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1.
BMJ Case Rep ; 14(10)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620633

RESUMO

Necrotising myopathy with pipestem capillaries is a distinct form of inflammatory myopathy exhibiting only sparse inflammation on biopsy, with clinical presentation and histopathological profile entirely different from dermatomyositis, polymyositis or inclusion body myositis. A 51-year-old non-diabetic man presents with progressively worsening shortness of breath and myalgias with only mild proximal muscle weakness and elevated serum creatine kinase. Autoimmune workup, ordered after ruling out infectious and cardiac aetiologies, returned positive for Sjögren's syndrome antibody (SSA/Ro-52). Lung imaging and biopsy were suggestive of cryptogenic organising pneumonia and muscle biopsy showed myositis with pipestem capillaries and abnormal deposition of membrane attack complex with only sparse inflammation. The patient received high-dose steroids, mycophenolate mofetil, intravenous immunoglobulin and rituximab with improvement in muscle symptoms. However, his pulmonary findings progressed, requiring evaluation for a lung transplant. This case emphasises the need for further research to better understand this disease entity and improve mortality and morbidity in these patients.


Assuntos
Doenças Pulmonares Intersticiais , Miosite de Corpos de Inclusão , Miosite , Síndrome de Sjogren , Capilares , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/tratamento farmacológico , Miosite/etiologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico
2.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34638535

RESUMO

Lung endothelial cell dysfunction plays a central role in septic-induced lung injury. We hypothesized that endothelial cell subsets, capillary endothelial cells (capEC) and post capillary venules (PCV), might play different roles in regulating important pathophysiology in sepsis. In order to reveal global transcriptomic changes in endothelial cell subsets during sepsis, we induced sepsis in C57BL/6 mice by cecal ligation and puncture (CLP). We confirmed that CLP induced systemic and lung inflammation in our model. Endothelial cells (ECs) from lung capillary and PCV were isolated by cell sorting and transcriptomic changes were analyzed by bioinformatic tools. Our analysis revealed that lung capEC are transcriptionally different than PCV. Comparison of top differentially expressed genes (DEGs) of capEC and PCV revealed that capEC responses are different than PCV during sepsis. It was found that capEC are more enriched with genes related to regulation of coagulation, vascular permeability, wound healing and lipid metabolic processes after sepsis. In contrast, PCV are more enriched with genes related to chemotaxis, cell-cell adhesion by integrins, chemokine biosynthesis, regulation of actin filament process and neutrophil homeostasis after sepsis. In addition, we predicted some transcription factor targets that regulate a significant number of DEGs in sepsis. We proposed that targeting certain DEGs or transcriptional factors would be useful in protecting against sepsis-induced lung damage.


Assuntos
Capilares/metabolismo , Células Endoteliais/metabolismo , Pulmão/patologia , Sepse/patologia , Vênulas/metabolismo , Animais , Ceco/lesões , Modelos Animais de Doenças , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/mortalidade , Sepse/terapia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
3.
Anal Chim Acta ; 1185: 339002, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34711332

RESUMO

As the SARS-CoV-2 pandemic continues to spread, the necessity for rapid, easy diagnostic capabilities could never have been more crucial. With this aim in mind, we have developed a cost-effective and time-saving testing methodology/strategy that implements a sensitive reverse transcriptase loop-mediated amplification (RT-LAMP) assay within narrow, commercially available and cheap, glass capillaries for detection of the SARS-CoV-2 viral RNA. The methodology is compatible with widely used laboratory-based molecular testing protocols and currently available infrastructure. It employs a simple rapid extraction protocol that lyses the virus, releasing sufficient genetic material for amplification. This extracted viral RNA is then amplified using a SARS-CoV-2 RT-LAMP kit, at a constant temperature and the resulting amplified product produces a colour change which can be visually interpreted. This testing protocol, in conjunction with the RT-LAMP assay, has a sensitivity of ∼100 viral copies per reaction of a sample and provides results in a little over 30 min. As the assay is carried out in a water bath, commonly available within most testing laboratories, it eliminates the need for specialised instruments and associated skills. In addition, our testing pathway requires a significantly reduced quantity of reagents per test while providing comparable sensitivity and specificity to the RT-LAMP kit used in this study. While the conventional technique requires 25 µl of reagent, our test only utilises less than half the quantity (10 µl). Thus, with its minimalistic approach, this capillary-based assay could be a promising alternative to the conventional testing, owing to the fact that it can be performed in resource-limited settings, using readily available apparatus, and has the potential of increasing the overall testing capacity, while also reducing the burden on supply chains for mass testing.


