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Ophthalmic Research 2022Central serous chorioretinopathy (CSCR) is a chorioretinal disorder resulting from choroidal hyperpermeability. Its comorbidities as hypertension, coronary disease, and... (Observational Study)
Observational Study
BACKGROUND
Central serous chorioretinopathy (CSCR) is a chorioretinal disorder resulting from choroidal hyperpermeability. Its comorbidities as hypertension, coronary disease, and psychological stress, suggest that it might reflect a more generalized vascular dysfunction.
OBJECTIVES
The aim of the study was to assess the cerebrovascular regulation integrity, using cerebral autoregulation (CA), carbon dioxide vasoreactivity (VR), and neurovascular coupling (NVC) in CSCR.
METHODS
This observational pilot study included 20 CSCR patients and 14 age- and sex-matched controls. A State-Trait Anxiety Inventory (STAI) inquiry was full-filled. Continuous measurement of cerebral blood flow velocity (CBFV), arterial blood pressure, heart rate, and end-tidal carbon dioxide was performed. VR was assessed during hypercapnia (inhaling carbogen gas) and hypnocapnia (hyperventilation). For NVC, the CBFV relative increase during mental activation using the N-Back Task was calculated.
RESULTS
No significant differences in systemic hemodynamic parameters, CA or VR, were found between both groups. During the NVC performance, the average CBFV rise during mental stress was significantly lower in CSCR (p = 0.011). A significant negative correlation was found between STAI scores and NVC.
CONCLUSIONS
CSCR patients presented a significantly impaired cerebral NVC compared to controls, supporting the theory of a potential systemic vascular dysfunction. Stress could be related to this NVC impairment.
Topics: Carbon Dioxide; Central Serous Chorioretinopathy; Homeostasis; Humans; Neurovascular Coupling
PubMed: 32564029
DOI: 10.1159/000509553 -
OncoTargets and Therapy 2016The aim of this study was to investigate whether the blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) can evaluate tumor maturity and...
Blood oxygenation level-dependent magnetic resonance imaging during carbogen breathing: differentiation between prostate cancer and benign prostate hyperplasia and correlation with vessel maturity.
OBJECTIVE
The aim of this study was to investigate whether the blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) can evaluate tumor maturity and preoperatively differentiate prostate cancer (PCa) from benign prostate hyperplasia (BPH).
PATIENTS AND METHODS
BOLD MRI based on transverse relaxation time*-weighted echo planar imaging was performed to assess PCa (19) and BPH (22) responses to carbogen (95% O2 and 5% CO2). The average signal values of PCa and BPH before and after carbogen breathing and the relative increased signal values were computed, respectively. The endothelial-cell marker, CD31, and the pericyte marker, α-smooth muscle actin (mature vessels), were detected with immunofluorescence, and were assessed by microvessel density (MVD) and microvessel pericyte density (MPD). The microvessel pericyte coverage index (MPI) was used to evaluate the degree of vascular maturity. The changed signal from BOLD MRI was correlated with MVD, MPD, and MPI.
RESULTS
After inhaling carbogen, both PCa and BPH showed an increased signal, but a lower slope was found in PCa than that in BPH (P<0.05). PCa had a higher MPD and MVD but a lower MPI than BPH. The increased signal intensity was positively correlated with MPI in PCa and that in BPH (r=0.616, P=0.011; r=0.658, P=0.002); however, there was no correlation between the increased signal intensity and MPD or MVD in PCa than that in BPH (P>0.05).
CONCLUSION
Our results confirmed that the increased signal values induced by BOLD MRI well differentiated PCa from BPH and had a positive correlation with vessel maturity in both of them. BOLD MRI can be utilized as a surrogate marker for the noninvasive assessment of the degree of vessel maturity.
