Deciphering Key microRNA Regulated Pathways in Tissue-Engineered Blood Vessels: Implications for Vascular Scaffold Production.

MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle.

Vascular smooth muscle cells exhibit elevated hypoxia-inducible Factor-1α expression in human blood vessel organoids, influencing osteogenic performance.

Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.

Nefropatía por IgA con microangiopatía trombótica / IgA nephropathy with thrombotic microangiopathy

INTRODUCTION: IgA nephropathy is the most common glomerulopathy in the world, it has a wide clinical expression, from asymptomatic to rapidly progressive glomerulonephritis. The definitive diagnosis is renal biopsy, within which the IgA pattern can be identified, including thrombotic microangiopathy. CLINICAL CASE: 28-year-old female patient, with a history of preeclampsia in the last pregnancy, presents high blood pressure, hematuria and proteinuria. Study begins with initially negative results. Renal biopsy confirms IgA nephropathy with thrombotic microangiopathy. DISCUSSION: Vascular damage is underestimated in IgA nephropathy. Thrombotic microangiopathy can be associated with various clinical manifestations, however when it is associated with IgA Nephropathy it is usually associated with proteinuria, arterial hypertension and elevation of creatinine. In the presence of microangiopathy, secondary causes must be ruled out. In general, there is no pathognomonic serological marker. Eventually patients could benefit from the use of eculizumab. CONCLUSION: IgA nephropathy is the most common glomerulopathy worldwide; there is a wide range of clinical presentations, among which thrombotic microangiopathy can be found. This presentation is associated with a higher risk of progression to end-stage renal disease.

INTRODUCCIÓN: La nefropatía por IgA es la glomerulopatía más frecuente en el mundo, tiene una amplia expresión clínica, desde asintomática hasta glomerulonefritis rápidamente progresivas. El diagnóstico definitivo es la biopsia renal, dentro de las cuales se puede identificar el patrón de la IgA, dentro de los cuales está la microangiopatía trombótica. CASO CLÍNICO: Paciente femenina 28 años, con antecedentes de preeclampsia en último embarazo, presenta hipertensión arterial, hematuria y proteinuria. Se inicia estudio con resultados inicialmente negativos. Biopsia renal confirma nefropatía por IgA con microangiopatía trombótica. DISCUSIÓN: En la nefropatía por IgA se subestima el daño vascular. La microangiopatía trombótica se puede asociar con varias manifestaciones clínicas, sin embargo, cuando está asociada a NIgA suele estar asociado con proteinuria, hipertensión arterial y elevación y creatinina. Ante la presencia de microangiopatía, se deben descartar causas secundarias de la misma. En general no existe un marcador serológico patognomónico. Eventualmente los pacientes se podrían beneficiar del uso de eculizumab. CONCLUSIÓN: La nefropatía por IgA es la glomerulopatía más frecuente a nivel mundial, existe una gran gama de presentaciones clínicas, dentro de las cuales se puede encontrar microangiopatía trombótica. Esta última presentación se asocia con mayor riesgo de progresión a enfermedad renal en etapa terminal.

Capítulo13: sistema vascular circulación anterior / Chapter 13: Vascular system anterior circulation

Dos fenómenos, la vasculogénesis y la angiogénesis, contribuyen al desarrollo y crecimiento de los vasos sanguíneos. La vasculogénesis representa la formación de nuevos vasos, a partir de células precursoras (angioblastos), mientras que la angiogénesis hace mención a la formación de nuevos vasos, a partir de elementos vasculares preexistentes.

Median nerve compression at elbow level by a proximal cubital artery pseudoaneurysm: a case report

We describe the case of an 82-year-old man who had recently undergone cardiac surgery (quadruple coronary bypass), who consulted due to the appearance of a necrotic eschar on the thumb of the right index finger, together with paraesthesia and hypoaesthesia in the first 3 fingers of the same hand. An ultrasound scan of the right elbow was performed to rule out involvement of the median nerve and an anechoic, thick-walled mass was found, dependent on the wall of the proximal ulnar artery, compatible with a pseudoaneurysm of the same, compressing the nerve. Electromyography showed an acute lesion of the proximal median nerve and angio-CT confirmed the diagnosis of pseudoaneurysm of the proximal ulnar artery. Pseudoaneurysm is a dilatation by rupture of the arterial wall, which does not involve all three layers of the arterial wall and communicates with the vascular lumen. Its development after vascular manipulation is very rare, and it is uncommon for it to act by compressing a nerve structure. In our case, together with vascular surgery, treatment with intralesional thrombin was decided, with good evolution.

