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1.
Am J Vet Res ; 83(6)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35524960

RESUMO

OBJECTIVE: To evaluate the clinical impact on quantitative analysis of contrast-enhanced ultrasound (CEUS) on single extrahepatic portosystemic shunt (PSS) in dogs. ANIMALS: 21 client-owned dogs with single extrahepatic PSS and 5 healthy Beagles. PROCEDURES: In all dogs, CEUS was performed to calculate the rising time (RT), rising rate (RR), and portal vein-to-hepatic parenchyma transit time (ΔHP-PV) from the time-intensity curve obtained in the hepatic parenchyma and portal vein. All dogs in the PSS group underwent preoperative CT angiography (CTA) and surgery. The CEUS variables in the PSS group were compared with those in the healthy dogs (control group) and were analyzed for shunt types and grades of intrahepatic portal venous branches based on CTA findings, intraoperative portal pressure, and surgical procedures. RESULTS: All 3 CEUS variables showed no significant differences between the PSS and control groups. The RT and ΔHP-PV in the left gastrophrenic shunt group were significantly longer than in the other shunt types. In the intrahepatic portal vascularity, the RT in grade 1 was significantly shorter than in grades 3 and 4, and the RR in grade 1 was significantly higher than in grade 4. The RT and ΔHP-PV were significantly correlated with portal pressure variables. The RT in dogs with partial ligation was significantly shorter than in dogs with complete ligation and percutaneous transvenous coil embolization. CLINICAL RELEVANCE: Quantitative assessments of CEUS may be useful for estimating intrahepatic portal vascularity in dogs with single extrahepatic PSS.


Assuntos
Doenças do Cão , Derivação Portossistêmica Transjugular Intra-Hepática , Animais , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Ligadura/veterinária , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/veterinária , Ultrassonografia/métodos , Ultrassonografia/veterinária
2.
PLoS One ; 17(5): e0266423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511907

RESUMO

PURPOSE: Early detection of microvascular changes in the retina may be important for the risk assessment of cardiovascular health. Therefore, the purpose of this study was to investigate imaging biomarkers in fluorescein angiography (FA) as potential predictors for cardiovascular mortality. METHODS: In this retrospective, matched case-control study, we included FA images from clinical routine data between 2007 and 2018 of 100 patients who died of macrovascular events (Group 1) and 100 age- and sex-matched controls (Group 2). All patients were under treatment for different, mostly retinal, ocular diseases. FA images were used for the measurement of the foveal avascular zone (FAZ) and the arteriolar and venular caliber. RESULTS: Patients mean age on examination day was 69.5 ± 8.3 years with a 1:1 female:male subject ratio. Mean FAZ area of our sample was 0.340 ± 0.135 mm2 for Group 1 and 0.264 ± 0.137 mm2 for Group 2 (P < 0.001), showing a larger FAZ area in patients who subsequently died of macrovascular-related systemic diseases. CONCLUSIONS: Individuals effected by a macrovascular-related disease show a larger FAZ on FA examinations before the event compared to patients which are unaffected. Our results highlight a possible role of the FAZ as additional biomarker for the cardiovascular condition.


Assuntos
Fóvea Central , Doenças Retinianas , Biomarcadores , Estudos de Casos e Controles , Feminino , Angiofluoresceinografia/métodos , Fóvea Central/irrigação sanguínea , Humanos , Masculino , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
3.
PLoS One ; 17(5): e0268005, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35503785

RESUMO

The branches of the porcine subclavian artery are frequently used in endovascular stroke training and research. This study aimed to determine a porcine weight group, in which the arterial diameters most closely match human cerebral artery diameters, and thus optimize the porcine in-vivo model for neuroendovascular purposes. A group of 42 German Landrace swine (45-74 kg) was divided into four subgroups according to their weight. Angiographic images of the swine were used to determine the arterial diameter of the main branches of the subclavian artery: axillary artery, brachial artery, external thoracic artery, subscapular artery (at two different segments), suprascapular artery, caudal circumflex humeral artery, thoracodorsal artery, and circumflex scapular artery. The porcine arterial diameters were correlated with animal weight and compared to luminal diameters of human arteries which are commonly involved in stroke: internal carotid artery, basilar artery, vertebral artery, middle cerebral artery and M2 branches of the middle cerebral artery. Swine weight was positively correlated with porcine arterial diameter. The most conformity with human arterial diameters was found within the two heavier porcine groups (55-74 kg). We suggest the use of swine with a weight between 55-59.7 kg, as lighter animals show less similarity with human arterial diameters and heavier animals could cause more problems with manipulation and handling.


