Oxygen concentration in living organisms is one of the important vital indicators in emergency care and bedside medical settings. However, the oximetry method has limitations: the measurement site is ...limited to the tissue containing blood and the absolute value of oxygen concentration cannot be measured. To overcome these limitations, in this work, we develop a new oxygen sensor that can directly measure the oxygen particle pressure (<inline-formula> <tex-math notation="LaTeX">p\text{O}_{2} </tex-math></inline-formula>) on the surface of the body and organs. A light emitting diode (LED) and a photodiode (PD) were embedded in a dimethylpolysiloxane substrate mixed with carbon nanotubes. The effectiveness of the device was evaluated using calibration, bending strain tests, time and frequency response, and finally in vivo assessments. The results reveal that the calibration experiment of the fabricated oxygen sensor device showed high sensitivity. The carbon nanotube electrode has a sufficient bending resistance and does not affect the response characteristics of the LED and PD, that is, it does not affect the oxygen measurement. In vivo assessment shows that the developed patch-type flexible oxygen sensor can accurately measure <inline-formula> <tex-math notation="LaTeX">p\text{O}_{2} </tex-math></inline-formula> by attaching it to tissues or organs having irregularities or curved surfaces and actual measurements on rat liver surface demonstrated its feasibility.
Abstract Objective Subarachnoid hemorrhage (SAH) causes cerebral ischemia and drastically worsens the clinical status at onset. However, the arterial flow is surprisingly well maintained on the ...cerebral surface. We investigated cortical microcirculatory changes in the super acute phase of SAH using two-photon laser scanning microscopy (TPLSM). Methods SAH was induced at the skull base in 10 mice using a prone endovascular perforation model. Before SAH, and 1, 2, 5, 10, 20, 30 and 60 min
after SAH, the cortical microcirculation was observed with TPLSM through a cranial window. Diameters of penetrating and precapillary arterioles were measured and red blood cell (RBC) velocities in precapillary arterioles were analyzed using a line-scan method after administration of Q-dot 655 nanocrystals. Results One minute after SAH, RBC velocity and flow in precapillary arterioles drastically decreased to
< 20
% of the pre-SAH values, while penetrating and precapillary arterioles dilated significantly. Subsequently, the arterioles either dilated or constricted inconsistently for 60 min
with continual decreases in RBC velocity and flow in the arterioles, suggesting neurovascular dysfunction. Conclusion SAH caused sudden worsening of the cortical arteriolar velocity and flow at onset. The neurovascular unit cannot function sufficiently to maintain cortical microcirculatory flow in the super acute phase of SAH.
Purpose
The purpose of this study was to evaluate the possible clinical application of optical coherence tomography for assessing ovarian reserve in individual specimens of human ovarian tissue for ...fertility preservation.
Methods
Ovarian tissue examination by optical coherence tomography was performed before ovarian tissue cryopreservation. Three of the four subjects had hematological disease or cancer, and they faced a threat to their fertility due to impending chemotherapy. One patient underwent ovarian tissue extraction for in vitro activation of dormant follicles as fertility treatment.
Results
The current full-field optical coherence tomography technique can detect primordial follicles in non-fixed and non-embedded human ovarian tissue. These images are well correlated with histological evaluation and the ovarian reserve test, including follicle counts.
Conclusion
It was demonstrated that optical coherence tomography could assess localization of primordial follicles and ovarian reserve in specimens of non-fixed human ovarian cortex, although optimization for examination of human ovarian tissue is needed for clinical application. Additionally, this technique holds the possibility of assessing the ovarian reserve of patients with unevaluable ovarian reserve.
Trial registration number
UMIN000023141
Background
It is believed that increased intracranial pressure immediately after subarachnoid hemorrhage (SAH) causes extensive brain ischemia and results in worsening clinical status. Arterial flow ...to the cerebral surfaces is clinically well maintained during clipping surgery regardless of the severity of the World Federation of Neurological Societies grade after SAH. To explore what kinds of changes occur in the cortical microcirculation, not at the cerebral surface, we examined cortical microcirculation after SAH using two-photon laser scanning microscopy (TPLSM).