PubMed: 27462169
DOI: 10.2147/OTT.S105480 -
Magnetic Resonance in Medicine Jan 2009Magnetic resonance imaging has shown promise for evaluating tissue oxygenation. In this study differences in the tissue longitudinal relaxation rate (R(1)) and effective... (Comparative Study)
Comparative Study
Magnetic resonance imaging has shown promise for evaluating tissue oxygenation. In this study differences in the tissue longitudinal relaxation rate (R(1)) and effective transverse relaxation rate (R(*)(2)), induced by inhalation of pure oxygen and carbogen, were evaluated in 10 healthy subjects. Significant reductions in R(1) were demonstrated following both oxygen and carbogen inhalation in the spleen (both P < 0.001), liver (P = 0.002 air vs. oxygen; P = 0.001 air vs. carbogen), skeletal muscle (both P < 0.001), and renal cortex (P = 0.005 air vs. oxygen; P = 0.008 air vs. carbogen). No significant change in R(*)(2) occurred following pure oxygen in any organ. However, a significant increase in R(*)(2) was observed in the spleen (P < 0.001), liver (P = 0.001), skeletal muscle (P = 0.026), and renal cortex (P = 0.001) following carbogen inhalation, an opposite effect to that observed in many studies of tumor pathophysiology. Changes in R(1) and R(*)(2) were independent of the gas administration order in the spleen and skeletal muscle. These findings suggest that the R(1) and R(*)(2) responses to hyperoxic gases are independent biomarkers of oxygen physiology.
Topics: Administration, Inhalation; Adult; Algorithms; Carbon Dioxide; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Metabolic Clearance Rate; Organ Specificity; Oxygen; Pattern Recognition, Automated; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution
PubMed: 19097212
DOI: 10.1002/mrm.21815 -
The British Journal of Cancer.... Jul 1996The 40-year history of hypoxic cell sensitisation can be traced from hyperbaric oxygen to the present clinical studies with carbogen, nicotinamide and accelerated... (Review)
Review
The 40-year history of hypoxic cell sensitisation can be traced from hyperbaric oxygen to the present clinical studies with carbogen, nicotinamide and accelerated radiotherapy. A meta-analysis by Overgaard (1995) included 10703 cases entered into 83 randomised controlled trials and showed an overall improvement in local tumour control of 4.6% (P = 0.00001) and in survival of 2.8% (P = 0.005). Hyperbaric oxygen gave a 6.6% (P = 0.003) improvement in local control and hypoxic cell sensitisers 3.9% (P = 0.04). Despite this, the only hypoxic cell-sensitising method in routine clinical use is the giving of nimorazole in supraglottic and pharyngeal carcinomas. Acute, as well as chronic hypoxia has been recognised and nicotinamide, the amide derivative of B3 is believed to prevent the former. Thus ARCON (accelerated radiotherapy, carbogen and nicotinamide) has been introduced in the clinic in an effort to overcome tumour proliferation, chronic and acute hypoxia, respectively. The success of future randomised controlled trials would be improved greatly if methods were available to measure the concentration of hypoxic cells in tumours before treatment and thus select those where benefit may be gained. The use of ARCON recognises that tumour cell proliferation is an important cause of failure in addition to hypoxia. However, intrinsic radiosensitivity may also need to be taken into account in the future. Clinical trials aim to improve the therapeutic ratio and thus the study of morbidity is as important as local tumour control. International collaboration is essential if randomised controlled trials are to be carried out within reasonable periods of time.
Topics: Blood Transfusion; Carbon Dioxide; Cell Hypoxia; Humans; Hyperbaric Oxygenation; Neoplasms; Niacinamide; Oxygen; Radiation-Sensitizing Agents
PubMed: 8763896
DOI: No ID Found -
Journal of Audiology & Otology Apr 2017Viral and vascular disorders are considered to be a major cause of idiopathic sudden sensorineural hearing loss (ISSNHL). Lipoprostaglandin E (lipo-PGE) has vasodilating...
BACKGROUND AND OBJECTIVES
Viral and vascular disorders are considered to be a major cause of idiopathic sudden sensorineural hearing loss (ISSNHL). Lipoprostaglandin E (lipo-PGE) has vasodilating activity and has been used to treat ISSNHL. The purpose of this study was to determine the specific therapeutic effects of lipo-PGE and compare them to other treatment modalities for ISSNHL.
SUBJECTS AND METHODS
The study group had 1,052 patients diagnosed with ISSNHL. All were treated with steroid, carbogen inhalation, stellate ganglion block (SGB), or PGE. The CP group (steroid, carbogen inhalation, and PGE1 injection; 288 patients) was treated with lipo-PGE and carbogen inhalation, the CS group (steroid, carbogen inhalation, and stellate ganglion block; 232 patients) with steroid, carbogen inhalation, and SGB, the C group (steroid and carbogen inhalation; 284 patients) with steroid and carbogen, and the control group (steroid only; 248 patients) with steroid only. Patients in the groups receiving lipo-PGE received a continuous infusion of 10 µL lipo-PGE.