Assuntos
Artéria Axilar , Acidente Vascular Cerebral , Animais , Braço/irrigação sanguínea , Artérias , Humanos , Ombro , Suínos
4.
J Ovarian Res ; 15(1): 56, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538489

RESUMO

Multifaceted functions of the so-called "oncogene" Wip1 have been reported in a previous study, while its actual role remains to be explored in serous ovarian cancer (SOC). In this study, by performing bioinformatic analysis with a public database and immunohistochemical staining of Wip1 in tumour tissue from SOC, we concluded that decreased expression of Wip1 was associated with a higher rate of tumour metastasis and platinum-based therapy resistance and increased ascites volume, which led to poorer prognosis in SOC patients. We also found that overexpression of Wip1 in SKOV3 cells decreased the levels of several cytokines, including VEGF, by secretome profiling analysis, and Wip1 overexpression suppressed angiogenesis both in vitro and in vivo. Mechanistic studies indicated that overexpression of Wip1 decreased the expression of VEGF at both the protein and mRNA levels and that the inhibitory effect was mediated by dephosphorylation of STAT3 at Ser727. Our study uncovered the role of Wip1 in SOC and provides a novel therapeutic strategy for suppressing angiogenesis.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Proteína Fosfatase 2C , Fator de Transcrição STAT3 , Fator A de Crescimento do Endotélio Vascular , Carcinoma Epitelial do Ovário/irrigação sanguínea , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/irrigação sanguínea , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Feminino , Humanos , Neovascularização Patológica/genética , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Indian J Ophthalmol ; 70(5): 1669-1677, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35502048

RESUMO

Purpose: To evaluate the retinal and optic disc microvascular changes according to disease severity in patients with stable chronic obstructive pulmonary disease (COPD), and the correlation of pulmonary parameters with optical coherence tomography angiography (OCTA) findings. Methods: Forty patients with COPD and 30 age- and sex-matched subjects (control group) were included in this cross-sectional prospective study. The COPD group was then divided into two subgroups according to GOLD classification and disease severity as mild-to-moderate COPD group (group 1) and severe COPD group (group 2). OCTA was performed with 6 mm × 6 mm sections for the macula and 4.5 mm × 4.5 mm sections for the optic disc. Foveal retinal thickness (FRT), peripapillary retinal nerve fiber layer (RNFL) thickness, and vessel density in different sections of the retina and optic disc were analyzed. Results: The mean ages, gender, intraocular pressures, peripapillary RNFL thickness, FRT, and optic disc vessel densities were similar among the groups. Compared to the control group and group 1, group 2 showed significantly lower mean foveal vessel density measurements in superficial and deep capillary plexus (P = 0.014 and P = 0.007, respectively). Cigarette packets/year, exacerbation per year, and Modified Medical Research Council showed significant negative correlations, whereas forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity showed significant positive correlations with foveal vessel densities. Conclusion: COPD severity seems to have a negative effect on OCTA measurements. OCTA may reflect the severity of inflammation and hypoxia in COPD and may provide useful detailed information on the role of retinal vascular changes in the follow-up and progression of patients with COPD.


Assuntos
Disco Óptico , Doença Pulmonar Obstrutiva Crônica , Estudos Transversais , Angiofluoresceinografia/métodos , Humanos , Microvasos , Disco Óptico/irrigação sanguínea , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Vasos Retinianos , Tomografia de Coerência Óptica/métodos
6.
Methods Mol Biol ; 2451: 107-125, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35505014

RESUMO

For many decades the chicken embryo chorioallantoic membrane (CAM) has been used for research as an in vivo model in a large number of different fields, including toxicology, bioengineering, and cancer research. More specifically, the CAM is also a suitable and convenient model system in the field of photodynamic therapy (PDT), mainly due to the easy access of its membrane and the possibility of grafting or growing tumors on the membrane and, interestingly, to study the PDT effects on its dense vascular network. In addition, the CAM is simple to handle and cheap. Since the CAM is not innervated until later stages of the embryo development, its use in research is simplified compared to other in vivo models as far as ethical and regulatory issues are concerned. In this review different incubation and drug administration protocols of relevance for PDT are presented. Moreover, data regarding the propagation of light at different wavelengths and CAM development stages are provided. Finally, the effects induced by photobiomodulation on the CAM angiogenesis and its impact on PDT treatment outcome are discussed.


