Mid-infrared laser heterodyne spectrometer by hollow optical fiber and its newly designed coupler.

We demonstrate a newly designed, to the best of our knowledge, hollow optical fiber coupler for a mid-infrared (IR) laser heterodyne spectrometer that mixes a targeted light source with local oscillator (LO) light. The hollow fiber achieves a high transmission efficiency ∼80-90%/m, not only for a coherent laser source but also for an incoherent blackbody source. The branching characteristics of the hollow optical fiber coupler are found to be strongly dependent on the curvature and length of the input port fiber, indicating that the branching ratio could be designed independently for each input port. Our laboratory measurements demonstrate that the branching ratio and transmittance of the coupler can be varied by coupling a flexible fiber to the input side owing to the excitation of higher-order modes. Using the hollow optical fiber coupler, a high-resolution emission spectrum of the quantum cascade laser at 10.3 µm for our C O 2 laser-based heterodyne spectrometer is successfully achieved. Using a C O 2 laser with a hollow fiber and a blackbody as a direct input signal in free space, we obtain the sensitivity performance of IR laser heterodyne spectrometer as 2000-3000 K of the system noise temperature. This suggests that the transmission of a coherent LO laser through a hollow optical fiber has almost the same sensitivity for the IR heterodyne detection as that without a fiber.

Prognostic potential and pathological validation of a diagnostic application using Raman spectroscopy in the characterization of degenerative changes in the cartilage of the humeral head.

Significance: Raman spectroscopy is a well-established analytical method in the fields of chemistry, industry, biology, pharmaceutics, and medicine. Previous studies have investigated optical imaging and Raman spectroscopy for osteoarthritis (OA) diagnosis in weight-bearing joints such as hip and knee joints. However, to realize early diagnosis or a curable treatment, it is still challenging to understand the correlations with intrinsic factors or patients' background. Aim: To elucidate the correlation between the Raman spectral features and pathological variations of human shoulder joint cartilage. Approach: Osteoarthritic cartilage specimens excised from the humeral heads of 14 patients who underwent shoulder arthroplasty were assessed by a confocal Raman microscope and histological staining. The Raman spectroscopic dataset of degenerative cartilage was further analyzed by principal component analysis and hierarchical cluster analysis. Results: Multivariate association of the Raman spectral data generated three major clusters. The first cluster of patients shows a relatively high Raman intensity of collagen. The second cluster displays relatively low Raman intensities of proteoglycans (PGs) and glycosaminoglycans (GAGs), whereas the third cluster shows relatively high Raman intensities of PGs and GAGs. The reduced PGs and GAGs are typical changes in OA cartilage, which have been confirmed by safranin­O staining. In contrast, the increased Raman intensities of collagen, PGs, and GAGs may reflect the instability of the cartilage matrix structure in OA patients. Conclusions: The results obtained confirm the correlation between the Raman spectral features and pathological variations of human shoulder joint cartilage. Unsupervised machine learning methods successfully yielded a clinically meaningful classification between the shoulder OA patients. This approach not only has potential to confirm severity of cartilage defects but also to determine the origin of an individual's OA by evaluating the cartilage quality.

A 52-week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N-ISM study.

AIM: To compare the long-term efficacy of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors as second-line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD). MATERIALS AND METHODS: In a 52-week randomized open-label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks. RESULTS: Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2 , 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C-peptide and high-density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11). CONCLUSION: The HbA1c-lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.

Infrared Hollow Optical Fiber Probe for Localized Carbon Dioxide Measurement in Respiratory Tracts.

A real-time gas monitoring system based on optical absorption spectroscopy is proposed for localized carbon dioxide (CO2) measurement in respiratory tracts. In this system, a small gas cell is attached to the end of a hollow optical fiber that delivers mid-infrared light with small transmission loss. The diameters of the fiber and the gas cell are smaller than 1.2 mm so that the probe can be inserted into a working channel of common bronchoscopes. The dimensions of the gas cell are designed based on absorption spectra of CO2 standard gases in the 4.2 µm wavelength region, which are measured using a Fourier-transform infrared spectrometer. A miniature gas cell that is comprised of a stainless-steel tube with slots for gas inlet and a micro-mirror is fabricated. A compact probing system with a quantum cascade laser (QCL) light source is built using a gas cell with a hollow optical fiber for monitoring CO2 concentration. Experimental results using human breaths show the feasibility of the system for in-situ measurement of localized CO2 concentration in human airways.