Se describe el caso de un varón de 82 arios intervenido recientemente de cirugía cardíaca (cuádruple bypass coronario), que consulta por aparición de una escara necrótica en el pulpejo del dedo índice derecho, junto a parestesias e hipoestesias en los tres primeros dedos de dicha mano. Se realiza una ecografía del codo derecho para descartar afectación del nervio mediano y se objetiva una masa anecoica, de paredes engrosadas, dependientes de la pared de la arteria cubital proximal, compatible con pseudoaneurisma de esta, que comprime dicho nervio. En la electromiografía se evidencia una lesión aguda del nervio mediano a nivel proximal y en el angio-TC se confirma el diagnóstico de pseudoaneurisma de la arteria cubital proximal. El pseudoaneurisma es una dilatación por rotura de la pared arterial, que no implica a las tres capas de esta y se comunica con la luz vascular. Su desarrollo tras una manipulación vascular es muy infrecuente y que actúe comprimiendo una estructura nerviosa es poco común. En nuestro caso, conjuntamente con cirugía vascular se decidió tratamiento con trombina intralesional, con buena evolución.

Variaciones morfológicas de la glándula submandibular en ratas obesas por acción de glutamato monosódico / Morphological variations of the submandibular gland in obese rats by the action of monosodium glutamate

Este estudio tuvo como objetivo demostrar la existencia de variaciones morfológicas en el tejido conectivo de la glándula submandibular de ratas obesas expuestas a glutamato monosódico (GMS). Se utilizaron 12 ratas Sprague Dawley machos recién nacidas (6 ratas para el grupo 1, control; 6 ratas para el grupo 2 (GMS), 4 mg/g de glutamato monosódico de peso (5 dosis) mantenidas por 16 semanas respectivamente con una dieta y agua ad libitum. En el estudio se realizó un análisis estereológico e histológico, demostrándose una variación en el tejido conectivo presentando una disminución del volúmen glandular, mayor fibrosis, y disminución de adipocitos a nivel periférico siendo reemplazado por tejido rico en colágeno. Los vasos sanguíneos observados a nivel estereológico no presentan mayores cambios en cuanto a volumen, superficie y área.

SUMMARY: This study aims to demonstrate the existence of morphological variations in the connective tissue of the submandibular gland of obese rats exposed to MSG. Twelve male newborn Sprague Dawley rats were used (6 rats for group 1, control; 6 rats for group 2 (MSG), 4 mg/g of monosodium glutamate of weight (5 doses) maintained for 16 weeks respectively with a diet and water ad libitum. In the study, a stereological and histological analysis was carried out, demonstrating a variation in the connective tissue, presenting a decrease in the glandular volume, greater fibrosis, and a decrease in adipocytes at the peripheral level, being replaced by tissue rich in collagen. Blood cells observed at the stereological level do not present major changes in terms of volume, surface and area, but in the histological study greater vascularization is observed.