Assuntos
Neoplasias , Fotoquimioterapia , Animais , Embrião de Galinha , Galinhas , Membrana Corioalantoide/irrigação sanguínea , Embrião de Mamíferos
7.
FASEB J ; 36(6): e22339, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35506590

RESUMO

Germinal matrix-intraventricular hemorrhage (GM-IVH) is the most devastating neurological complication in premature infants. GM-IVH usually begins in the GM, a highly vascularized region of the developing brain where glial and neuronal precursors reside underneath the lateral ventricular ependyma. Previous studies using human fetal tissue have suggested increased angiogenesis and paucity of pericytes as key factors contributing to GM-IVH pathogenesis. Yet, despite its relevance, the mechanisms underlying the GM vasculature's susceptibility to hemorrhage remain poorly understood. To gain better understanding on the vascular dynamics of the GM, we performed a comprehensive analysis of the mouse GM vascular endothelium and pericytes during development. We hypothesize that vascular development of the mouse GM will provide a good model for studies of human GM vascularization and provide insights into the role of pericytes in GM-IVH pathogenesis. Our findings show that the mouse GM presents significantly greater vascular area and vascular branching compared to the developing cortex (CTX). Analysis of pericyte coverage showed abundance in PDGFRß-positive and NG2-positive pericyte coverage in the GM similar to the developing CTX. However, we found a paucity in Desmin-positive pericyte coverage of the GM vasculature. Our results underscore the highly angiogenic nature of the GM and reveal that pericytes in the developing mouse GM exhibit distinct phenotypical and likely functional characteristics compared to other brain regions which might contribute to the high susceptibility of the GM vasculature to hemorrhage.


Assuntos
Neovascularização Patológica , Pericitos , Animais , Encéfalo/irrigação sanguínea , Hemorragia Cerebral , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Camundongos , Morfogênese
8.
Chirurgia (Bucur) ; 117(2): 143-153, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35535775

RESUMO

Regardless of the reconstruction surgery used, the fundamental concepts of visceral reconstruction are based on the vascular support needed for the substituting graft. The vascular factor is the main element of any reconstruction technique, as an underlying condition for the visceral material stretch and, along with other factor, for the suture safety. In the case of the stomach, a consistent vascular flow and the minimal vascular anatomy variations are the first theoretical argument. A second argument is based on the intraparietal vascular network features allowing for supplementing visceral perfusion as the blood flow is stopped in one or more pediculi. Graft hypoperfusion is, however, a potential cause of failure, and the most frequently invoked complication is, therefore, a high risk of anastomosis fistulae. A series of modern techniques - arteriography data for the pre-operative vascular reconstruction or Doppler laser fluorometry intraoperative assessments, graft oximetry, laser speckle (spot) scan or the use of indocyanine green staining (ICG) - represent methods of early determination of the gastric graft perfusion/microperfusion quality used in reducing such risks. The doubts regarding the gastric perfusion mandate the use of vascular augmentation techniques. If such techniques are not used, the final outcome is uncertain and difficult to correct.


Assuntos
Esofagectomia , Esofagoplastia , Esofagectomia/métodos , Humanos , Verde de Indocianina , Estômago/irrigação sanguínea , Estômago/cirurgia , Resultado do Tratamento
9.
Ann Plast Surg ; 88(3 Suppl 3): S235-S238, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35513326