RESULTS
The overall recovery rate after treatment was 52.2%, and recovery rates by group were 67.7% in the CP group, 54.3% in the CS group, 52.1% in the C group, and 32.2% in the control group. Therefore, the therapeutic results in groups treated with lipo-PGE were better than results in other groups. The difference was statistically significant.
CONCLUSIONS
The study results suggested that the CP group received effective treatment modalities for ISSNHL. The combined therapy of lipo-PGE with carbogen inhalation in patients with ISSNHL was more beneficial than other treatment modalities.
PubMed: 28417106
DOI: 10.7874/jao.2017.21.1.33 -
International Journal of Radiation... Mar 2009Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO(2)) limits the ability...
PURPOSE
Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO(2)) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO(2) in rats using a new and potentially widely useful method, multisite in vivo electron paramagnetic resonance oximetry.
METHODS AND MATERIALS
Intracerebral 9L and C6 tumors were established in the left hemisphere of syngeneic rats, and electron paramagnetic resonance oximetry was successfully used for repeated tissue pO(2) measurements after 9.3 Gy of radiation and during carbogen breathing for 5 consecutive days.
RESULTS
Intracerebral 9L gliomas had a pO(2) of 30-32 mm Hg and C6 gliomas were relatively hypoxic, with a pO(2) of 12-14 mm Hg (p < 0.05). The tissue pO(2) of the contralateral brain was 40-45 mm Hg in rats with either 9L or C6 gliomas. Irradiation resulted in a significant increase in pO(2) of the 9L gliomas only. A significant increase in the pO(2) of the 9L and C6 gliomas was observed in rats breathing carbogen, but this effect decreased during 5 days of repeated experiments in the 9L gliomas.
CONCLUSION
These results highlight the tumor-specific effect of radiation (9.3.Gy) on tissue pO(2) and the different responses to carbogen inhalation. The ability of electron paramagnetic resonance oximetry to provide direct repeated measurements of tissue pO(2) could have a vital role in understanding the dynamics of hypoxia during therapy that could then be optimized by scheduling doses at times of improved tumor oxygenation.
Topics: Animals; Brain Neoplasms; Carbon Dioxide; Cell Hypoxia; Chi-Square Distribution; Electron Spin Resonance Spectroscopy; Glioma; Oximetry; Oxygen; Oxygen Consumption; Partial Pressure; Radiation-Sensitizing Agents; Radiotherapy Dosage; Rats; Rats, Inbred F344; Rats, Wistar; Tumor Burden
PubMed: 19136221
DOI: 10.1016/j.ijrobp.2008.10.025 -
Cancer Jun 2005Accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in... (Clinical Trial)
Clinical Trial
BACKGROUND
Accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON.
METHODS
Acute and late morbidity was assessed in 105 patients with high-grade superficial or muscle-invasive bladder carcinoma who were given accelerated radiotherapy (50-55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease-free survival, and locoregional control.
RESULTS
Nearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20-30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies > or = 3 times per day. By 10-12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency < or = 2 times per hour was approximately 75% in both arms. Incidence of severe hematuria (< or = 25%) and urinary urgency (< or = 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone.
CONCLUSIONS
Historical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings.
Topics: Adult; Aged; Aged, 80 and over; Carbon Dioxide; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Hypoxia; Combined Modality Therapy; Disease-Free Survival; Humans; Middle Aged; Niacinamide; Oxygen; Radiotherapy, High-Energy; Survival Rate; Urinary Bladder Neoplasms
PubMed: 15834926
DOI: 10.1002/cncr.21048 -
Oncology Letters Oct 2015The present study aimed to evaluate the feasibility of performing carbogen gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI)...