Real-Time Analysis of Isoprene in Breath by Using Ultraviolet-Absorption Spectroscopy with a Hollow Optical Fiber Gas Cell.

A breath analysis system based on ultraviolet-absorption spectroscopy was developed by using a hollow optical fiber as a gas cell for real-time monitoring of isoprene in breath. The hollow optical fiber functions as an ultra-small-volume gas cell with a long path. The measurement sensitivity of the system was evaluated by using nitric-oxide gas as a gas sample. The evaluation result showed that the developed system, using a laser-driven, high-intensity light source and a 3-m-long, aluminum-coated hollow optical fiber, could successfully measure nitric-oxide gas with a 50 ppb concentration. An absorption spectrum of a breath sample in the wavelength region of around 200-300 nm was measured, and the measured spectrum revealed the main absorbing components in breath as water vapor, isoprene, and ozone converted from oxygen by radiation of ultraviolet light. The concentration of isoprene in breath was estimated by multiple linear regression. The regression analysis results showed that the proposed analysis system enables real-time monitoring of isoprene during the exhaling of breath. Accordingly, it is suitable for measuring the circadian variation of isoprene.

Multi-element hollow-core anti-resonant fiber for infrared thermal imaging.

A bundle composed of 245 anti-resonant glass hollow optical fibers with a total diameter of 1 mm and fiber core diameter of 60 µm is fabricated for endoscopic infrared-thermal imaging. The bundle fiber shows low losses in the wavelength range of 3 to 4 µm owing to the anti-resonant effect of the thin glass wall. An image resolution of around 420 µm with a field-of-view of 3-mm diameter is obtained although crosstalk between adjacent fibers is observed. The experimental results of an imaging system using the fiber bundle with a half-ball lens at the distal end, which can be inserted into a working channel of endoscopes, are also shown.

Hollow optical-fiber based infrared spectroscopy for measurement of blood glucose level by using multi-reflection prism.

A mid-infrared attenuated total reflection (ATR) spectroscopy system employing hollow optical fibers and a trapezoidal multi-reflection ATR prism has been developed to measure blood glucose levels. Using a multi-reflection prism brought about higher sensitivity, and the flat and wide contact surface of the prism resulted in higher measurement reproducibility. An analysis of in vivo measurements of human inner lip mucosa revealed clear signatures of glucose in the difference spectra between ones taken during the fasting state and ones taken after ingestion of glucose solutions. A calibration plot based on the absorption peak at 1155 cm(-1) that originates from the pyranose ring structure of glucose gave measurement errors less than 20%.

Infrared hollow optical fiber probes for reflectance spectral imaging.

Systems for infrared reflectance imaging are built with an FT-IR spectrometer, hollow optical fibers, and a high-speed infrared camera. To obtain reflectance images of biological samples, an optical fiber probe equipped with a light source at the distal end and a hybrid fiber probe composed of fibers for beam radiation and ones for image detection have been developed. By using these systems, reflectance spectral images of lipid painted on biomedical hard tissue, which provides reflectance of around 4%, are successfully acquired.

Elevated small dense low-density lipoprotein cholesterol as a predictor for future cardiovascular events in patients with stable coronary artery disease.

AIM: The aim of the present study was to investigate how small dense low-density lipoprotein cholesterol (sdLDL-C) compared with LDL-C affect the long-term prognosis in patients with stable coronary artery disease (CAD). METHODS: sdLDL-C measured by heparin magnesium precipitation and LDL particle size measured by non-denatured gradient-gel electrophoresis were compared in 190 consecutive CAD patients who underwent coronary arteriography between 2003 and 2004 who did or did not develop cardiovascular events during a seven-year follow-up period. Cardiovascular events were death caused by cardiovascular diseases(CVDs), onset of acute coronary syndrome, need for coronary and peripheral arterial revascularization, hospitalization for heart failure, surgical procedure for any CVDs, and/or hospitalization for stroke. RESULTS: First-time cardiovascular events were observed in 72 patients. Those who experienced cardiovascular events were older and had higher prevalence rates of hypertension and diabetes; significantly higher Gensini coronary atherosclerotic scores; significantly higher levels of sdLDL-C, sdLDL-C/LDL-C, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratios; and greater glycated hemoglobin(Hb)A1c and brain natriuretic peptide (BNP) levels. They also had significantly smaller LDL particle sizes, HDL-C, apolipoprotein A-1, and estimated glomerular filtration rate (GFR) compared with patients without cardiovascular events. Conversely, LDL-C, non-HDL-C, apolipoprotein B, remnantlike particle cholesterol, and high-sensitivity C-reactive protein (hs-CRP) levels were similar between the two groups. A Kaplan-Meyer event-free survival curve demonstrated that patients with sdLDL-C≥35 mg/dL (median level) had significantly poorer prognosis compared with those with lower sdLDL-C levels, while patients with LDL-C ≥100 mg/dL had a non-significantly lower survival rate. CONCLUSION: These results confirm that sdLDL-C is a very promising biomarker to predict future cardiovascular events in the secondary prevention of stable CAD.