Assuntos
COVID-19 , Teste para COVID-19 , Capilares , Técnicas de Laboratório Clínico , Análise Custo-Benefício , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , RNA Viral/genética , DNA Polimerase Dirigida por RNA , SARS-CoV-2 , Sensibilidade e Especificidade
4.
Invest Ophthalmol Vis Sci ; 62(13): 1, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605880

RESUMO

Purpose: The purpose of this study was to assess density and morphology of cone photoreceptors (PRs) and corresponding retinal sensitivity in ischemic compared to nonischemic retinal capillary areas of diabetic eyes using adaptive optics optical coherence tomography (AO-OCT) and microperimetry (MP). Methods: In this cross-sectional, observational study five eyes of four patients (2 eyes with proliferative diabetic retinopathy (DR) and 3 eyes moderate nonproliferative DR) were included. PR morphology and density was manually assessed in AO-OCT en face images both at the axial position of the inner-segment outer segment (IS/OS) and cone outer segment tips (COSTs). Retinal sensitivity was determined by fundus-controlled microperimetry in corresponding areas (MP-3, Nidek). Results: In AO-OCT, areas affected by capillary nonperfusion showed severe alterations of cone PR morphology at IS/OS and COST compared to areas with intact capillary perfusion (84% and 87% vs. 9% and 8% of area affected for IS/OS and COST, respectively). Mean reduction of PR signal density in affected areas compared to those with intact superficial capillary plexus (SCP) and deep capillary plexus (DCP) perfusion of similar eccentricity was -38% at the level of IS/OS (P = 0.01) and -39% at the level of COST (P = 0.01). Mean retinal sensitivity was 10.8 ± 5.4 in areas affected by DCP nonperfusion and 28.2 ± 1.5 outside these areas (P < 0.001). Conclusions: Cone PR morphology and signal density are severely altered in areas of capillary nonperfusion. These structural changes are accompanied by a severe reduction of retinal sensitivity, indicating the importance of preventing impaired capillary circulation in patients with DR.


Assuntos
Retinopatia Diabética/diagnóstico , Isquemia/diagnóstico , Células Fotorreceptoras Retinianas Cones/patologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Testes de Campo Visual/métodos , Adulto , Capilares/patologia , Estudos Transversais , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
Biomater Sci ; 9(19): 6574-6583, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582534

RESUMO

Porphyromonas gingivalis, the pathogen of periodontal disease, is thought to be involved in various diseases throughout the body via gingival tissue blood capillaries. However, the dynamic analysis of the infection mechanism, particularly the deep invasion process of the gingival tissue, has not yet been elucidated because of the lack of both in vivo and in vitro models. In this study, we developed a vascularized three-dimensional (3D) gingival model with an epithelial barrier expressing cell-cell junctions using collagen microfibers (CMFs) to enable the dynamic analysis of the P. gingivalis invasion process. Lipid raft disruption experiments in the gingival epithelial cell layer demonstrated that P. gingivalis migrates into the deeper epithelium via the intercellular pathway rather than intracellular routes. P. gingivalis was shown to invade the 3D gingival model, being found inside blood capillaries during two days of culture. Notably, the number of bacteria had increased greatly at least two days later, whereas the mutant P. gingivalis lacking the cysteine proteases, gingipains, showed a significantly lower number of survivors. The secretion of interleukin-6 (IL-6) from the gingival tissue decreased during the two days of infection with the wild type P. gingivalis, but the opposite was found for the mutant suggesting that P. gingivalis infection disturbs IL-6 secretion at an early stage. By allowing the dynamic observation of the P. gingivalis invasion from the epithelial cell layer into the blood capillaries for the first time, this model will be a powerful tool for the development of novel therapeutics against periodontal infection related diseases.


