The vascular footprint in cardiac homeostasis and hypertensive heart disease-A link between apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase.

Recent studies have suggested a connection between disturbances of the apelin system and various cardiac pathologies, including hypertension, heart failure, and atherosclerosis. Vascular endothelial growth factor is crucial for cardiac homeostasis as a critical molecule in cardiac angiogenesis. Neuronal nitric oxide synthase is an essential enzyme producing nitric oxide, a key regulator of vascular tone. The present study aims to shed light upon the complex interactions between these three vital signaling molecules and examine their changes with the progression of hypertensive heart disease. We used two groups of spontaneously hypertensive rats and age-matched Wistar rats as controls. The expression of the apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase were assessed immunohistochemically. We used capillary density and cross-sectional area of the cardiomyocytes as quantitative parameters of cardiac hypertrophy. Immunoreactivity of the molecules was more potent in both ventricles of spontaneously hypertensive rats compared with age-matched controls. However, capillary density was lower in both ventricles of the two age groups of spontaneously hypertensive rats compared with controls, and the difference was statistically significant. In addition, the cross-sectional area of the cardiomyocytes was higher in both ventricles of the two age groups of spontaneously hypertensive rats compared with controls, and the difference was statistically significant. Our study suggests a potential link between the apelin receptor, vascular endothelial growth factor, and neuronal nitric oxide synthase in cardiac homeostasis and the hypertensive myocardium. Nevertheless, further research is required to better comprehend these interactions and their potential therapeutic implications.

Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Variant origin of the right coronary artery from the left main coronary artery together with aortic valve stenosis: report of a rare case / Origen variante de la arteria coronaria derecha a partir de la arteria coronaria izquierda junto con estenosis de la valva aórtica: reporte de un caso raro

SUMMARY: Variations in the origin of the right coronary artery have an incidence between 0.09 % and 0.92 %. Herein, we report a rare case of a coronary artery anomaly in which the right coronary artery originates from the left main coronary artery. This variant was found during routine coronarography, combined with an artificial aortic valve. Despite their rare occurrence, some variations in the origins of the coronary arteries can be life threatening and are associated with a higher risk of sudden cardiac death. They can also pose serious technical challenges and predispose to complications during coronary angiographic procedures. Thus, knowledge of such anomalies is paramount for managing the patients correctly.

Las variaciones en el origen de la arteria coronaria derecha tienen una incidencia entre el 0,09 % y el 0,92 %. En este documento, informamos un caso raro de una anomalía de la arteria coronaria en la que la arteria coronaria derecha se originaba en la arteria coronaria izquierda. Esta variante se encontró durante una coronariografía de rutina, combinada con una válvula aórtica artificial. A pesar de su rara aparición, algunas variaciones en los orígenes de las arterias coronarias pueden poner en peligro la vida y se asocian con un mayor riesgo de muerte súbita cardíaca. También pueden plantear serios desafíos técnicos y predisponer a complicaciones durante los procedimientos angiográficos coronarios. Por tanto, el conocimiento de dichas anomalías es fundamental para el manejo correcto de los pacientes.

Patella cubiti - a continuing etiological mystery / Patella cubiti: un misterio etiológico continuo

SUMMARY: A sesamoid bone in the elbow joint is a rare anatomical variation described as a Patella cubiti. Although this variation has been known for centuries its exact etiology is still unclear. Congenital, developmental, and traumatic hypotheses have been proposed. It seldom causes clinical manifestations than elbow stiffness or hypomobility. Herein, we present a case of a 31-year-old patient admitted to our department with complaints of swelling and erythema in the right elbow. An X-ray image revealed a triangular accessory bone with rounded edges, which was diagnosed as a Patella cubiti in combination with olecranon bursitis. Knowledge of this rare elbow abnormality is paramount for orthopedic surgeons and roentgenologists in their daily medical practice.

Un hueso sesamoideo en la articulación del codo es una rara variación anatómica descrita como Patella cubiti. Aunque esta variación se conoce desde hace siglos, su etiología exacta aún no está clara. Se han propuesto hipótesis congénitas, de desarrollo y traumáticas. Rara vez causa manifestaciones clínicas que no sean rigidez o hipomovilidad del codo. Presentamos el caso de un paciente de 31 años que ingresó en nuestro servicio por presentar tumefacción y eritema en el codo derecho. Una imagen de rayos X reveló un hueso accesorio triangular con márgenes redondeados, que se diagnosticó como una Patella cubiti en combinación con bursitis del olécranon. El conocimiento de esta rara anomalía del codo es fundamental para los cirujanos ortopédicos y los médicos radiólogos en su práctica médica diaria.