IL-6 mobilizes bone marrow-derived cells to the vascular wall, resulting in neointima formation via inflammatory effects.

AIM: Among the many factors related to bone marrow cell mobilization, local inflammation induced by cytokines may drive bone marrow cells to the vascular wall, resulting in a thickened neointima. However, the relationship between inflammatory reactions and bone marrow cell invasion has not yet been fully clarified. METHODS: We inserted a large wire into the femoral artery in male balb/c(WT), interleukin (IL)-6-knockout (KO) and bone marrow-transplanted (BMT) mice that had received bone marrow cells from KO mice. Immunohistochemistry was performed to evaluate the degree of intimal hyperplasia and inflammation following vascular injury. RESULTS: Three days after the vascular injury, the number of CD34/Sca-1-positive cells in the blood was higher in the KO mice. The numbers of apoptotic cells in the neointima was lower in the KO and BMT mice at two hours after injury. The morphometric analysis performed at one and four weeks after injury showed that the intima/media ratio was significantly lower in the KO and BMT mice, while CD34-positive cells were much more frequent in the WT mice. Furthermore, re-endothelialization appeared earlier in the KO and BMT mice than in the WT mice. No differences in the levels of vascular endothelial growth factor or hepatocyte growth factor were observed in the mice sera between the WT, KO and BMT mice after injury. The in vitro culture of bone marrow cells showed more differentiated smooth muscle-like cells in the WT mice than in the KO mice. CONCLUSIONS: IL-6 is involved in neointimal formation following vascular injury, possibly acting through inflammatory effects inducing the production of bone marrow cells.

Remote Fourier transform-infrared spectral imaging system with hollow-optical fiber bundle.

A spectral imaging system consisting of a Fourier transform-infrared spectrometer, a high-speed infrared camera, and a bundle of hollow-optical fibers transmitting infrared radiation images was constructed. Infrared transmission spectra were obtained by carefully processing multiple interferograms taken by high-speed photography. Infrared spectral images of a variety of samples captured by the system were measured. We successfully detected existence maps of the oil and fat of biological samples by mapping the transmission of specific wavelengths in the spectrum.

Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization.

Few reports have examined the effects of adult bone marrow multipotent stromal cells (MSCs) on large animals, and no useful method has been established for MSC implantation. In this study, we investigate the effects of MSC infusion from the coronary vein in a swine model of chronic myocardial infarction (MI). MI was induced in domestic swine by placing beads in the left coronary artery. Bone marrow cells were aspirated and then cultured to isolate the MSCs. At 4 weeks after MI, MSCs labeled with dye (n=8) or vehicle (n=5) were infused retrogradely from the anterior interventricular vein without any complications. Left ventriculography (LVG) was performed just before and at 4 weeks after cell infusion. The ejection fraction (EF) assessed by LVG significantly decreased from baseline up to a follow-up at 4 weeks in the control group (P<0.05), whereas the cardiac function was preserved in the MSC group. The difference in the EF between baseline and follow-up was significantly greater in the MSC group than in the control group (P<0.05). The MSC administration significantly promoted neovascularization in the border areas compared with the controls (P<0.0005), though it had no affect on cardiac fibrosis. A few MSCs expressed von Willebrand factor in a differentiation assay, but none of them expressed troponin T. In quantitative gene expression analysis, basic fibroblast growth factor and vascular endothelial growth factor (VEGF) levels were significantly higher in the MSC-treated hearts than in the controls (P<0.05, respectively). Immunohistochemical staining revealed VEGF production in the engrafted MSCs. In vitro experiment demonstrated that MSCs significantly stimulated endothelial capillary network formation compared with the VEGF protein (P<0.0001). MSC infusion via the coronary vein prevented the progression of cardiac dysfunction in chronic MI. This favorable effect appeared to derive not from cell differentiation, but from enhanced neovascularization by angiogenic factors secreted from the MSCs.