Assuntos
Capilares , Porphyromonas gingivalis , Células Cultivadas , Células Epiteliais , Gengiva , Humanos
6.
ACS Biomater Sci Eng ; 7(10): 4971-4981, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34503336

RESUMO

Simulating the structure and function of blood capillaries is very important for an in-depth insight into their role in the human body and treatment of capillary-related diseases. Due to the similar composition and structure, hollow hydrogel microfibers are well-recognized as potential biomimetic blood capillaries. In this paper, we report a novel, facile, and reproducible method to fabricate coaxial microfluidic chips via 3D printing-assisted soft lithography and then hollow hydrogel microfibers using the as-prepared coaxial microfluidic chips. Instead of traditional photoresist-based lithography, 3D printing of gelatin hydrogel under various extrusion pressures is used to construct sacrificial templates of coaxial microfluidic chips. Various solid and hollow hydrogel microfibers with complicated and hierarchical structures can be obtained via multitype coaxial microfluidic chips or a combination of coaxial microfluidic fabrication and post-treatment. The as-formed hollow hydrogel microfibers are evaluated in detail as biomimetic blood capillaries, including physicochemical and cytological properties. Our results prove that the hollow hydrogel microfibers exhibit excellent mass transport capacity, hemocompatibility, semipermeability, and mechanical strength, and their barrier function can be further enhanced in the presence of endothelial cells. Overall, our 3D printing-assisted fabrication strategy provides a new technique to construct microfluidic chips with complicated 3D microchannels, and the resulting hollow hydrogel microfibers are promising candidates for blood capillaries.


Assuntos
Hidrogéis , Microfluídica , Biomimética , Capilares , Células Endoteliais , Humanos , Impressão Tridimensional , Engenharia Tecidual
7.
Biophys J ; 120(21): 4859-4873, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34536388

RESUMO

Hepatic sinusoids present complex anatomical structures such as the endothelial sieve pores and the Disse space, which govern the microscopic blood flow in the sinusoids and are associated with structural variations in liver fibrosis and cirrhosis. However, the contributions of the permeability of endothelial and collagen layers and the roughness of hepatocyte microvilli to the features of this microflow remain largely unknown. Here, an immersed boundary method coupled with a lattice Boltzmann method was adopted in an in vitro hepatic sinusoidal model, and flow field and erythrocyte deformation analyses were conducted by introducing three new source terms including permeability of the endothelial layer, resistance of hepatocyte microvilli and collagen layers, and deformation of red blood cells (RBCs). Numerical calculations indicated that alterations in endothelial permeability could significantly affect the flow velocity and flow rate distributions in hepatic sinusoids. Interestingly, a biphasic regulating pattern of shear stress occurred simultaneously on the surface of hepatocytes and the lower side of endothelium, i.e., the shear stress increased with increased thickness of hepatocyte microvilli and collagen layer when the endothelial permeability was high but decreased with the increase of the thickness at low endothelial permeability. Additionally, this specified microflow manipulates typical RBC deformation inside the sinusoid, yielding one-third of the variation of deformable index with varied endothelial permeability. These simulations not only are consistent with experimental measurements using in vitro liver sinusoidal chip but also elaborate the contributions of endothelial and collagen layer permeability and wall roughness. Thus, our results provide a basis for further characterizing this microflow and understanding its effects on cellular migration and deformation in the hepatic sinusoids.


Assuntos
Capilares , Fígado , Eritrócitos , Hemodinâmica , Hepatócitos
8.
PLoS Biol ; 19(9): e3001358, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34520451

RESUMO

Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation. Moreover, the HSHA mice showed impaired performance in the passive avoidance test, suggesting impairment in hippocampal-dependent learning. Transmission electron microscopy shows marked neurovascular disruption in HSHA mice. This study provides causal evidence of a lipoprotein-Aß /capillary axis for onset and progression of a neurodegenerative process.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides/biossíntese , Hepatócitos/metabolismo , Peptídeos beta-Amiloides/genética , Animais , Barreira Hematoencefálica/patologia , Encéfalo/irrigação sanguínea , Capilares/patologia , Modelos Animais de Doenças , Humanos , Inflamação , Aprendizagem , Lipoproteínas/metabolismo , Masculino , Camundongos Transgênicos , Degeneração Neural
9.
Am J Physiol Renal Physiol ; 321(5): F600-F616, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34541901