Caudal vena cava thrombosis in cows

Background: Caudal vena cava thrombosis (CVCT) is a serious disease that affects cattle. Due to being commonly a fatal pathology, it causes economic losses for producers and national livestock. Thus, the present study describes the epidemiological, clinical, ultrasonographic imaging and pathological findings in 4 cattle with CVCT attended at the Veterinary Hospital (HV) of the Institute of Veterinary Medicine (IMV) of the Federal University of Pará (UFPA). Cases: The animals were crossbreds of the Gir x Holstein and Jersey x Holstein breeds, aged between 4 and 8 years old, raised in semi-extensive and intensive systems. The main clinical signs were pale mucous membranes, reluctance to move, markedly positive venous pulse, engorged jugular with positive stasis test, and serous to mucopurulent nasal exudation. The auscultation of the lung fields revealed tachypnea, silent areas, wheezing, and pleural friction, in addition to coughing, expiratory dyspnea, mouth breathing, and expiratory grunts. One animal had severe hemoptysis. The ultrasound examination performed on a bovine revealed a circular and dilated caudal vena cava in cross-section. Laboratory tests in 3 cattle revealed anemia, leukocytosis with neutrophil left shift, and increased liver enzymes. At necropsy, all cattle had thrombi in the hepatic segment of the caudal vena cava. In the lung, multiple abscesses and areas of parenchymal consolidation, crateriform areas, as well as thrombi in the arteries were observed. Pleural effusion and ascites were seen in all cattle. Clotted blood was seen in the trachea, bronchi, and on rumen contents of an animal. Histopathological alterations seen in the liver were centrilobular hepatocytes with frequent intensely eosinophilic cytoplasm, and pyknotic, karyorrhexic, or absent nuclei and cell borders barely distinguishable. In the lung were nodular and random formations, with a thick wall of mature connective tissue and a central area full of cellular debris, necrotic cells, and intact and degenerated neutrophils (abscesses). Discussion: The set of diagnostic tools that include epidemiology, clinical signs and clinical examinations, ultrasound, necropsy, and histopathology were efficient in the diagnosis of CVCT. The possible causes that led the animals to develop CVCT were diffuse septic pododermatitis in the medial nail of the right pelvic limb associated with traumatic reticuloabomasitis and liver abscesses. In 1 cow, it was not possible to establish the probable cause of CVCT, but for the other cattle in the present study, the probable causes are in agreement with studies that have shown that this disease can occur as a sequel to several septic conditions such as jugular phlebitis, mastitis, hoof rot, enteritis, pneumonia, traumatic reticulopericarditis, acidosis and rumen laminitis, as well as omphalophlebitis in calves. The tachypnea, serous to purulent nasal exudation, pulmonary wheezing, pleural friction, coughing, and expiratory dyspnea, usually with open mouth breathing and expiratory grunts evidenced in the animals of this study, occurred as a result of embolic abscess pneumonia. The presence of multiple lung abscesses, areas of parenchymal consolidation, crateriform foci, and thrombi in the pulmonary arteries and chronic suppurative pneumonia, found at necropsy of the animals in the present study, are related to the development of a thrombus in the caudal vena cava that detaches and embolizes and lodges in the pulmonary arteries. The histopathological findings in 1 cow are compatible with lesions found at necropsy and draw attention to embolic pneumonia and liver lesions, which, are related to thrombi in pulmonary arteries and abscesses formed from CVCT, as well as venous stasis exerted in the return circulation.

SANT esplénico: tumoración infrecuente / Splenic SANT: Uncommon tumor

La Transformación Nodular Angiomatoide Esclerosante del bazo (SANT) es una patología poco común, que afecta a vasos sanguíneos de forma benigna con esclerosis extensa de la pulpa roja. Paciente masculino, 24 años, consulta en centro privado (Paraguay) por un cuadro de 7 meses de evolución de disnea paroxística y sudoración fría. Al examen físico y laboratorial sin datos de valor. La ecografía abdominal demuestra bazo con parénquima inhomogéneo con imagen pseudonodular 48x41 mm de diámetro, la RMN con contraste confirma hallazgo por nódulo irregular, con realce que predomina en la periferia de la fase arterial, con aspecto radiado y relleno centrípeto en fase venosa y tardía, la histopatología confirma diagnóstico clínico-imagenológico de SANT. Esta tumoración es frecuente entre los 45 a 48 años, manifestada con esplenomegalia, poca sintomatología, llama la atención la presentación del caso que se contrapone con la bibliografía. Considerando la falta de métodos auxiliares para descartar la malignidad, se aplica esplenectomía como conducta terapéutica.

Nodular Angiomatoid Sclerosing Transformation of the Spleen (SANT) is a rare pathology, which affects blood vessels benignly with extensive sclerosis of the red pulp. A 24-year-old man consulted in a private center (Paraguay) for a 7-month course of paroxysmal dyspnea and cold sweating. Physical examination and laboratory evaluation show no abnormalities. Abdominal ultrasound shows a spleen with heterogeneous parenchyma and a pseudonodular image that is 48mm x 41mm in diameter. Contrasted MRI confirms the finding of an irregular nodule, with enhancement that predominates in the periphery of the arterial phase, with radiated appearance and centripetal filling in venous and late phase. Histopathology confirms diagnosis of SANT. SANT is frequent between 45 and 48 years of age, manifested with splenomegaly and scarce symptomatology. The presentation of this case differs with literature. Considering the lack of auxiliary methods to rule out malignancy, a splenectomy is performed.