The present study aimed to evaluate the feasibility of performing carbogen gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) measurements in patients with hepatocellular carcinoma (HCC). A total of 25 patients with HCC underwent T2* mapping derived from multi-echo gradient-recalled echo imaging prior to and following breathing carbogen (95% O and 5% CO) for 10 min. Follow-up T2* mapping was performed in 5 patients 1 day after transarterial chemoembolization (TACE). T2*, R2* and ∆R2* values (R2*air - R2*carb) of the whole tumor, the solid region of the tumor and the adjacent liver parenchyma were measured and compared in the patients with HCC. The T2* value of the solid region of the tumor following carbogen breathing was higher than the value following room air breathing (P<0.05), and the R2* value of room air breathing was higher than that following carbogen breathing (P<0.05). ∆R2* values of the tumor and the adjacent liver parenchyma prior to and following carbogen breathing were 2.4±7.8, 8.1±14.7 and 2.0±11.0 sec, respectively. R2* values were significantly decreased in 2 cases 1 day after TACE (17.8 vs. -3.4 sec and 10.2 vs. 2.4 sec). Overall, carbogen gas-challenge BOLD MRI measurements are feasible in clinical settings and may serve as a novel functional biomarker for monitoring the treatment efficacy of embolic therapies for HCC.
PubMed: 26622788
DOI: 10.3892/ol.2015.3526 -
Scientific Reports Feb 2020Abnormal tumor hemodynamics are a critical determinant of a tumor's microenvironment (TME), and profoundly affect drug delivery, therapeutic efficacy and the emergence...
Abnormal tumor hemodynamics are a critical determinant of a tumor's microenvironment (TME), and profoundly affect drug delivery, therapeutic efficacy and the emergence of drug and radio-resistance. Since multiple hemodynamic variables can simultaneously exhibit transient and spatiotemporally heterogeneous behavior, there is an exigent need for analysis tools that employ multiple variables to characterize the anomalous hemodynamics within the TME. To address this, we developed a new toolkit called HemoSYS for quantifying the hemodynamic landscape within angiogenic microenvironments. It employs multivariable time-series data such as in vivo tumor blood flow (BF), blood volume (BV) and intravascular oxygen saturation (Hb) acquired concurrently using a wide-field multicontrast optical imaging system. The HemoSYS toolkit consists of propagation, clustering, coupling, perturbation and Fourier analysis modules. We demonstrate the utility of each module for characterizing the in vivo hemodynamic landscape of an orthotropic breast cancer model. With HemoSYS, we successfully described: (i) the propagation dynamics of acute hypoxia; (ii) the initiation and dissolution of distinct hemodynamic niches; (iii) tumor blood flow regulation via local vasomotion; (iv) the hemodynamic response to a systemic perturbation with carbogen gas; and (v) frequency domain analysis of hemodynamic heterogeneity in the TME. HemoSYS (freely downloadable via the internet) enables vascular phenotyping from multicontrast in vivo optical imaging data. Its modular design also enables characterization of non-tumor hemodynamics (e.g. brain), other preclinical disease models (e.g. stroke), vascular-targeted therapeutics, and hemodynamic data from other imaging modalities (e.g. MRI).
Topics: Animals; Cell Line, Tumor; Diagnostic Imaging; Female; Hemodynamics; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neovascularization, Pathologic; Software; Systems Biology; Tumor Microenvironment
PubMed: 32047171
DOI: 10.1038/s41598-020-58918-3 -
Scientific Reports Nov 2023Acute brain slices are a common and useful preparation in experimental neuroscience. A wide range of incubation chambers for brain slices exists but only a few are...
Acute brain slices are a common and useful preparation in experimental neuroscience. A wide range of incubation chambers for brain slices exists but only a few are designed with very low volumes of the bath solution in mind. Such chambers are necessary when high-cost chemicals are to be added to the solution or when small amounts of substances released by the slice are to be collected for analysis. The principal challenge in designing a very low-volume incubation chamber is maintaining good oxygenation and flow without mechanically disturbing or damaging the slices. We designed and validated BubbleDrive, a 3D-printed incubation chamber with a minimum volume of 1.5 mL which can hold up to three coronal mouse slices from one hemisphere. It employs the carbogen gas bubbles to drive the flow circulation in a consistent and reproducible manner, and without disturbing the brain slices. The BubbleDrive design and construction were successfully validated by comparison to a conventional large-volume incubation chamber in several experimental designs involving measurements of extracellular diffusion parameters, the electrophysiology of neuronal and astrocytic networks, and the effectiveness of slice incubation with hyaluronidase enzyme.
Topics: Mice; Animals; Brain; Neurons; Astrocytes
PubMed: 37973847
DOI: 10.1038/s41598-023-45949-9