Acute effects of intravenous nicorandil on hemodynamics in patients hospitalized with acute decompensated heart failure.

BACKGROUND: Nicorandil injection, a potent vasodilator with K(ATP) channel opening action and nitrate-like action, has been used for treatment of unstable angina. In the present investigation, we examined the effect of intravenous nicorandil on hemodynamics in patients with acute decompensated heart failure (ADHF). METHODS: ADHF patients admitted to hospital with pulmonary artery wedge pressure (PAWP)≥18 mm Hg were enrolled. Patients received nicorandil by an intravenous bolus injection of 0.2mg/kg/5 min followed by continuous infusion at a rate of 0.05, 0.10, or 0.20mg/kg/h for 6h. RESULTS: Nicorandil administration caused a significant decrease in PAWP and increase in the cardiac index (CI) that began immediately after the injection and were maintained during the continuous infusion. After 6h, nicorandil administration at 0.2mg/kg/5 min followed by 0.20mg/kg/h resulted in a decrease in PAWP (26.5%, p<0.01), an increase in CI (15.8%, p<0.05), and a decrease in total peripheral resistance (13.8%, p<0.01) in a dose-dependent manner. Nicorandil decreased blood pressure significantly, without an excessive decrease or negative impact even in patients with lower systolic blood pressure. CONCLUSION: Intravenous administration of nicorandil, by bolus injection followed by continuous infusion, improves PAWP and CI in ADHF patients immediately and continuously as a potent vasodilator with combined preload and afterload reduction. These results demonstrate that nicorandil is a safe and effective new medication for the treatment of ADHF.

Synchronous radiation with Er:YAG and Ho:YAG lasers for efficient ablation of hard tissues.

Er:YAG and Ho:YAG laser beams were combined to irradiate hard tissues to achieve highly efficient ablation with low laser power. The delay time between pulses of the two lasers was controlled to irradiate alumina ceramic balls used as hard tissue models. With optimized delay time, the combined laser beam perforated the sample 40% deeper than independent radiation by either an Er:YAG or Ho:YAG laser. An ultra-high-speed camera and an infrared thermography camera were used to observe and investigate the ablation mechanisms.

Impact of implanted bone marrow progenitor cell composition on limb salvage after cell implantation in patients with critical limb ischemia.

OBJECTIVE: The aim of this study is to identify which factors influence limb salvage after bone marrow mononuclear cell implantation (BMI) in patients with chronic critical limb ischemia (CLI). METHODS: Thirteen no-option CLI patients treated with BMI were enrolled in the present study. Limb ischemia was assessed using the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO(2)), and rest pain score. The cell populations among the implanted cells were determined by May-Giemsa staining and flow cytometry. RESULTS: Major lower extremity amputations after BMI were performed in seven patients. Before implantation, there were no significant differences between the amputation group (n=7) and the salvage group (n=6) in clinical characteristics, the ABI, the TcO(2) level, or the rest pain score. After implantation, there were no differences between the groups in the serum levels of angiogenic or inflammatory cytokines. The number of implanted BM cells was the same in the two groups, but the cells implanted in the limb salvage group were composed of significantly higher numbers of hematopoietic progenitors (erythroblasts and myeloblasts) and lymphocytes (p<0.05, respectively). The number of CD34-positive cells was somewhat greater in the salvage group than in the amputation group (p=0.09) and was positively associated with the number of erythroblasts (r(2)=0.29, p=0.06) and the number of myeloblasts (r(2)=0.59, p<0.01). CONCLUSIONS: The cellular composition of the BM cells injected may affect limb salvage after the implantation in patients with severe CLI. The favorable effects of BMI appear to reflect the impact of the progenitor cell doses.

Hollow-fiber-based flexible probe for remote measurement of infrared attenuated total reflection.