Experiencia inicial de un equipo multidisciplinario para el manejo de anomalías vasculares complejas / Initial experience of a multidisciplinary approach for the management of complex vascular anomalies

Introducción: Las anomalías vasculares (AV) están constituidas por un amplio espectro de alteraciones en los vasos sanguíneos y linfáticos, incluidos los tumores y las malformaciones vasculares. El objetivo del presente estudio fue describir la experiencia inicial de un grupo multidisciplinario para el manejo de las anomalías vasculares complejas en pacientes pediátricos en un hospital de tercer nivel. Metodología: El presente estudio observacional de pacientes pediátricos, presentados y analizados en un grupo de anomalías vasculares en Ecuador, desde noviembre de 2019 hasta mayo de 2022. Se recopilaron los diagnósticos según la clasificación de la Sociedad Internacional para el Estudio de las Anomalías Vasculares, localización de la lesión, trata-miento ofrecido, complicaciones y evolución; se excluyeron los pacientes con hemangioma infantil no complicado y hemangioma congénito. Resultados: Se incluyeron 45 pacientes con anomalías vasculares de los cuales, 53% fueron femenino y 47% masculino. La edad promedio al momento de la presentación fue de 5.9 años, un 78% tenían malformaciones vasculares y 22% tenían tumores vasculares. Las mal-formaciones vasculares de tipo venosa fueron las más frecuentes con un 22%. La malformación más frecuente fue venosa en cabeza/cara (29%) y linfáticas (16%). El 89% de los pacientes presentaron por lo menos un síntoma y el tratamiento más usado fue la escleroterapia en un 36.36%. Conclusión: Es el primer reporte realizado en Ecuador de un equipo multidisciplinario que atiende AV complejas en niños según la bibliografía revisada, afirmando que las AV son un gran reto debido al amplio espectro de patologías que las conforman. El equipo multidisciplinario garantiza el manejo completo en los casos de AV complejo logrando un adecuado diagnóstico, para así ofrecer las mejores opciones terapéuticas para el paciente pediátrico.

Introduction: Vascular Anomalies (VA) are constituted by a wide spectrum of alterations, including tumors and vascular malformations, pediatric patients with vascular anomalies will usually benefit from the contributions made by a multidisciplinary team approach. The aim of this study was to describe the initial experience of a multidisciplinary approach group for the management of complex vascular anomalies in pediatric patients. Methodology: This observational study of pediatric patients (< 18 years), presented and analyzed in a group of vascular anomalies in Ecuador, from November 2019 to May 2022. Diagnoses were compiled according to the classification of the Society International for the Study of Vascular Anomalies, location of the lesion, treatment offered, complications and evolution; patients with uncomplicated infantile hemangioma and congenital hemangioma were excluded. Results: A total of 45 patients with vascular anomalies were included, of which 53% were female and 47% male. The mean age at presentation was 5.93 years, 78% had vascular malformations, and 22% had vascular tumors. Venous vascular malformations were the most frequent with 22% and lymphatic malformations 16%. The most frequent location was head/face affected by venous-type vascular malformations with 29%. At least one symptom was present in 89% of the patients, the most used treat-ment was sclerotherapy in 36.36%. Conclusión: It is the first report made in Ecuador of a multidisciplinary team that treats complex VA in children according to the reviewed bibliography, affirming that VA are a great challenge due to the wide spectrum of pathologies that comprise them. The multidisciplinary team guarantees complete management in complex VA cases, achieving an adequate diagnosis, in order to offer the best therapeutic options for the pediatric patient.

Escleroterapia no tratamento de lesões vasculares orais / Escleroterapia en el tratamiento de las lesiones vasculares orales / Sclerotherapy in the treatment of oral vascular injuries

Objetivo: apresentar um caso de lesão vascular em paciente idoso tratado pela técnica da escleroterapia. Relato do caso: paciente masculino, 67 anos, vítima de acidente vascular cerebral, buscou atendimento odontológico por apresentar raízes residuais. Durante o exame físico foi identificada lesão exofítica, de coloração violácea, base séssil, com aproximadamente dois centímetros, localizada em comissura labial esquerda. Para confirmar a origem da alteração foi realizada manobra semiotécnica (diascopia) que revelou tratar-se de lesão vascular. Por ser o paciente idoso, hipertenso, com histórico de acidente vascular cerebral, foi feita a opção por tratamento conservador, sendo realizada a escleroterapia com oleato de monoetanolamina 5%, numa única sessão. No retorno de sete dias, foi observada regressão parcial da lesão e com 30 dias a região se mostrou completamente cicatrizada, sem vestígios da alteração. O oleato de monoetanolamina provoca uma reação inflamatória estéril, aguda, dose-dependente, no endotélio vascular e nos tecidos extravasculares que resulta em fibrose e obliteração dos vasos sanguíneos, induzindo a regressão das lesões. Conclusão: Com base no caso apresentado e nos registros da literatura é possível afirmar que a escleroterapia é uma alternativa terapêutica minimamente invasiva, eficaz, de baixo custo e com resultado estético favorável no tratamento de lesões vasculares orais... (AU)