RESUMO

Following our previous reports on mesangial sclerosis and vascular proliferation in diabetic nephropathy (DN) (Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ. Am J Physiol Renal Physiol 312: F1101-F1111, 2017; Löwen J, Gröne E, Gröne HJ, Kriz W. Am J Physiol Renal Physiol 317: F399-F410, 2019), we now describe the advanced stages of DN terminating in glomerular obsolescence and tubulointerstitial fibrosis based on a total of 918 biopsies. The structural aberrations emerged from two defects: 1) increased synthesis of glomerular basement membrane (GBM) components by podocytes and endothelial cells leading to an accumulation of GBM material in the mesangium and 2) a defect of glomerular vessels consisting of increased leakiness and an increased propensity to proliferate. Both defects may lead to glomerular degeneration. The progressing compaction of accumulated worn-out GBM material together with the retraction of podocytes out of the tuft and the collapse and hyalinosis of capillaries results in a shrunken tuft that fuses with Bowman's capsule (BC) to glomerular sclerosis. The most frequent pathway to glomerular decay starts with local tuft expansions that result in contacts of structurally intact podocytes to the parietal epithelium initiating the formation of tuft adhesions, which include the penetration of glomerular capillaries into BC. Exudation of plasma from such capillaries into the space between the parietal epithelium and its basement membrane causes the formation of insudative fluid accumulations within BC spreading around the glomerular circumference and, via the glomerulotubular junction, onto the tubule. Degeneration of the corresponding tubule develops secondarily to the glomerular damage, either due to cessation of filtration in cases of global sclerosis or due to encroachment of the insudative spaces. The degenerating tubules induce the proliferation of myofibroblasts resulting in interstitial fibrosis.NEW & NOTEWORTHY Based on analysis of 918 human biopsies, essential derangement in diabetic nephropathy consists of accumulation of worn-out glomerular basement membrane in the mesangium that may advance to global sclerosis. The most frequent pathway to nephron dropout starts with the penetration of glomerular capillaries into Bowman's capsule (BC), delivering an exudate into BC that spreads around the entire glomerular circumference and via the glomerulotubular junction onto the tubule, resulting in glomerular sclerosis and chronic tubulointerstitial damage.


Assuntos
Nefropatias Diabéticas/patologia , Glomerulonefrite/patologia , Néfrons/patologia , Biópsia , Cápsula Glomerular/patologia , Capilares/patologia , Permeabilidade Capilar , Nefropatias Diabéticas/metabolismo , Progressão da Doença , Células Endoteliais/patologia , Fibrose , Membrana Basal Glomerular/patologia , Glomerulonefrite/metabolismo , Humanos , Microscopia Eletrônica de Transmissão , Neovascularização Patológica , Néfrons/metabolismo , Néfrons/ultraestrutura , Podócitos/patologia
10.
Am J Physiol Regul Integr Comp Physiol ; 321(5): R732-R741, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34549626

RESUMO

Although hypertension disrupts the blood-brain barrier (BBB) integrity within the paraventricular nucleus of hypothalamus (PVN) and increases the leakage into the brain parenchyma, exercise training (T) was shown to correct it. Since there is scarce and contradictory information on the mechanism(s) determining hypertension-induced BBB deficit and nothing is known about T-induced improvement, we sought to evaluate the paracellular and transcellular transport across the BBB within the PVN in both conditions. Spontaneously hypertensive rats (SHR) and WKY submitted to 4-wk aerobic T or sedentary (S) protocol were chronically catheterized for hemodynamic recordings at rest and intra-arterial administration of dyes (Rhodamine-dextran 70 kDa + FITC-dextran 10 kDa). Brains were harvesting for FITC leakage examination, qPCR evaluation of different BBB constituents and protein expression of caveolin-1 and claudin-5, the main markers of transcytosis and paracellular transport, respectively. Hypertension was characterized by increased arterial pressure and heart rate, augmented sympathetic modulation of heart and vessels, and reduced cardiac parasympathetic control, marked FITC extravasation into the PVN which was accompanied by increased caveolin-1 gene and protein expression, without changes in claudin-5 and others tight junctions' components. SHR-T vs. SHR-S showed a partial pressure reduction, resting bradycardia, improvement of autonomic control of the circulation simultaneously with correction of both FITC leakage and caveolin-1 expression; there was a significant increase in claudin-5 expression. Caveolin-1 content was strongly correlated with improved autonomic control after exercise. Data indicated that within the PVN the transcytosis is the main mechanism governing both hypertension-induced BBB leakage, as well as the exercise-induced correction.