Depletion of vascular adaptive mechanisms in hypertension-induced injury of the heart and kidney.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a signalling protein of critical importance for angiogenesis. In an effort to better understand its significance in hypertension-induced injury of the heart and kidney we aimed at studying the changes in its expression in an experimental model and correlated it with capillary density in the myocardium and the renal parenchyma. METHODS: We used two age groups of spontaneously hypertensive rats (6- and 12-month-old), indicative of early and advanced hypertension. VEGF expression was assessed and a semi-quantitative analysis of its immunoreactivity was conducted. Changes in capillary density in the myocardium and kidney were assessed for statistical significance and correlations with VEGF expression were established. RESULTS: We reported stronger VEGF expression in animals with early compared to advanced hypertension in all examined structures. Capillary density decreased significantly at age 12 months compared to 6 months and was significant in all examined structures. A positive correlation was established between capillary density and the expression of VEGF. CONCLUSION: These findings underscore the key significance of VEGF for compensatory angiogenesis and suggest that a statistically significant depletion of these vascular adaptive mechanisms is a major aspect in the cascade of hypertension-induced injury of the heart and kidney (Tab. 3, Fig. 26, Ref. 47).

Personalized Approach in Treatment of Neovascular Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a progressive, degenerative disease of the central retina. AMD is subdivided into "dry" (atrophic), "wet" (exudative), and neovascular (nAMD) forms. In recent years, the concepts about nAMD changed with the development of optical coherence tomography-angiography (OCT-A) and intravitreal anti-VEGF treatment. The aim of this study was to define the morphologic type of the neovascular membrane (NVM) before treatment with OCT-A and to register vascular remodeling after treatment with anti-VEGF. We also analyzed the relationship between NVM and visual acuity. METHODS: The study was retrospective and included 119 patients with newly diagnosed, treatment-naïve nAMD. All the patients underwent full ophthalmic examination and also fluoresceine angiography and optical coherence tomography-angiography (OCT-A). RESULTS: Based on the collected data, we found repetitive regularities. CONCLUSION: The analysis of our results could be used as prognostic markers for the evolution of the disease and as a basis for new treatment strategies, depending on the naïve NVM morphologic type.

Mast cells and basic fibroblast growth factor in physiological aging of rat heart and kidney.

Age-related morphological and physiological changes occur in cells, tissues and organs with high metabolic or mitotic activity; these changes decrease their regenerative capacity. One such change is interstitial fibrosis. Mast cells contain basic fibroblast growth factor and have been related to pro-fibrotic activity. We investigated the role of mast cells in physiological aging of the heart and kidney. We analyzed changes in mast cell number and compared the left and right heart ventricles and kidneys of 6- and 12-month-old Wistar rats. We also evaluated the immunohistochemical expression of basic fibroblast growth factor. Finally, we analyzed changes in the extent of interstitial fibrosis and in the glomerular sclerosis index as nonspecific markers of aging and correlated these parameters with of mast cells. Mast cells were visualized by toluidine blue staining and specific immunohistochemical expression of tryptase. The expression of basic fibroblast growth factor was assessed semiquantitatively. The extent of interstitial fibrosis was investigated using Mallory's trichrome staining. Glomerular sclerosis was evaluated using periodic acid-Schiff staining. We found that the number of mast cells increased significantly in the older rats. We also found that the number of mast cells was greatest in the left ventricle followed by the right ventricle, then the kidney. The immunoreactivity of basic fibroblast growth factor also increased in older animals. Correlations between the number of mast cells and immunoreactivity of basic fibroblast growth factor, extent of interstitial fibrosis and glomerular sclerosis index demonstrated the association between mast cells and age-related tissue remodeling of the heart and kidney.

A comparative immunohistochemical and quantitative study of the epiligament of the medial collateral and anterior cruciate ligament in rat knee / Estudio inmunohistoquímico y cuantitativo del epiligamento del ligamento colateral medial y cruzado anterior en rodilla de rata

SUMMARY: The aim of the present study was to evaluate the importance of the epiligament for the difference in the healing potential of the knee anterior cruciate and medial collateral ligament. To do so, we compared the structure of the anterior cruciate and the medial collateral ligament and evaluated the differences in the expression of collagen types I, III and V in a rat knee. We have also conducted a comparative quantitative analysis of the number of cells per mm2 in the two ligaments. Tissue samples were obtained from the anterior cruciate and medial collateral ligament of 10 knee joints taken from five 8-month-old Wistar rats. We used standard hematoxylin and eosin staining, in addition to immunohistochemical staining with monoclonal antibodies against collagen types I, III and V. A semi-quantitative analysis of the expression was made through ImageJ, while Student's T-test was used for the statistical analysis. Our results showed higher expression of all collagen types in the epiligament, compared to the ligament proper and difference in the expression between the medial collateral and the anterior cruciate ligament in favor of the first. We also reported a statistically significant difference in the number of cells per mm2 between the two ligaments and their epiligaments. Our findings show a higher number of cells and a stronger expression of certain collagen types in the epiligament of the medial collateral compared to the anterior cruciate ligament, which may be related to the difference in their healing potential.