RESUMO

PURPOSE: Our previous rodent studies demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. Histologically, we found that topical tacrolimus was correlated with increased vascular growth in areas more susceptible to ischemic damage. The purpose of this study was to investigate the potential benefits of pretreatment with tacrolimus. By applying tacrolimus in advance of raising the dorsal skin flaps, we hoped to increase vascularity and thus increase the overall viability of the flaps. METHODS: Twenty Sprague-Dawley rats were initially randomized to 4 groups based on timing of tacrolimus treatment (presurgical/postsurgical treatment): control/control (C/C), control/tacrolimus (C/T), tacrolimus/control (T/C), and tacrolimus/tacrolimus (T/T). Treatments consisted of 0.2 g of the control (topical petroleum jelly) and 0.1% topical tacrolimus to the rat dorsum twice per day. After 7 days of presurgical treatment, a cranially based dorsal skin flap measuring 3 × 10 cm was created. Two rats perished during surgery and were excluded for further analysis. Each rat was treated for a further 7 days and sacrificed. Two blinded reviewers marked the total skin flap area as well as areas of viable tissue, reversible ischemia, and full-thickness necrosis. Percentage areas were calculated using Fiji/ImageJ, and statistical analysis was performed in R. RESULTS: The average viable areas for C/C, C/T, T/C, and T/T were 31.4%, 31.9%, 35.6%, and 22.6%, respectively. The average reversible ischemic area for C/C, C/T, T/C, and T/T was 53.1%, 54.0%, 54.1%, and 71.5%, respectively. The average necrotic area for C/C, C/T, T/C, and T/T was 15.4%, 14.0%, 10.2%, and 5.9%, respectively. For areas of reversible ischemia, T/T arm had higher areas compared with C/T (P = 0.004) and T/C (P = 0.044). There was no significance between treatment arms for areas of viable and necrotic tissue. CONCLUSIONS: We observed higher areas of reversible ischemia for continuous tacrolimus treatment compared with only pre-tacrolimus application or post-tacrolimus application. This suggests that tacrolimus application before and after surgical insult may be associated with improved ischemic survival of the skin. Although we did not observe decreased areas of necrosis for tacrolimus treatment compared with control, this was likely due to the limited number of rats available in each arm to reach significance. Further study is needed to fully elucidate the encouraging trends that were observed.


Assuntos
Lesões dos Tecidos Moles , Tacrolimo , Animais , Sobrevivência de Enxerto , Humanos , Isquemia , Necrose , Vaselina , Projetos Piloto , Ratos , Ratos Sprague-Dawley , Retalhos Cirúrgicos/irrigação sanguínea , Tacrolimo/farmacologia
10.
Nat Neurosci ; 25(5): 567-576, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35501382

RESUMO

Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues facilitate intersystem communication. Cerebrospinal fluid (CSF), which interfaces with the glymphatic system and thereby drains the brain's interstitial and perivascular spaces, facilitates outward signaling beyond the blood-brain barrier. In the present study, we report that CSF can exit into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice migrate along perivascular spaces of dural blood vessels and then travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria hijack this route to invade the skull's hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. As skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in CSF by regional marrow may have broad implications for inflammatory neurological disorders.


Assuntos
Sistema Glinfático , Meningites Bacterianas , Animais , Medula Óssea , Encéfalo/irrigação sanguínea , Líquido Cefalorraquidiano , Sistema Glinfático/fisiologia , Hematopoese , Camundongos , Crânio
11.
Tidsskr Nor Laegeforen ; 142(7)2022 05 03.
Artigo em Norueguês | MEDLINE | ID: mdl-35510451

RESUMO

BACKGROUND: Breast reconstruction using free flaps based on the lower abdominal tissue is a common procedure. Postoperatively, the blood supply and innervation of the flap will be altered due to denervation. The case presented here illustrates the resulting increased sensitivity to heat exposure. CASE PRESENTATION: A woman in her sixties was treated for right-sided breast cancer with mastectomy and autologous reconstruction using a deep inferior epigastric perforator (DIEP) flap. Fourteen years later she experienced a dermal and subcutaneous burn in the flap after sunbathing for three hours wearing a black bikini. The burn injury required surgical treatment including debridement and skin transplantation. INTERPRETATION: Postoperative denervation resulting in altered thermoregulatory mechanisms and reduced sensation of a free flap can increase the risk of thermal damage long after surgery. Lifelong preventive measures might therefore be necessary. Patients and medical professionals need to be aware of this hazard after reconstructive surgery using free flaps.