Objective: to present a case of vascular injury in an elderly patient treated by the sclerotherapy technique. Case report: male patient, 67 years old, victim of a stroke, sought dental care due to residual dental roots. During the physical examination, an exophytic lesion, violet in color, sessile base, approximately two centimeters, located in the left labial commissure, was identified. Diascopy was performed to confirm the origin of the alteration, which revealed that it was a vascular le sion. As the patient was elderly, hypertensive, with a history of stroke, conservative treatment was chosen, with sclerotherapy with 5% mon oethanolamine oleate in a single session. On return after seven days, partial regression of the lesion was observed and, after 30 days, the region was completely healed, with no traces of the alteration. Mon oethanolamine oleate causes a sterile, acute, dose-dependent inflam matory reaction in the vascular endothelium and extravascular tissues that results in fibrosis and obliteration of blood vessels, inducing re gression of the lesions. Conclusion: Based on the case presented and on the literature records, it is possible to affirm that sclerotherapy is a minimally invasive, effective, low-cost therapeutic alternative with a favorable aesthetic result in the treatment of oral vascular lesions... (AU)

Objetivo: presentar un caso de lesión vascular en un paciente de edad avanzada, tratado mediante la técnica de escleroterapia. Reporte de caso: paciente masculino, 67 años, víctima de un derrame cerebral, buscó atención odontológica por raíces dentarias residuales. Durante el examen físico se identificó una lesión exofítica, de color violeta, de base sésil, de aproximadamente dos centímetros, ubicada en la comisura labial izquierda. Se realizó diascopia para confirmar el origen de la alteración, que reveló que se trataba de una lesión vascular. Como el paciente era anciano, hipertenso, con antecedentes de ictus, se optó por tratamiento conservador, con escleroterapia con oleato de monoetanolamina al 5% en una sola sesión. Al regreso a los siete días se observó una regresión parcial de la lesión y, a los 30 días, la región estaba completamente curada, sin rastros de la alteración. El oleato de monoetanolamina provoca una reacción inflamatoria estéril, aguda y dependiente de la dosis en el endotelio vascular y los tejidos extravasculares que produce fibrosis y obliteración de los vasos sanguíneos, lo que induce la regresión de las lesiones. Conclusión: Con base en el caso presentado y en los registros de la literatura, es posible afirmar que la escleroterapia es una alternativa terapéutica mínimamente invasiva, efectiva, de bajo costo y con resultado estético favorable en el tratamiento de las lesiones vasculares orales... (AU)

Acute high-intensity interval exercise versus moderate-intensity continuous exercise in heated water-based on hemodynamic, cardiac autonomic, and vascular responses in older individuals with hypertension.

OBJECTIVES: This crossover study design aimed to assess hemodynamic, cardiac autonomic, and vascular responses to high-intensity interval (HIIE) vs moderate-intensity continuous exercise (MICE) in older individuals with hypertension. METHODS: Twenty (67 ± 7 y) older individuals with hypertension were randomly assigned to perform HIIE, MICE, or control (CON) sessions in the heated swimming pool (30-32°C). Blood pressure (BP), arterial stiffness, endothelial reactivity, and heart rate variability (HRV) were measured pre, post, and 45 min (recovery) after each intervention followed by 24-h ambulatory BP and HRV. RESULTS: One single aerobic exercise session was not effective to provoke post-exercise hypotension and vascular improvements. HIIE was superior to MICE and CON to increasing parasympathetic modulation at post and recovery. Exercise sessions showed to disturb the autonomic system at nighttime compared to CON. CONCLUSIONS: These results may have important implications in water-based therapy and the elderly with hypertension.

Aging whole blood transcriptome reveals candidate genes for SARS-CoV-2-related vascular and immune alterations.

The risk of severe COVID-19 increases with age as older patients are at highest risk. Thus, there is an urgent need to identify how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with blood components during aging. We investigated the whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins interacting with viral proteins during aging. From 22 DEGs in aged blood, FASLG, CTSW, CTSE, VCAM1, and BAG3 were associated with immune response, inflammation, cell component and adhesion, and platelet activation/aggregation. Males and females older than 50 years old overexpress FASLG, possibly inducing a hyperinflammatory cascade. The expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 also increased throughout aging in both genders. By exploring single-cell RNA-sequencing data from peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed in natural killer cells and CD8 + T lymphocytes, whereas BAG3 was expressed mainly in CD4 + T cells, naive T cells, and CD14 + monocytes. In addition, T cell exhaustion was associated with increased expression of CCL4L2 and DUSP4 over blood aging. LAG3, PDCD1, TIGIT, VCAM1, HLA-DRA, and TOX also increased in individuals aged 60-69 years old; conversely, the RGS2 gene decreased with aging. We further identified a distinct gene expression profile associated with type I interferon signaling following blood aging. These results revealed changes in blood molecules potentially related to SARS-CoV-2 infection throughout aging, emphasizing them as therapeutic candidates for aggressive clinical manifestation of COVID-19. KEY MESSAGES: • Prediction of host-viral interactions in the whole blood transcriptome during aging. • Expression levels of FASLG, CTSW, CTSE, VCAM1, and BAG3 increase in aged blood. • Blood interactome reveals targets involved with immune response, inflammation, and blood clots. • SARS-CoV-2-infected patients with high viral load showed FASLG overexpression. • Gene expression profile associated with T cell exhaustion and type I interferon signaling were affected with blood aging.