RESUMEN: El objetivo del presente estudio fue evaluar la importancia del epiligamento para la diferencia en el potencial de curación del ligamento cruzado anterior y colateral medial de la rodilla. Comparamos la estructura del ligamento cruzado anterior y el ligamento colateral medial y evaluamos las diferencias en la expresión de los tipos de colágeno I, III y V en una rodilla de rata. También se realizó un análisis cuantitativo comparativo del número de células por mm2 en los dos ligamentos. Se obtuvieron muestras de tejido del ligamento cruzado anterior y colateral medial de 10 articulaciones de rodilla tomadas de cinco ratas Wistar de 8 meses de edad. Utilizamos tinción estándar con hematoxilina y eosina, además de tinción inmunohistoquímica con anticuerpos monoclonales contra colágeno tipo I, III y V. Se realizó un análisis semicuantitativo de la expresión mediante ImageJ, mientras que para el análisis estadístico se utilizó la prueba T de Student. Nuestros resultados mostraron una mayor expresión de todos los tipos de colágeno en el epiligamento, en comparación con el ligamento y una diferencia en la expresión entre el ligamento colateral medial y el ligamento cruzado anterior. También informamos una diferencia estadísticamente significativa en el número de células por mm2 entre los dos ligamentos y sus epiligamentos. Nuestros hallazgos muestran un mayor número de células y una expresión mayor de ciertos tipos de colágeno en el epiligamento colateral medial en comparación con el ligamento cruzado anterior, lo que puede estar relacionado con la diferencia en su potencial de curación.

Cytoarchitecture of the dorsal claustrum of the cat: a quantitative Golgi study.

The claustrum is a subcortical nucleus, found in the telencephalon of all placental mammals. Earlier Golgi studies have mostly focused on a qualitative description of the types of neurons. The aim of the present study was to describe the types of neurons found in the dorsal claustrum of the cat using the Golgi impregnation method and to perform a quantitative analysis of the following morphometric parameters: number of terminals (ends), total dendritic length, dendritic complexity, spine density (in spiny projection neurons), varicosity density (in aspiny interneurons). We used specimens from 5 healthy male cats stained according to the Golgi-Cox method. The dendritic trees of the studied neurons were then reconstructed through the Neurolucida software. Values of the studied quantitative parameters were obtained automatically and tested for statistically significant differences. Five types of spiny neurons were observed-large, medium-sized and small multipolar, bipolar and pyramidal-like. In addition, we described three types of aspiny neurons. The quantitative values and the statistical analysis were presented with tables and diagrams. In conclusion, we have presented a detailed analysis of the cytoarchitecture of the DC of the cat and have reported the first quantitative data on a number of morphometric parameters.

Ultrastructure of the dorsal claustrum in cat. II. Synaptic organization.

The claustrum is a bilateral subcortical nucleus situated between the insular cortex and the striatum in the brain of all mammals. It consists of two embryologically distinct subdivisions - dorsal and ventral claustrum. The claustrum has high connectivity with various areas of the cortex, subcortical and allocortical structures. It has long been suggested that the various claustral connections have different types of synaptic contacts at the claustral neurons. However, to the best of our knowledge, the literature data on the ultrastructural organization of the different types of synaptic contacts in the dorsal claustrum are very few. Therefore, the aim of our study was to observe and describe the synaptic organization of the dorsal claustrum in the cat. We used a total of 10 adult male cats and conducted an ultrastructural study under a transmission electron microscope as per established protocol. We described a multitude of dendritic spines, which were subdivided into two types - with and without foot processes. Based on the size and shape of the terminal boutons, the quantity and distribution of vesicles and the characteristic features of the active synaptic zone, we described six types of synaptic boutons, most of which formed asymmetrical synaptic contacts. Furthermore, we reported the presence of axo-dendritic, axo-somatic, dendro-dendritic and axo-axonal synapses. The former two likely represent the morphological substrate of the corticoclaustral pathway, while the remaining two types have the ultrastructural features of inhibitory synapses, likely forming a local inhibitory circuit in the claustrum. In conclusion, the present study shares new information about the neuropil of the claustrum and proposes a systematic classification of the types of synaptic boutons and contacts observed in the dorsal claustrum of the cat, thus supporting its key and complex role as a structure integrating various information within the brain.

Correction: Epiligament Tissue of the Medial Collateral Ligament in Rat Knee Joint: Ultrastructural Study.

[This corrects the article DOI: 10.7759/cureus.3812.].

Epiligament Tissue of the Medial Collateral Ligament in Rat Knee Joint: Ultrastructural Study.

Introduction Recent studies stressed the importance of the epiligament in ligament nutrition and healing. While ligaments of the knee joint have been the subject of extensive research, the epiligament of the medial collateral ligament has received only limited attention. The aim of our study was to present the ultrastructural morphological features of the epiligament of the medial collateral ligament in a rat knee joint. Materials and methods For the present study, we used eight eight-month-old male Wistar rats. A transmission electron microscopic study of the epiligament was conducted according to standard protocol. Results In the epiligament, we described the presence of fibroblasts with the typical features of protein-synthesizing cells, as well as fibrocytes and adipocytes. We noted an abundance of blood vessels and nerve elements. Collagen fibers were organized in multidirectional bundles. Conclusions Our findings confirm that the cells and structures of the epiligament play an important role in the nutrition and healing of the medial collateral ligament.