Methods
SAH was induced in mice with an endovascular perforation model. Following continuous injection of rhodamine 6G, velocities of labeled platelets and leukocytes and unlabeled red blood cells (RBCs) were measured in the cortical capillaries 60 min after SAH with a line-scan method using TPLSM, and the data were compared to a sham group and P-selectin monoclonal antibody-treated group.
Results
Velocities of leukocytes, platelets, and RBCs in capillaries decreased significantly 60 min after SAH. Rolling and adherent leukocytes suddenly prevented other blood cells from flowing in the capillaries. Flowing blood cells also decreased significantly in each capillary after SAH. This no-reflow phenomenon induced by plugging leukocytes was often observed in the SAH group but not in the sham group. The decreased velocities of blood cells were reversed by pretreatment with the monoclonal antibody of P-selection, an adhesion molecule expressed on the surfaces of both endothelial cells and platelets.
Conclusions
SAH caused sudden worsening of cortical microcirculation at the onset. Leukocyte plugging in capillaries is one of the reasons why cortical microcirculation is aggravated after SAH.
Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. ...We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is a considerable discrepancy between oxygen supply and demand in the liver because hepatic oxygen consumption is relatively high but about 70% of the hepatic blood supply is poorly oxygenated ...portal vein blood derived from the gastrointestinal tract and spleen. Oxygen is delivered to hepatocytes by blood flowing from a terminal branch of the portal vein to a central venule via sinusoids, and this makes an oxygen gradient in hepatic lobules. The oxygen gradient is an important physical parameter that involves the expression of enzymes upstream and downstream in hepatic microcirculation, but the lack of techniques for measuring oxygen consumption in the hepatic microcirculation has delayed the elucidation of mechanisms relating to oxygen metabolism in liver. We therefore used FITC-labeled erythrocytes to visualize the hepatic microcirculation and used laser-assisted phosphorimetry to measure the partial pressure of oxygen in the microvessels there. Noncontact and continuous optical measurement can quantify blood flow velocities, vessel diameters, and oxygen gradients related to oxygen consumption in the liver. In an acute hepatitis model we made by administering acetaminophen to mice we observed increased oxygen pressure in both portal and central venules but a decreased oxygen gradient in the sinusoids, indicating that hepatocyte necrosis in the pericentral zone could shift the oxygen pressure up and affect enzyme expression in the periportal zone. In conclusion, our optical methods for measuring hepatic hemodynamics and oxygen consumption can reveal mechanisms related to hepatic disease.
New blood vessels that form within tumors undergo repeated irregular divergence, joining, and twisting, resulting in blood vessels with abnormal tissue distribution, structure, and function. Tumor ...vessels exhibit increased spatially uneven permeability and oxygen delivery, characteristics that may reduce the efficacy of radiotherapy and chemotherapy. Therefore, it is vital to establish technologies for quantitatively mapping hypoxia and vessel permeability within tumors to clarify tumor mechanisms. However, existing methods can only acquire mean measurements within a given region or the entire tissue, and there have been no reports of technologies for measuring permeability at multiple points in individual vessels or for simultaneously performing oxygen partial pressure mapping. Here, new blood vessels formed within tumors were detected on fluorescent blood flow images, and measurement points were set at fixed intervals across individual blood vessels. Fluorescent dye that leaked out over time was excited with a continuous wave optical laser to calculate the permeability distribution of individual vessels. On the other hand, an oxygen probe dye was excited with a pulse laser and oxygen concentration-dependent light emission was analyzed to map oxygen partial pressure. Oxygen partial pressure imaging in tumors transplanted onto the backs of mice showed that tissue regions surrounding minute tumor vessels were generally hypoxic. Furthermore, compared with the normal dermal vasculature, there was greater variation in vessel permeability, and sites with very high vessel permeability were detected. We designed a system for high-resolution spatial mapping of blood vessel permeability and tissue oxygenation in tumor microvasculatures, thereby clarifying the relationship between local hypoxia and vessel permeability. It is anticipated that these findings could be applied to improve anticancer drug delivery and radiotherapy by identifying the dependence of local tissue oxygenation on the vessel structure and hemodynamics.