Assuntos
Barreira Hematoencefálica/metabolismo , Capilares/metabolismo , Permeabilidade Capilar , Caveolina 1/metabolismo , Claudina-5/metabolismo , Terapia por Exercício , Hipertensão/terapia , Núcleo Hipotalâmico Paraventricular/irrigação sanguínea , Condicionamento Físico Animal , Junções Íntimas/metabolismo , Transcitose , Animais , Barreira Hematoencefálica/fisiopatologia , Capilares/fisiopatologia , Sistema Cardiovascular/inervação , Caveolina 1/genética , Claudina-5/genética , Modelos Animais de Doenças , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Esforço Físico , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sistema Nervoso Simpático/fisiopatologia
11.
Nat Protoc ; 16(10): 4564-4610, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34480130

RESUMO

The formation of new blood vessels and the establishment of vascular networks are crucial during brain development, in the adult healthy brain, as well as in various diseases of the central nervous system. Here, we describe a step-by-step protocol for our recently developed method that enables hierarchical imaging and computational analysis of vascular networks in postnatal and adult mouse brains. The different stages of the procedure include resin-based vascular corrosion casting, scanning electron microscopy, synchrotron radiation and desktop microcomputed tomography imaging, and computational network analysis. Combining these methods enables detailed visualization and quantification of the 3D brain vasculature. Network features such as vascular volume fraction, branch point density, vessel diameter, length, tortuosity and directionality as well as extravascular distance can be obtained at any developmental stage from the early postnatal to the adult brain. This approach can be used to provide a detailed morphological atlas of the entire mouse brain vasculature at both the postnatal and the adult stage of development. Our protocol allows the characterization of brain vascular networks separately for capillaries and noncapillaries. The entire protocol, from mouse perfusion to vessel network analysis, takes ~10 d.


Assuntos
Capilares , Microscopia Eletrônica de Varredura , Microtomografia por Raio-X , Animais , Humanos , Imageamento Tridimensional , Camundongos
12.
Medicine (Baltimore) ; 100(35): e27069, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477141

RESUMO

ABSTRACT: To investigate the difference in chorioretinal microcirculation between acute central serous chorioretinopathy (aCSC) and chronic central serous chorioretinopathy (cCSC) using optical coherence tomography angiography.In total, 65 patients previously diagnosed with central serous chorioretinopathy (33 aCSC and 32 cCSC) were included in our cross-sectional study. All patients underwent complete ophthalmologic assessment including logarithm of the minimum angle of resolution best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography angiography. Sixty eyes of 60 refractive error and age matched healthy people were selected as control.The vessel density of inner retina in patients with aCSC were higher than that in patients with cCSC (51.32 ±â€Š2.01 vs 49.15 ±â€Š3.68, P = .004), however, the vessel density of superficial choroid layer in aCSC were significantly lower than that in cCSC (49.83 ±â€Š6.96 vs 53.42 ±â€Š6.28, P = .033). Further analysis of the data reveals the presence of a distinct choroidal neovascularization (CNV) in 8 patients (25%) with cCSC while there was no evidence of CNV in patients with aCSC.Our study can contribute to a better understanding of the difference in retinochoroid microcirculation between aCSC and cCSC. The vessel density of inner retina was lower and the vessel density of superficial choroid was higher in cCSC, and patients with cCSC were more susceptible to CNV than patients with aCSC.


Assuntos
Capilares/fisiopatologia , Coriorretinopatia Serosa Central/classificação , Microcirculação/fisiologia , Adulto , Neovascularização de Coroide/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual/fisiologia
13.
Transl Vis Sci Technol ; 10(9): 5, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34342607

RESUMO

Purpose: To compare optical coherence tomography angiography (OCTA)-derived flux with conventional OCTA measures of retinal vascular density in assessment of physiological changes in retinal blood flow. Methods: Healthy subjects were recruited, and 3 × 3-mm2 fovea-centered scans were acquired using commercially available swept-source OCTA (SS-OCTA) while participants were breathing room air, 100% O2, or 5% CO2. Retinal perfusion was quantified using vessel area density (VAD) and vessel skeleton density (VSD), as well as novel measures of retinal perfusion, vessel area flux (VAF) and vessel skeleton flux (VSF). Flux is proportional to the number of red blood cells moving through a vessel segment per unit time. The percentage change in each measure was compared between the O2 and CO2 gas conditions for images of all vessels (arterioles, venules, and capillaries) and capillary-only images. Statistical significance was determined using paired t-tests and a linear mixed-effects model. Results: Eighty-four OCTA scans from 29 subjects were included (age, 45.9 ± 19.5 years; 14 male, 48.3%). In capillary-only images, the change under the CO2 condition was 168% greater in VAF than in VAD (P = 0.002) and 124% greater in VSF than in VSD (P = 0.004). Similarly, under the O2 condition, the change was 94% greater in VAF than in VAD (P = 0.004) and 57% greater in VSF than in VSD (P = 0.01). Flux measures showed significantly greater change in capillary-only images compared with all-vessels images. Conclusions: OCTA-derived flux measures quantify physiological changes in retinal blood flow at the capillary level with a greater effect size than conventional vessel density measures. Translational Relevance: OCTA-derived flux is a useful measure of subclinical changes in retinal capillary perfusion.