A hollow optical-fiber probe for infrared attenuated total reflection (ATR) spectroscopy is developed. A newly designed ATR prism, optimized for use with hollow optical fibers, is proposed. Results from preliminary experiments show the potential uses of the probe in clinical applications. The probe is appropriate for in vivo applications because it is consists of only nontoxic and chemically durable materials.

Eosinophils may be involved in thrombus growth in acute coronary syndrome.

Thrombus aspiration therapy allows for the examination of thrombus and atheroma fragments in acute coronary syndrome (ACS). Inflammatory cells and platelet activation play key roles in thrombus formation in ACS. However, histopathologic evaluation of thrombi in ACS has not been adequately addressed. We performed histologic analysis of tissue samples obtained by thrombus aspiration therapy. We studied 165 samples from patients with ACS. The area of each sample, percentage of red thrombus, and percentage of white thrombus were measured. Samples were stained immunohistochemically with antibodies against macrophages, activated platelets, and interleukin (IL)-5. Seventy-six samples included atheroma fragments. Macrophages, neutrophils, and activated platelets were observed in thrombi and in atheroma fragments. Eosinophil infiltration was also observed predominantly in the area between white thrombus and red thrombus in 106 samples. We categorized all samples into 3 groups according to the grade of eosinophil infiltration (eos-, eos+, eos++ group). Sample area in the eos++ group was greater than that in the eos- group (P < 0.0001). In addition, the percentage of the red thrombus areas in the eos++ group and the eos+ group was greater than that in the eos- group (P < 0.009, P < 0.02, respectively). However, there was no difference in the percentage of white thrombus area between the 3 groups. Staining for IL-5 was identified in inflammatory cells within thrombi. Eosinophils may play an important role in coronary occlusion by promoting thrombus growth.

Surface-plasmon resonance sensor using silica-core Bragg fiber.

A silica-core Bragg fiber surface-plasmon resonance (SPR) sensor with high design flexibility has been developed for refractive index measurement. In this geometry, an HE11-like Bragg fiber core mode is designed to excite the surface plasmonic wave. It is shown that reduction of core size enables measurement of refractive index significantly lower than that of the silica core. This makes the device useful for biosensing or chemical sensing applications handling aqueous samples. The proposed sensor is fabricated using a unique rf-sputtering method, and SPR-induced extinction of more than 20 dB is observed.

Inhibitory effect of valsartan against progression of left ventricular dysfunction after myocardial infarction: T-VENTURE study.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) reduce the mortality in the chronic phase of myocardial infarction (MI), and similar effects of angiotensin receptor blockers (ARB) have been reported. However, these effects of ARB have not yet been established in Japanese patients. A multicenter randomized study was designed for the present study to examine the effect of valsartan as compared to that of ACEI against left ventricular dysfunction after MI. METHODS AND RESULTS: Patients with acute MI were randomly allocated to either the valsartan group (n=120; mean age 63 +/-1.0) or the ACEI group (n=121; mean age 62.9 +/-1.0) and followed up until 6 months. Left ventriculography was performed during hospital admission and at 6 months. The blood pressure was similar in the 2 groups throughout the study. The incidences of cardiovascular events and target vessel revascularization were similar, although that of adverse events was significantly higher in the ACEI (12.4%) than in the valsartan group (3.3%; P<0.05). There were no differences in left ventricular ejection fraction and left ventricular end-diastolic volume index between the groups. CONCLUSIONS: Valsartan exhibits similar efficacy effective to that of ACEI in preventing left ventricular dysfunction in Japanese patients with acute MI, and is, in addition, better tolerated than ACEI.

Improvement and analysis of a micro Raman probe.

A micro Raman probe (MRP) with a 600 microm diameter, which we previously reported as the narrowest achieved to date, was further improved by introducing high-quality optical filters and a collecting lens at the tip. We fabricated the MRP with a high collection efficiency, a wider collection wavelength, and a high signal-to-noise ratio. We compared two types of probes: one with a lens-tipped end and one with a flat tip. We experimentally tested the performance of these MRPs to evaluate the detection properties defined by parameters such as the optical purity against inherent Raman background noise due to optical fibers, the sensitivity, and the viewing area. Finally, we demonstrated their effectiveness in measurements of standard Raman samples and applied them to measurements of plastic and human skin samples in situ.