Fisiología respiratoria: circulación pulmonar / Respiratory physiology: pulmonary circulation

El pulmón recibe sangre desde la circulación bronquial y pulmonar. La circulación pulmonar presenta importantes diferencias con la sistémica, sus vasos sanguíneos poseen características únicas que le permiten cumplir sus diferentes funciones, siendo la más importante el intercambio gaseoso. Existen múltiples factores, activos y pasivos, que están involucrados en la regulación de la resistencia vascular y flujo sanguíneo pulmonar.

The lung receives blood from the bronchial and the pulmonary circulation. The pulmonary circulation presents important differences with the systemic circulation, its blood vessels have unique characteristics that allow them to fulfill their different functions, the most important being gas exchange. There are multiple factors, active and passive, that are involved in the regulation of vascular resistance and pulmonary blood flow.

Avaliação ultrassonográfica de variações anatômicas entre vasos femorais realizada por estudantes de medicina / Ultrasonographic evaluation of anatomical variations in femoral vessels done by medical students

Introdução: A punção venosa central é um procedimento médico tradicionalmente realizado seguindo os marcadores anatômicos como referência para atingir o vaso, às cegas. No entanto, nem sempre o sucesso nessa técnica é alcançado, fato que se deve principalmente às variações anatômicas. A ultrassonografia point of care (US-POC) é utilizada para auxiliar a cateterização central por visualização direta do vaso, aumentando a segurança do procedimento. Objetivo: Avaliar a prevalência das variações anatômicas de vasos femorais através da utilização da US-POC por estudantes de medicina submetidos a curto período de treinamento. Material e Métodos: Cinco estudantes de medicina, sem experiência prévia em US-POC, foram submetidos a oito horas de treinamento teórico-prático. Foram avaliados os vasos femorais de cem voluntários. Resultados: A veia femoral direita foi encontrada mais frequentemente na posição medial (43%) em relação à artéria femoral direita. À esquerda, a posição posteromedial foi a mais observada (45%).Conclusão: A técnica tradicional de punção de acesso central se baseia em marcadores anatômicos e não leva em consideração as variações anatômicas existentes. Um treinamento de curto período para uso da US-POC é capaz de capacitar o profissional para reconhecer o posicionamento real dos vasos e evitar punções inadvertidas.

Introduction: Central vein puncture is a medical procedure traditionally done following anatomical landmarks as a reference to successfully achieving the vessel. However, this traditional technique is commonly unsuccessful due to anatomical variations that may be found. Point of care ultrasonography (POC-US) is used to assist central catheterization by directly visualizing the vessel, increasing procedure security and minimizing risks. Objective: Evaluate anatomical variations prevalence in femoral vessels, utilizing POC-US, done by medical students submitted to a short period of time training in ultrasonography. Material and Methods: Five medical students, without previous experience on the use of ultrasonography, were submitted to an eight-hour theorical practical training in POC-US. The students evaluated one hundred femoral vessels of volunteers. Results: The right limb femoral vein was found more frequently in the medial position (43%) in comparison to the right limb femoral artery. On the left limb, the posteromedial position was the most found (45%). Conclusion: The insertion of a central catheter following the traditional technique is based on anatomical landmarks, and does not take into account existing anatomical variations. With a short period of training, POC-US is capable of qualifying professionals to acknowledge the real location of the vessel and avoid inadvertent punctures and complications.