Assuntos
Capilares , Tomografia de Coerência Óptica , Adulto , Idoso , Capilares/diagnóstico por imagem , Angiofluoresceinografia , Fóvea Central , Humanos , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/diagnóstico por imagem
14.
Invest Ophthalmol Vis Sci ; 62(10): 29, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34427622

RESUMO

Purpose: We evaluated a series of fellow eyes (FEs) in patients affected by unilateral idiopathic epiretinal membrane (IERM) with spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCT-A) to determine if a previous defect in the inner retina is present before the mechanical damage to the inner limiting membrane (ILM) caused by posterior vitreous detachment. Methods: In patients with IERM (N = 39), ganglion cell layer (GCL) thickness in FEs was assessed with SD-OCT; in a subgroup (N = 25) the vessel density (VD) at the superficial (SCP) and deep capillary plexus (DCP) was assessed with swept-source OCT-A (SS-OCT-A). These values were then compared with 30 age-matched healthy control eyes (CEs). The statistical analyses used SPSS software version 15.0 (SPSS, Inc., Chicago, IL, USA). Data collected underwent 1-way ANOVA. A level of P < 0.05 was accepted as statistically significant. Results: The GCL thickness in the FEs was significantly lower than in CEs, with a significant thinning in all sectors except temporal ones (mean P < 0.001, superior P = 0.0002, superonasal P < 0.001, inferonasal P < 0.001, and inferior P = 0.002). The VD was significantly lower in the FEs in all sectors of SCP (mean P = 0.009, inner ring P = 0.028, and outer ring P = 0.007). Conclusions: GCL and SCP are significantly reduced in the FEs. These data suggest that a vascular defect in the SCP could cause a cellular loss in the inner retina that may determine the cascade events leading to the IERM proliferation; the diagnosis in a preclinical phase could provide a treatment strategy to prevent the progression of the disease.


Assuntos
Capilares/patologia , Membrana Epirretiniana/patologia , Angiofluoresceinografia/métodos , Macula Lutea/irrigação sanguínea , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Idoso , Membrana Epirretiniana/cirurgia , Feminino , Fundo de Olho , Humanos , Macula Lutea/patologia , Masculino , Estudos Retrospectivos , Vitrectomia/métodos
15.
Med Sci Monit ; 27: e933601, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34456330

RESUMO

BACKGROUND The aim of this study was to investigate distribution rules of radial peripapillary capillaries (RPCs) density and correlations with retinal nerve fiber layers (RNFL) thickness in normal subjects. MATERIAL AND METHODS We included 78 eyes of 78 healthy subjects examined by optical coherence tomography angiography (OCTA). RPCs density and RNFL thickness were measured automatically. Distributions of RPCs density and RNFL thickness were analyzed at different locations. Correlations of these 2 parameters and relationship with large vessels were evaluated by Spearman test. RESULTS Average density for overall, peripapillary, and inside disc RCPs was 56.12±2.51%, 58.56±2.84%, and 60.16±4.01%, respectively. Overall and peripapillary RCPs density were positively correlated with RNFL thickness (r=0.595, P.


