Tumor necrosis factor α (TNFα) induces pro-matrix metalloproteinase 9 production in human uterine cervical fibroblasts but interleukin 1 α antagonizes the inductive effect of TNFα

AbstractWe have examined the regulation of precursor of matrix metalloproteinase 9 (proMMP-9)/progelatinase B production by tumor necrosis factor α (TNFα) and interleukin 1α (IL-1α) using human uterine cervical fibroblasts. TNFα, but not IL-1α, induces the production of proMMP-9 in the cervical cells. IL-1α, however, suppresses the TNFα-induced proMMP-9 production. 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulates the cervical cells to produce proMMP-9, and IL-1α synergistically enhances its production. TNFα-induced proMMP-9 production is not mediated by protein kinase C (PKC), whereas the effect of IL-1α is through PKC. By contrast, proMMP-3/prostromelysin 1 is up-regulated by TNFα or TPA in the presence of IL-1α, whose modulation is PKC-dependent. The suppressive effect of IL-1α on the TNFα-induced proMMP-9 production is a new biological effect of IL-1 on MMP production

Aortic stiffness is strikingly increased with age ≥50 years in clinically normal individuals and preclinical patients with cardiovascular risk factors: Assessment by the new technique of 2D strain echocardiography

SummaryBackgroundVarious measures of aortic stiffness have been proposed as cardiovascular risk markers, but interest has now shifted to more direct and easier evaluation of aortic function. The present study was conducted to determine the feasibility of measuring aortic stiffness (β) with two-dimensional (2D) strain echocardiography and the impact of age and gender on preclinical atherosclerosis.Methods and resultsThe peak circumferential strain of the abdominal aorta was measured using 2D strain echocardiography, and β was determined in 54 clinically normal individuals and 104 patients with cardiovascular risk factors and no evidence of cardiovascular disease. The β correlated significantly with age in all 158 patients. However, the relationship was nonlinear, and β was markedly greater in patients ≥50 years. In 54 clinically normal individuals, the relationship was comparatively linear. The systolic blood pressure and pulse pressure were significantly greater in patients ≥50 years. There were no significant differences in β and blood pressure parameters between genders.ConclusionsThe β increased dramatically with advanced age (≥50 years), regardless of gender, in clinically healthy and community-based patients with cardiovascular risk factors. The aortic circumferential strain was measured with 2D strain echocardiography which is a new tool that can be used to directly and easily evaluate aortic stiffness

Haemodynamic Changes in the Superior Mesenteric Artery Induced by Acupuncture Stimulation on the Lower Limbs

Acupuncture is commonly performed on acupoints. A comparison of quantitative physiological alterations induced by stimulation on different acupoints has never been performed in the superior mesenteric artery (SMA) in humans. Therefore, we investigated changes in blood flow volume (BFV) in the SMA as an indicator of physiological effects induced by stimulation on 3 points. Thirty healthy participants aged 29 ± 10 years (mean ± SD) were enrolled. All participants underwent stimulations on 3 points located in the lower legs: ST36, LR3, and a non-acupoint. Control pertains to a condition with no-stimulation. Stimulation was performed bilaterally with manual rotation of the needles. BFV was measured by ultrasonography before insertion and 10, 20, 30, and 60 minutes after stimulation. Following acupuncture on ST36, BFV increased significantly 20 and 30 minutes after stimulation, compared to BFV before insertion (P < 0.05). Following stimulation on LR3 and the non-acupoint, no significant differences in BFV could be found. Relative to the no-stimulation group, stimulation on LR3, and the non-acupoint, stimulation on ST36 elicited a significant increase in BFV (P < 0.05). The results suggest that stimulation on the different points causes distinct physiological effects in BFV in the SMA

Metallic phase in the metal-intercalated higher fullerene Rb8.8(7)C84

A new material of higher fullerene, RbxC84, was synthesized by intercalating Rb metal into C-84 crystals. The RbxC(84) crystals showed a simple cubic (sc) structure with lattice constant, a, of 16.82 (2) angstrom at 6.5 K, and 16.87 (2) angstrom at 295 K. The Rietveld refinements were achieved with the space group, Pa (3) over bar, based on a model that the C-2 axis of D2d-C84 aligned along [111]. The sample composition was determined to be Rb-8.8(7) C-84. The ESR spectrum at 303 K was composed of a broad peak with peak-to-peak linewidth Delta H-pp of 220 G, and a narrow peak with Delta H-pp of 24 G. Temperature dependence of the broad peak clearly showed a metallic behavior. The metallic behavior was discussed based on a theoretical calculation. This finding of new metallic phase in a higher fullerene is the first step for a development of new types of fullerene materials with novel physical properties such as superconductivity.</p

Quinazolinobenzodiazepine Derivatives, Novobenzomalvins A–C: Fibronectin Expression Regulators from Aspergillus novofumigatus

Three new quinazolinobenzodiazepine derivatives, novobenzomalvins A (1), B (2), and C (3), have been isolated as fibronectin expression regulators from Aspergillus novofumigatus CBS117520. The structures of 1 to 3 were established by spectroscopic and physicochemical analysis, and chemical investigation including the total synthesis of 1. Treatment with novo-benzomalvins A (1), B (2), C (3), and N-methylnovobenzomalvin A (5) increased the expression of fibronectin in normal human neonatal dermal fibroblast cells

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

医薬保健研究域薬学系The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market. Copyright © 2018 by The American Society of Tropical Medicine and Hygiene