Abstract Gas gradients (e.g., oxygen and nitric oxide) and chemical gradients (e.g., cytokines) are determinants of biological functions and pathological mechanisms, but these have not been ...replicated in vitro. We developed a cell culture microfluidic device that comprises three layers (gas channel, fluid, and cell culture layer) and can generate stable chemical and oxygen gradients simultaneously or independently. The simulated chemical and oxygen gradients were compared with actual measurements based on fluorescence and phosphorescence. The chemical gradients were in good agreement, but the calculated oxygen gradients were estimated to be lower than the measured values. Endothelial cell network formation was inhibited according to the gradient of angiogenesis inhibitors, and tumor cells stained with hypoxia-sensitive dyes fluoresced according to the oxygen gradient. This novel device, which generates chemical and gas gradients, can have many potential applications in physiological and pathological models and in drug screening.
Objective
Hypoxia‐inducible factor is a hypoxia‐responsive transcriptional factor that controls the expression of proteins contributing to homeostatic responses to hypoxia. Spatial heterogeneity of ...tissue oxygenation has been postulated as a determinant of structure and function of hepatic lobules, although its molecular mechanisms remain unknown. This study aimed to examine the role of HIF‐1 expressed in hepatocytes in regulation of hepatic microcirculation.
Methods
We have generated mice harboring a floxed HIF‐1α allele, and employed the albumin‐Cre transgenic line to inactivate the gene site‐specifically in hepatocytes.
Results
Intravital observation of the hepatic microcirculation revealed extension of hepatic lobules in HIF‐1α‐deficient mice. Measurement of microvascular diameter, velocity, and local oxygen tension by laser‐assisted phosphorimetry showed that the oxygen consumption in the lobules of HIF‐1α‐deficient mice was greater than that in those of control mice. Isolated hepatocytes from HIF‐1α‐deficient mice also stimulated oxygen consumptions with increased contents of mtDNA. Overexpression of HIF‐1α decreased the expression of PGC‐1α mRNA, whereas the knockdown of the HIF‐1α gene increased it, suggesting that HIF‐1 regulates cellular respiration through mitochondrial biogenesis.
Conclusions
Our results suggest that constitutive expression of HIF‐1α in hepatocytes acts as a determinant of hepatic lobular structure and oxygen consumption by changing mitochondrial contents.
SUMMARY
Tumor hypoxia is considered a potential therapeutic problem because it reduces the effects of radiation therapy. Clinical experience has shown that long‐term tumor oxygenation cannot be ...achieved with oxygen inhalation, but the mechanisms behind this phenomenon remain unknown. In this study, we designed an optical system for evaluating spatiotemporal changes in tissue oxygen tension (pO2) by phosphorescence quenching. The system can measure continuous changes in pO2 at a fixed point and can also perform two‐dimensional mapping of pO2 in any part of the tumor tissue. We implanted tumor tissue in a dorsal skinfold chamber (DSC) of C57BL/6 mice and observed tumor growth. The mice received oxygen inhalation and pO2 was measured. Tumor pO2 increased after inhalation but the oxygen level was not maintained despite continuous inhalation of pure oxygen; the tumor returned to a hypoxic state. These results mimic the clinical experience of oxygen inhalation treatment in radiation therapy. Our system reproduces the repeat hypoxic phenomenon in a murine tumor model and can be used to determine the mechanisms of oxygen metabolism in tumors.
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