Assuntos
Capilares/citologia , Fibras Nervosas/fisiologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/citologia , Adulto , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Campos Visuais , Adulto Jovem
16.
Am J Physiol Renal Physiol ; 321(3): F335-F351, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34338031

RESUMO

Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Caspase-3, an effector responsible for apoptosis execution, is activated within the peritubular capillary (PTC) in the early stage of IRI-induced acute kidney injury (AKI). Recently, we showed that caspase-3-dependent microvascular rarefaction plays a key role in fibrosis development after mild renal IRI. Here, we further characterized the role of caspase-3 in microvascular dysfunction and progressive renal failure in both mild and severe AKI, by performing unilateral renal artery clamping for 30/60 min with contralateral nephrectomy in wild-type (C57BL/6) or caspase-3-/- mice. In both forms of AKI, caspase-3-/- mice showed better long-term outcomes despite worse initial tubular injury. After 3 wk, they showed reduced PTC injury, decreased PTC collagen deposition and α-smooth muscle actin expression, and lower tubular injury scores compared with wild-type animals. Caspase-3-/- mice with severe IRI also showed better preservation of long-term renal function. Intravital imaging and microcomputed tomography revealed preserved PTC permeability and better terminal capillary density in caspase-3-/- mice. Collectively, these results demonstrate the pivotal importance of caspase-3 in regulating long-term renal function after IRI and establish the predominant role of PTC dysfunction as a major contributor to progressive renal dysfunction.NEW & NOTEWORTHY Our findings demonstrate the pivotal importance of caspase-3 in regulating renal microvascular dysfunction, fibrogenesis, and long-term renal impairment after acute kidney injury induced by ischemia-reperfusion injury. Furthermore, this study establishes the predominant role of peritubular capillary integrity as a major contributor to progressive renal dysfunction after ischemia-reperfusion injury.


Assuntos
Injúria Renal Aguda/metabolismo , Caspase 3/metabolismo , Insuficiência Renal Crônica/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Apoptose/fisiologia , Capilares/metabolismo , Feminino , Rim/metabolismo , Camundongos Endogâmicos C57BL , Rarefação Microvascular/patologia , Traumatismo por Reperfusão/patologia
18.
Sensors (Basel) ; 21(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34372187

RESUMO

The moment-based M2M4 signal-to-noise (SNR) estimator was proposed for a complex sinusoidal signal with a deterministic but unknown phase corrupted by additive Gaussian noise by Sekhar and Sreenivas. The authors studied its performances only through numerical examples and concluded that the proposed estimator is asymptotically efficient and exhibits finite sample super-efficiency for some combinations of signal and noise power. In this paper, we derive the analytical asymptotic performances of the proposed M2M4 SNR estimator, and we show that, contrary to what it has been concluded by Sekhar and Sreenivas, the proposed estimator is neither (asymptotically) efficient nor super-efficient. We also show that when dealing with deterministic signals, the covariance matrix needed to derive asymptotic performances must be explicitly derived as its known general form for random signals cannot be extended to deterministic signals. Numerical examples are provided whose results confirm the analytical findings.


Assuntos
Capilares , Ruído , Humanos , Distribuição Normal
19.
Cells ; 10(7)2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34359889

RESUMO

Blocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under-appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34+ VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs' adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.


Assuntos
Túnica Adventícia/patologia , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Células-Tronco/patologia , Animais , Antígenos CD34/metabolismo , Aorta/patologia , Capilares/patologia , Humanos , Camundongos , Modelos Biológicos , Neovascularização Patológica , Neovascularização Fisiológica , Ratos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo
20.
Obesity (Silver Spring) ; 29(9): 1439-1444, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34338418

RESUMO

OBJECTIVE: This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease. METHODS: In this cross-sectional Netherlands Epidemiology of Obesity study, participant sublingual microcirculation was assessed with a newly developed GlycoCheck software (Microvascular Health Solutions Inc., Salt Lake City, Utah), which integrates red blood cell velocity within the smallest capillaries (4-7 µm) and feed vessels (>10 µm). Framingham Risk Score was used to calculate 10-year cardiovascular risk, divided into low-, intermediate-, and high-risk groups. ANOVA was used to evaluate microvascular differences among the groups. RESULTS: A total of 813 participants were included. The high-risk group (n = 168) was characterized by differences in the microvasculature compared with the low-risk group (n = 392): the high-risk group had a 49% reduction in the number of smallest capillaries and a 9.1-µm/s (95% CI: 5.2-12.9) higher red blood cell velocity in the feed vessels. No differences in velocity-corrected perfused boundary regions were found. CONCLUSIONS: It was observed that, with adding red blood cell velocity to the software, sidestream dark field imaging is able to detect microcirculatory differences in a cohort of individuals with obesity at risk for developing cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Capilares , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Humanos , Microcirculação , Obesidade/complicações
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