Assuntos
Neoplasias da Mama , Queimaduras , Mamoplastia , Retalho Perfurante , Neoplasias da Mama/cirurgia , Queimaduras/etiologia , Queimaduras/cirurgia , Artérias Epigástricas/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Mastectomia/efeitos adversos , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/cirurgia , Estudos Retrospectivos
12.
Sci Rep ; 12(1): 7104, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501327

RESUMO

Due to excessive elongation of the eyeball, myopia-related vascular abnormalities are frequently observed in the central retinal artery (CRA) and its intraretinal branches. In addition to inconsistency in previously reported findings, hemodynamic (reduced flow velocity, increased vascular resistance) and morphological changes (narrower vessel diameter) were usually studied separately. This cross-sectional study evaluated the hemodynamic and morphological characteristics concurrently in a large sample of healthy myopes, by using the color Doppler ultrasound and adaptive optics retinal camera. Results showed that the retrobulbar segment of CRA had a tendency of slightly reduced flow velocity in eyeballs with longer axial length, but the correlation was not significant after adjusting for the multiple correlations. Vascular resistance was not affected by the axial elongation. With respect to the intraretinal branches, no significant changes in longer eyes of total diameter or lumen diameter were observed, while both the wall thickness and the wall cross-sectional area were significantly increased, but only a marginally increase in the wall to lumen ratio was found with increasing axial length. This implies some potential small artery remodeling in the intraretinal CRA branches. Overall, blood supply of the inner retina in healthy young myopes is likely to be maintained. Additionally, morphological parameters of vascular microstructure could be potential biomarkers to monitor myopia progression and understand myopia-related vascular abnormalities in future studies.


Assuntos
Miopia , Artéria Retiniana , Estudos Transversais , Olho/irrigação sanguínea , Olho/diagnóstico por imagem , Hemodinâmica , Humanos , Miopia/diagnóstico por imagem , Artéria Retiniana/diagnóstico por imagem
13.
Acta Chir Belg ; 122(3): 215-221, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35499197

RESUMO

BACKGROUND: Pedicle length deficiency in microsurgical procedure is a challenging issue. The aim of this report is to present a case series of a flap-splitting technique for pedicle lengthening of large multiple perforator-based (MPB) free flaps. METHODS: In this retrospective case series, we reviewed the medical records of patients who underwent free flap repair with "split flap" pedicle-lengthening technique between August 2017 and December 2021. Main outcome measures included patient demographics, indications, defect size, flap type, additional vascular pedicle length, and flap survival. RESULTS: Data from 16 patients (age 38-78 years) were reviewed. Indications included breast reconstruction, repair of scalp malignancy or titanium mesh implant exposure, and repair of burn scar contracture. Flaps included ALT flap, LD flap and DIEP flap. The mean added pedicle length was 3.8 cm. Fifteen flaps survived completely and one flap was necrotic distally. No major complications occurred. CONCLUSIONS: The 'split flap' technique could be an effective remedy for unexpected pedicle length deficiencies in large MPB free flaps.


Assuntos
Contratura , Retalhos de Tecido Biológico , Mamoplastia , Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Adulto , Idoso , Contratura/etiologia , Retalhos de Tecido Biológico/cirurgia , Humanos , Mamoplastia/métodos , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Procedimentos Cirúrgicos Reconstrutivos/métodos , Estudos Retrospectivos
14.
BMC Surg ; 22(1): 170, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538458

RESUMO

BACKGROUND: Laparoscopic surgery for cancer located in the transverse colon or splenic flexure is difficult because of vascular variability in this region and adjacent vital organs such as the pancreas, spleen, and duodenum. METHODS: This retrospective cohort study involved 51 patients who underwent laparoscopic surgery for colon cancer at Tokushima University Hospital from July 2015 to December 2020. Variations of the middle colic artery (MCA), left colic artery (LCA), middle colic vein (MCV), and first jejunal vein (FJV) and short-term outcomes of laparoscopic surgery in patients with each vascular variation were evaluated. RESULTS: Variations of the MCA, LCA, MCV, and FJV were classified into four, three, five, and three patterns, respectively. The short-term outcomes of laparoscopic surgery for transverse colon cancer in patients with MCA variations and those with FJV variations were evaluated, and no significant difference was found in the operation time, blood loss, postoperative complication rate, time from surgery to start of dietary intake, or time from surgery to discharge among the different variations. Additionally, no significant differences were found in the short-term outcomes of laparoscopic surgery for descending colon cancer in patients with LCA variations. CONCLUSION: Preoperative assessment of vascular variations may contribute to the stability of short-term outcomes of laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer.


