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Magnetic Resonance in Medical Sciences... May 2024We aimed to investigate the changes in intravoxel incoherent motion (IVIM) and diffusion parameters between in vivo and post-mortem conditions and the time dependency of...
PURPOSE
We aimed to investigate the changes in intravoxel incoherent motion (IVIM) and diffusion parameters between in vivo and post-mortem conditions and the time dependency of these parameters using two different mouse tumor models with different vessel lumen sizes.
METHODS
Six B16 and six MDA-MB-231 xenograft mice were scanned using 7 Tesla MRI under both in vivo/post-mortem conditions. Diffusion weighted imaging with 17 b-values (0-3000 s/mm) were obtained at two diffusion times (9 and 27.6 ms). The shifted apparent diffusion coefficient (sADC) using 2 b-values (200 and 1500 s/mm), non-Gaussian diffusion and IVIM parameters (ADC, K, f) were estimated at each of the diffusion times. The results were evaluated by repeated measures two-way analysis of variance and post hoc Bonferroni test.
RESULTS
In B16 tumors, f significantly decreased with post-mortem conditions (from 12.6 ± 6.5% to 5.2 ± 1.9%, P < 0.05 at long diffusion time; from 11.0 ± 2.4% to 4.6 ± 2.7%, P < 0.05 at short diffusion time). In MDA-MB-231 tumors, f also significantly decreased (from 8.8 ± 3.8% to 2.6 ± 1.1%, P < 0.05 at long; from 7.9 ± 5.4% to 2.9 ± 1.1%, P < 0.05 at short). No diffusion time dependency was observed (P = 0.59 in B16 and P = 0.77 in MDA-MB-231). The sADC and ADC values tended to decrease and the K value tended to increase after sacrificing and when increasing the diffusion time.
CONCLUSION
The f values dropped after sacrificing, confirming that IVIM MRI is a promising quantitative parameter to evaluate blood microcirculation. The presence of residual post-mortem f values suggested that the influence of water molecule diffusion in the blood lumen may contribute to the IVIM effect. Diffusion MRI parameter's time dependency and those changes after sacrificing could possibly provide additional insights into diffusion hindrance mechanisms.
PubMed: 38797683
DOI: 10.2463/mrms.mp.2023-0078 -
Laboratory Investigation; a Journal of... May 2024Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the...
Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor β among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.
PubMed: 38797344
DOI: 10.1016/j.labinv.2024.102087 -
The Journal of Investigative Dermatology May 2024
PubMed: 38797323
DOI: 10.1016/j.jid.2024.04.019 -
Journal of Personalized Medicine May 2024Cardiovascular disease (CVD) is the most frequent cause of death worldwide. The alterations in the microcirculation may predict the cardiovascular mortality. The retinal... (Review)
Review
Cardiovascular disease (CVD) is the most frequent cause of death worldwide. The alterations in the microcirculation may predict the cardiovascular mortality. The retinal vasculature can be used as a model to study vascular alterations associated with cardiovascular disease. In order to quantify microvascular changes in a non-invasive way, fundus images can be taken and analysed. The central retinal arteriolar (CRAE), the venular (CRVE) diameter and the arteriolar-to-venular diameter ratio (AVR) can be used as biomarkers to predict the cardiovascular mortality. A narrower CRAE, wider CRVE and a lower AVR have been associated with increased cardiovascular events. Dynamic retinal vessel analysis (DRVA) allows the quantification of retinal changes using digital image sequences in response to visual stimulation with flicker light. This article is not just a review of the current literature, it also aims to discuss the methodological benefits and to identify research gaps. It highlights the potential use of microvascular biomarkers for screening and treatment monitoring of cardiovascular disease. Artificial intelligence (AI), such as Quantitative Analysis of Retinal vessel Topology and size (QUARTZ), and SIVA-deep learning system (SIVA-DLS), seems efficient in extracting information from fundus photographs and has the advantage of increasing diagnosis accuracy and improving patient care by complementing the role of physicians. Retinal vascular imaging using AI may help identify the cardiovascular risk, and is an important tool in primary cardiovascular disease prevention. Further research should explore the potential clinical application of retinal microvascular biomarkers, in order to assess systemic vascular health status, and to predict cardiovascular events.
PubMed: 38793083
DOI: 10.3390/jpm14050501 -
Medicina (Kaunas, Lithuania) Apr 2024The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of... (Review)
Review
The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.
Topics: Humans; Cardiac Output; Cardiotonic Agents; Dobutamine; Hemodynamics; Shock, Septic; Animals
PubMed: 38792934
DOI: 10.3390/medicina60050751 -
Journal of Clinical Medicine May 2024This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence...