Anatomia e histologia do esôfago e vasos sanguíneos em Cães ­ Revisão de literatura / Anatomy and histology of the esophagus and blood vessels in dogs ­ Literature review

O sistema digestório é composto por órgãos de morfologia tubular, e glândulas associadas; tendo como principal função o processamento de alimentos e a absorção de nutrientes dos mesmos. Há um padrão estrutural comum entre órgãos tubulares deste sistema, o conhecimento desse padrão, facilita a compreensão das particularidades de cada órgão. Já os vasos sanguíneos são caracterizados e definidos por sua posição dentro do circuito vascular, pela estrutura individual, e mecanismos de controle da função vascular. Dessa forma, o objetivo do presente trabalho é aprofundar conhecimentos a respeito de anatomia e histologia do esôfago e vasos sanguíneos em cães.(AU)

The digestive system is composed of tubular morphology organs and associated glands; with the main function of food processing and nutrient absorption. There is a common structural pattern among tubular organs of this system, knowledge of this pattern facilitates the understanding of the particularities of each organ. Blood vessels are characterized and defined by their position within the vascular circuit, their individual structure, and the mechanisms that control vascular function. Thus, the objective of the present work is to deepen knowledge about the anatomy and histology of the esophagus and blood vessels.(AU)

Métodos ultrassonográficos na avaliação das afecções prostáticas em cães ­ revisão de literatura / Ultrasonographic methods in the evaluation of prostatic disorders in dogs ­ paper review

O objetivo desta revisão foi descrever as principais técnicas de avaliação e achados ultrassonográficos da próstata canina. A ultrassonografia é o método de escolha para avaliação da glândula prostática, sendo imprescindível como auxílio no diagnóstico na detecção de anormalidades, principalmente quando há suspeita da presença de tumores. Com inovação dos equipamentos, surgiram técnicas complementares à ultrassonografia modo Bidimensional (B), tais como Doppler, ultrassonografia contrastada e elastografia, que aumentam a acurácia diagnóstica. O Doppler fornece informações sobre arquitetura vascular e aspectos hemodinâmicos dos vasos sanguíneos. A ultrassonografia contrastada permite determinar parâmetros relacionados à perfusão sanguínea das estruturas pelos agentes de contraste (ex.: microbolhas), definindo, portanto, padrões de alta e baixa intensidade da arquitetura vascular. A elastografia proporciona a avaliação da rigidez tecidual tanto de forma qualitativa, por meio de elastogramas, quanto quantitativa, por meio das velocidades de cisalhamento. Espera-se que esta revisão possa contribuir com informações relevantes aos leitores e veterinários da área de ultrassonografia e reprodução animal.(AU)

The purpose of this review was to describe the main assessment techniques and ultrasound findings of the canine prostate. Ultrasonography is the method of choice for assessing the prostate gland, being essential as an aid in the diagnosis in the detection of abnormalities, especially when the presence of tumors is suspected. With the innovation of the equipment, complementary techniques to B-mode ultrasonography have emerged, such as Doppler, contrasted ultrasound and elastography, which increase the diagnostic accuracy. Doppler provides information on vascular architecture and hemodynamic aspects of blood vessels. Contrast ultrasonography allows to determine parameters related to the blood perfusion of structures by contrast agents (eg, microbubbles), thus defining high and low intensity patterns of vascular architecture. ARFI elastography provides assessment of tissue stiffness both qualitatively, using elastograms, and quantitative, using shear speeds. It is hoped that this review can contribute with relevant information to readers and veterinarians in the area of asound and animal reproduction.(AU)

Nanobubbles: A Novel Targeted Drug Delivery System

Abstract Nanobubbles are nanometer size bubbles having different constituents of varying physicochemical characteristic for the inner core and outer shell. Nanobubbles are mainly fabricated to improve the stability, bioavailability and improve the biodistribution of the delivered drug to the specific targeted site. Their small sizes bubbles allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Nanobubbles are developing as important contrast agents for imaging and carriers for drug delivery at targeted region. Sonication is the primary method for preparation of nanobubbles followed by thin-layer evaporation, high shear emulsification, mechanical agitation and coacervation or coalescence. With exposure to ultrasound/extracorporeal shock waves, the drug is liberated from the nanobubbles into the target cells. This review paper is an effort to reveal the different formulation development techniques briefly and varying shell and core content for developing nanobubbles.