Assuntos
Colo Transverso , Neoplasias do Colo , Laparoscopia , Colectomia , Colo Descendente/cirurgia , Colo Transverso/irrigação sanguínea , Colo Transverso/cirurgia , Neoplasias do Colo/cirurgia , Humanos , Estudos Retrospectivos
15.
Mol Cancer ; 21(1): 111, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538475

RESUMO

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.


Assuntos
Adenosina , Carcinoma de Células Renais , Neoplasias Renais , Metiltransferases , Sunitinibe , Fator 1 Associado a Receptor de TNF , Adenosina/análogos & derivados , Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Metiltransferases/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Sunitinibe/farmacologia , Fator 1 Associado a Receptor de TNF/genética , Fator 1 Associado a Receptor de TNF/metabolismo
16.
Physiol Rep ; 10(8): e15256, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35439367

RESUMO

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho-excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end-inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post-exercise circulatory occlusion (SHG + PECO; measured in the non-exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho-excitation, but in a reflex-dependent manner.


Assuntos
Antebraço , Força da Mão , Pressão Sanguínea/fisiologia , Antebraço/irrigação sanguínea , Força da Mão/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Sistema Nervoso Simpático/fisiologia , Resistência Vascular
17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(4): 446-450, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35426284

RESUMO

Objective: To explore the feasibility of peroneal perforating chimeric tissue flap in repairing the composite defects of calf and heel based on lower limb angiography, and the clinical effect. Methods: The digital subtraction angiography images of lower limbs of 50 patients met the selection criteria between May 2011 and October 2014 were used as the research object to observe the course of peroneal artery and its perforating vessels. Based on the observation results, between April 2015 and October 2020, the peroneal perforating chimeric tissue flap was designed to repair 7 cases of composite defects of the calf and heel. There were 5 males and 2 females with an average age of 38 years (range, 25-55 years). The causes of injury included traffic accident in 4 cases, falling from height in 2 cases, and machine strangulation in 1 case. There were 5 cases of calf skin defect and tibial defect. The size of skin defect ranged from 5 cm×3 cm to 11 cm×7 cm, and the length of bone defect was 5-8 cm. There were 2 cases of heel skin defect and calcaneal defect. The sizes of skin defects were 5.0 cm×4.0 cm and 7.5 cm×6.5 cm, and the bone defects were 3.0 cm×2.6 cm and 4.0 cm× 3.0 cm. For the calf defect, the size of skin flap ranged from 6 cm×4 cm to 12 cm×8 cm, and the length of the fibula was the same as that of the tibial defect. For the heel defect, the sizes of the skin flaps were 8.5 cm×5.5 cm and 13.0 cm×5.0 cm, and the lengths of the fibulae were 10 cm and 12 cm. Free transplantation was performed in 5 cases and pedicle transplantation in 2 cases. The wound at donor site was repaired with skin grafting or sutured directly. Results: The peroneal artery ran close to the fibula 7.25-8.40 cm below the fibula head and send out 5-7 perforating vessels, with an average of 6.5 vessels. Perforating vessels mainly appeared in four places, which were (9.75±0.91), (13.21±0.74), (18.15±1.22), and (21.40±0.75) cm below the fibular head, with the occurrence rates of 94%, 90%, 96%, and 88%, respectively. Clinical application of 7 cases of peroneal perforating chimeric tissue flap all survived, all wounds healed by first intention. The skin graft at donor site survived and the incision healed by first intention. All patients were followed up 6-36 months, with an average of 12 months. Peroneal perforator chimeric tissue flap had good shape and soft texture. X-ray films showed that the bone graft healed well, and the healing time was 6-11 months (mean, 7 months). No obvious bone resorption was observed during follow-up. Five patients had no pain when walking, and 1 had mild pain with claudication. Postoperative heel ulcers formed in 1 case and healed after wearing custom plantar pressure dispersing shoes. At 6 months after operation, 2 patients were rated as grade Ⅳ and 5 patients as grade Ⅴ according to Holden walking function score. Conclusion: The peroneal perforating vessel distribution is constant and the peroneal perforating chimeric tissue flap is safe and reliable for repairing the composite defects of calf and heel.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles , Adulto , Feminino , Humanos , Masculino , Retalho Perfurante/irrigação sanguínea , Procedimentos Cirúrgicos Reconstrutivos/métodos , Transplante de Pele , Lesões dos Tecidos Moles/diagnóstico por imagem , Lesões dos Tecidos Moles/cirurgia , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/cirurgia , Resultado do Tratamento
18.
J Vis Exp ; (182)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35435911