This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence tomography angiography (OCT-A). Twenty-four eyes of 24 patients with inactive SLE under hydroxychloroquine (HCQ) therapy were included. The OCT-A data (mainly vessel density (VD) and foveal avascular zone (FAZ) data of the superficial and of the deep capillary plexus (SCP, DCP) and the choriocapillaris (CC)) were analyzed and compared between the baseline examination (t) and 2 years later (t). At t, VD in the whole en face SCP and in the CC was notably reduced compared to t (SCP: = 0.001, CC: = 0.013). VD in the DCP, CRT and FAZ area showed no difference at t compared to t (DCP: = 0.128, FAZ: = 0.332, CRT fovea: = 0.296). Correlation analysis between the increase in cumulative doses of HCQ between t and t and the VD of the whole en face SCP did not show any correlation (Spearman r = 0.062 (95% CI -0.367; 0.477). SLE patients demonstrated a decrease in the retinal VD of the SCP and CC over a 2-year period. There was no correlation with the change in cumulative doses of HCQ. These results suggest an ongoing effect of the disease on the retinal and choriocapillary microcirculation.
PubMed: 38792521
DOI: 10.3390/jcm13102979 -
Journal of Clinical Medicine May 2024: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and...
: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([Tc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. : Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics ( < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels ( < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.
PubMed: 38792441
DOI: 10.3390/jcm13102900 -
Journal of Clinical Medicine May 2024The aim of this study was to investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise...
UNLABELLED
The aim of this study was to investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators.
DESIGN
This study was a single- center pilot trial.
SETTING
The study took place in the Faculty of Health, Tsukuba University of Technology, Japan.
PARTICIPANTS
Hypertensive community-dwelling elderly people took part in the study.
INTERVENTION
Microcirculation was observed before and 1 min after an arm-curl exercise by means of capillary microscopy of the non-exercised limb. Additionally, we examined other health-related indicators. : We measured the acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters. There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3 ± 6.7 to 2.7 ± 0.2 log µm/s ( < 0.01), and the capillary density changed from 0.8 ± 0.2 to 0.9 ± 0.1 log/mm ( < 0.01), which included a significant increase in the non-exercising limb. Significant correlations were observed between the nailfold capillary diameter and body fat mass, the capillary diameter and physical activity, and the capillary density and bone mineral density. The acute effects of exercise on high-risk elderly individuals can be safe, and even 1 of min exercise can potentially improve their nailfold capillary function, despite the brief time, compared to no exercise. The results indicate that capillaries have an impact on the function of the whole body. Thus, they may be a useful diagnostic tool for assessing nailfold capillaries.
PubMed: 38792358
DOI: 10.3390/jcm13102818 -
International Journal of Molecular... May 2024Sigma non-opioid intracellular receptor 1 (Sigma-1R) is an intracellular chaperone protein residing on the endoplasmic reticulum at the mitochondrial-associated membrane...
Sigma non-opioid intracellular receptor 1 (Sigma-1R) is an intracellular chaperone protein residing on the endoplasmic reticulum at the mitochondrial-associated membrane (MAM) region. Sigma-1R is abundant in the brain and is involved in several physiological processes as well as in various disease states. The role of Sigma-1R at the blood-brain barrier (BBB) is incompletely characterized. In this study, the effect of Sigma-1R activation was investigated in vitro on rat brain microvascular endothelial cells (RBMVEC), an important component of the blood-brain barrier (BBB), and in vivo on BBB permeability in rats. The Sigma-1R agonist PRE-084 produced a dose-dependent increase in mitochondrial calcium, and mitochondrial and cytosolic reactive oxygen species (ROS) in RBMVEC. PRE-084 decreased the electrical resistance of the RBMVEC monolayer, measured with the electric cell-substrate impedance sensing (ECIS) method, indicating barrier disruption. These effects were reduced by pretreatment with Sigma-1R antagonists, BD 1047 and NE 100. In vivo assessment of BBB permeability in rats indicates that PRE-084 produced a dose-dependent increase in brain extravasation of Evans Blue and sodium fluorescein brain; the effect was reduced by the Sigma-1R antagonists. Immunocytochemistry studies indicate that PRE-084 produced a disruption of tight and adherens junctions and actin cytoskeleton. The brain microcirculation was directly visualized in vivo in the prefrontal cortex of awake rats with a miniature integrated fluorescence microscope (aka, miniscope; Doric Lenses Inc.). Miniscope studies indicate that PRE-084 increased sodium fluorescein extravasation in vivo. Taken together, these results indicate that Sigma-1R activation promoted oxidative stress and increased BBB permeability.
Topics: Animals; Receptors, sigma; Blood-Brain Barrier; Sigma-1 Receptor; Rats; Reactive Oxygen Species; Endothelial Cells; Male; Mitochondria; Calcium; Morpholines; Brain; Cells, Cultured
PubMed: 38791182
DOI: 10.3390/ijms25105147 -
Biomedicines May 2024This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen...
This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests.
PubMed: 38790982
DOI: 10.3390/biomedicines12051020