Decreased body-fat accumulation and increased vasorelaxation to glyceryl trinitrate in middle-aged male rats following six-weeks consumption of coconut milk protein

Abstract We investigated whether coconut milk protein (CMP) contributes to the beneficial effects of coconut milk consumption on cardiovascular health markers previously found in middle-aged rats. CMP was isolated and precipitated from dried fresh coconut milk, then gavaged (1 g/kg) to middle-aged male rats for six weeks; control rats received distilled water. Compared to controls, CMP caused decreased body fat and lipid accumulation in liver cells and the platelet count. CMP did not affect basal blood pressure or heart rate in anesthetized rats. Vascular responsiveness to phenylephrine, DL-propargylglycine (PAG), acetylcholine or sodium nitroprusside was unaffected, but vasorelaxation to glyceryl trinitrate (GTN) increased. Effects of ODQ on vasorelaxation to GTN were similar in both groups. Expression of blood vessel eNOS, CSE and sGC was normal. The cyclic guanosine monophosphate (cGMP) level of CMP-treated rats was normal but addition of GTN increased cGMP and NO concentration more in CMP-treated rats than in controls, an effect unaltered by addition of diadzin. Taken together, CMP appears partially responsible for the improvement in cardiovascular health markers caused by coconut milk in middle-aged male rats

Granulomatose de Wegener: reabilitação oral com prótese bucomaxilofacial / Wegener's granulomatosis: oral rehabilitation with maxillofacial prosthesis / Granulomatosis de Wegener: rehabilitación oral con prótesis bucomaxilofacial

Introdução: A granulomatose de Wegener é uma doença autoimune rara que ocorre através de mediadores imunológicos. Sua etiologia permanece desconhecida. No entanto, sabe-se que é caracterizada principalmente pela inflamação dos vasos sanguíneos que acometem preferencialmente as vias aéreas superiores, inferiores e os rins. A doença apresenta altas taxas de morbidade e mortalidade quando não tratada, seu principal tratamento é através do uso de corticoides e imunossupressores. Objetivo: realizar um relato de caso de Granulomatose de Wegener tratando a comunicação orosinusal através de prótese bucomaxilofacial e uma discussão baseada na literatura recente. Relato de caso: paciente do gênero masculino, 40 anos de idade, leucoderma, encaminhado ao serviço de Bucomaxilofacial do Hospital Universitário da Universidade Federal de Santa Catarina (HU-UFSC) queixando-se de comunicação oronasal em região de palato. Foi tratado com prótese BMF obturadora, o que devolveu ao paciente a capacidade de fonação, deglutição e convívio social. Conclusão: o tratamento com a prótese BMF reestabelece o velamento velofaríngeo, corrige hipernasalidade, melhora a deglutição e dá conforto psicológico ao paciente com estabilidade protética funcional... (AU)

Introduction: Wegeners' Granulomatulosis is a rare autoimmune disease that acts through immunologic mediators. It's etymology remains unknown. However, it is known that it's mainly characterized by the inflammation of blood vessels that affect, by preference, upper and lower airways, as well as kidneys. The disease presents high rates of morbidity and mortality when not treated, and it's main treatments are corticoids and immunosuppressants. Objective: Perform a Wegener's Granulomatulosis case report treating orosinusal communication through the use of a bucomaxilofacial prosthesis and a discussion based on current literature. Case report: Male patient, 40 years of age, leucoderma, brought to the Bucomaxilofacial department of Federal University of Santa Catarina (HU UFSC) with complaints regarding oronasal communication in the palate region. The patient was treated with a BMF prosthetics, which has allowed the patient to resume normal social activities, as well as returning phonation and deglutition. Conclusion: Treatment with a BMF prosthetics reestablishes velopharyngeal veiling, assists in the correction of nasal voice, improves deglutition and offers the patient psychological comfort with functional prosthetic stability... (AU)

Introducción: la granulomatosis de Wegener es una enfermedad autoinmune rara que se presenta a través de mediadores inmunológicos. Su etiologia permanece desconocida. Sin embargo, se sabe que se caracteriza principalmente por la inflamación de los vasos sanguíneos que afectan preferentemente las vías respiratorias superiores e inferiores y los riñones. La enfermedad tiene altas tasas de morbilidad y mortalidad cuando no se trata, su principal tratamiento es mediante el uso de corticosteroides e inmunosupresores. Objetivo: realizar un reporte de caso de Granulomatosis de Wegener en el tratamiento de la comunicación orosinusal mediante prótesis maxilofacial y una discusión basada en la literatura reciente. Caso clínico: paciente de sexo masculino, 40 años, leucoderma, remitido al Servicio Maxilofacial del Hospital Universitario de la Universidad Federal de Santa Catarina (HU-UFSC) por comunicación oronasal en región paladar. Fue tratado con una prótesis obturatriz de BMF, que le devolvió al paciente la capacidad de hablar, tragar y socializar. Conclusión: el tratamiento con la prótesis BMF restablece el velo velofaríngeo, corrige la hipernasalidad, mejora la deglución y proporciona confort psicológico al paciente con estabilidad protésica funcional... (AU)