RESUMO

Autologous arteriovenous fistula (AVF) is the primary and best option to obtain vascular access for hemodialysis treatment; other options are arteriovenous graft (AVG) and central venous catheterization (CVC). The implementation of radio-cephalic autologous arteriovenous fistula (RC-AVF) in the forearm was preferred among patients with superior vascular conditions. However, there is a high rate of early fistula failure. The chosen surgical method is understood to have an effect on the maturation of the fistula. New surgical procedures such as radial artery deviation and reimplantation (RADAR) have been significantly improved for juxta-anastomotic stenosis. Nevertheless, new problems such as stenosis of arteries and narrowing of surgical indication were also found. In this report, we presented a modified no-touch technique (MNTT) to create an RC-AVF, in which the venous and arterial wall avoid devascularization and the radial artery does not sever.


Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/cirurgia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/métodos , Constrição Patológica , Antebraço/irrigação sanguínea , Antebraço/cirurgia , Humanos , Diálise Renal/métodos , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular
19.
BMJ Case Rep ; 15(3)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361669

RESUMO

Isolated deep cerebral venous thrombosis (CVT), especially involving only the right thalamus, is one of the rarest forms of intracranial venous thrombosis in a child. The anatomy and flow patterns of the deep cerebral venous system are complex and usually, the thrombosis of the internal cerebral veins (ICV) results in thalamic infarction bilaterally. The focal infections, thalamic tumours and vascular malformations may have overlapping clinicoradiological patterns. The treating team should be able to recognise the atypical phenotypes of the deep CVT at the earliest, which can facilitate apt treatment and obviate the need for unnecessary investigations and interventions. We present a rare case of an isolated right thalamic acute venous infarct secondary to bilateral ICV thrombosis in a toddler who was successfully managed by timely diagnosis and with only conservative therapy.


Assuntos
Veias Cerebrais , Trombose Intracraniana , Trombose Venosa , Infarto Cerebral/complicações , Veias Cerebrais/patologia , Pré-Escolar , Humanos , Trombose Intracraniana/complicações , Tálamo/irrigação sanguínea , Tálamo/diagnóstico por imagem , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem
20.
Sci Rep ; 12(1): 6718, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468922

RESUMO

Myocardial injury after non-cardiac surgery (MINS) is common. We investigated the incidence and outcomes of MINS, and mechanistic underpinnings using pre-operative whole blood gene expression profiling in a prospective cohort study of individuals undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD). Major adverse cardiovascular and limb events (MACLE) were defined as a composite of death, myocardial infarction, stroke, major lower extremity amputation or reoperation. Among 226 participants undergoing LER, MINS occurred in 53 (23.5%). Patients with MINS had a greater incidence of major adverse cardiovascular events (49.1% vs. 22.0%, adjusted HR 1.87, 95% CI 1.07-3.26) and MACLE (67.9% vs. 44.5%; adjusted HR 1.66, 95% CI 1.08-2.55) at median 20-month follow-up. Pre-operative whole blood transcriptome profiling of a nested matched MINS case-control cohort (n = 41) identified upregulation of pathways related to platelet alpha granules and coagulation in patients who subsequently developed MINS. Thrombospondin 1 (THBS1) mRNA expression was 60% higher at baseline in patients who later developed MINS, and was independently associated with long-term cardiovascular events in the Duke Catheterization Genetics biorepository cohort. In conclusion, pre-operative THBS1 mRNA expression is higher in patients who subsequently develop MINS and is associated with incident cardiovascular events. Pathways related to platelet activity and coagulation associated with MINS provide novel insights into mechanisms of myocardial injury.


Assuntos
Doença Arterial Periférica , Transcriptoma , Humanos , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/genética , Doença Arterial Periférica/cirurgia , Estudos Prospectivos , RNA Mensageiro , Fatores de Risco
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