), but the majority of studies involve untargeted nanoplatforms (4, 9). In practice, targeting NPs is far from trivial, and ongoing challenges include synthesis and purification, selection of an appropriate ligand receptor, and specific composition for NP conjugation. Even the conjugation reaction itself may alter the binding of the tumor-targeting moiety to its receptor through conformational changes, steric freedom restriction, or orientation distortion (10, 11). Unfortunately, the cost-to-benefit ratio of these modifications often elevate the complexity of the NP synthesis, complicating regulatory hurdles because of formulations that are heterogeneous or difficult to reproduce (10, 12, 13).To minimize such drawbacks, NPs can be functionalized via virus-based nanoplatforms as an alternative for targeted cargo delivery (14–16). In particular, filamentous bacteriophage (phage)—a prokaryotic virus—is an attractive candidate to develop a bionanomedicine for cancer therapeutics because phage particles are cost-effectively produced with biological uniformity, as well as being physically robust and stable under harsh conditions (17). Notably, phage-based nanoplatforms are biocompatible and nonpathogenic with eukaryotic organisms and are able to preserve the desired cell targeting and internalization (18). Moreover, phage particles are ideal for incorporating other NPs, which can be released after reaching the tumor site. An admixture of colloidal gold NP (AuNP) with phage particles spontaneously organizes into hydrogel network-like fractal structures (19, 20). These hydrogel networks offer convenient multifunctional integration within a single entity for tumor targeting, enhanced fluorescence and dark-field microscopy, near-infrared (NIR) photon-to-heat conversion, and surface-enhanced Raman scattering (SERS)-based detection (20, 21).In the present work, we developed a tumor targeting theranostic (meaning a combination of therapeutics and diagnostics) hydrogel-based nanoplatform that enables ligand-directed tumor targeting, multimodal imaging capability, and triggered therapeutic cargo release. Our data suggest that targeted hydrogel photothermal therapy represents a functional theranostic approach (fostering “see and treat, treat and see”) in the diagnosis and management of tumors.     

Relationship between paraspinal muscle cross-sectional area and relative proprioceptive weighting ratio of older persons with lumbar spondylosis

[Purpose] The purpose of this study was to examine the relationship between the paraspinal muscle cross-sectional area and the relative proprioceptive weighting ratio during local vibratory stimulation of older persons with lumbar spondylosis in an upright position. [Subjects] In all, 74 older persons hospitalized for lumbar spondylosis were included. [Methods] We measured the relative proprioceptive weighting ratio of postural sway using a Wii board while vibratory stimulations of 30, 60, or 240 Hz were applied to the subjects’ paraspinal or gastrocnemius muscles. Back strength, abdominal muscle strength, and erector spinae muscle (L1/L2, L4/L5) and lumbar multifidus (L1/L2, L4/L5) cross-sectional areas were evaluated. [Results] The erector spinae muscle (L1/L2) cross-sectional area was associated with the relative proprioceptive weighting ratio during 60Hz stimulation. [Conclusion] These findings show that the relative proprioceptive weighting ratio compared to the erector spinae muscle (L1/L2) cross-sectional area under 60Hz proprioceptive stimulation might be a good indicator of trunk proprioceptive sensitivity.Key words: Relative proprioceptive weighting ratio, Erector spinae muscle cross-sectional area, Older persons with lumbar spondylosis