Vitrectomy-Assisted Excision in the Treatment of Juxtapapillary Retinal Capillary Hemangioma.

Juxtapapillary retinal capillary hemangiomas are sight-threatening hamartomas located on or adjacent to the optic nerve. Nonsurgical approaches including laser photocoagulation and cryotherapy have been shown to be effective to reduce exudation in peripheral hemangiomas. However, in juxtapapillary hemangiomas, the functional outcomes are limited due to associated potential damage of the retinal nerve fiber layer. We present an 18-year-old female patient with von Hippel-Lindau (VHL) disease who presented with a juxtapapillary retinal capillary hemangioma associated with a tractional epiretinal membrane (ERM) and secondary macular hole. After vitrectomy-assisted excision of the lesion and inner limiting membrane (ILM) peeling around the macular hole, visual acuity and macular anatomy were recovered at 10 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina 2022;53:570-573.].

Lipogranuloma Esclerosante Escrotal Primario. Reporte de caso y revisión de la literatura / Primary Scrotal Sclerosing Lipogranuloma. Case report and literature review

RESUMEN El lipogranuloma esclerosante es una condición extraña y benigna que puede afectar cualquier órgano, especialmente los genitales externos masculinos. Se suele presentar como masas subcutáneas en escroto, periné y pene. Aunque la mayoría de los casos son secundarios a aplicación de cuerpos extraños como parafina, vaselina o silicona con propósitos estéticos para aumentar el tamaño del pene, también puede deberse a degeneración lipídica endógena, secundaria a trauma, infecciones o reacciones alérgicas. No existe consenso en cuanto a su manejo ni datos sobre su prevalencia al ser una entidad poco reportada; se ha descrito el manejo con ciclos cortos de corticoides sistémicos, y cirugía en los casos recidivantes. El objetivo de este trabajo es reportar el caso de un paciente que acudió con induración y eritema en pene y escroto, quien negaba la aplicación de sustancias exógenas y que fue llevado a biopsia de la lesión, con diagnóstico de lipogranuloma esclerosante. MÉD.UIS.2021;34(2): 97-102.

ABSTRACT Sclerosing lipogranuloma is a noncommon and benign disease that could affect any system in the body, especially the male external genitalia. It is usually presented as a subcutaneous mass in scrotum, perineum and penis. Although, most cases are secondary to the injection of foreign bodies such as paraffin, petrolatum or silicone for cosmetic purposes to increase penis size, it could also be due to endogenous lipid degeneration, secondary to trauma, infections or allergic reactions. There is no unanimity regarding its management or data on its prevalence as it is a poorly reported entity. Management with short cycles of systemic corticosteroids and surgery in relapsing cases have been described. The purpose of this article is to present a case of a patient with induration and erythema in penis and scrotum, who denied the application of exogenous substances and has a reported biopsy of the lesion with diagnosis of sclerosing lipogranuloma. MÉD.UIS.2021;34(2): 97-102.

Manifestaciones cutáneas de la infección por citomegalovirus en un paciente con compromiso inmunitario / Cutaneous manifestations of cytomegalovirus infection in an immunocompromised patient

El citomegalovirus es un patógeno oportunista que frecuentemente afecta pacientes con compromiso inmunitario. Diferentes órganos pueden resultar afectados, y las lesiones en piel son raras e inespecíficas. Se presenta el caso de un hombre de 70 años con diagnóstico de leucemia linfocítica crónica e infección por citomegalovirus con manifestaciones cutáneas.

Comparison of active vitamin D compounds and a calcimimetic in mineral homeostasis.

The differential effects between cinacalcet and active vitamin D compounds on parathyroid function, mineral metabolism, and skeletal function are incompletely understood. Here, we studied cinacalcet and active vitamin D compounds in mice expressing the null mutation for Cyp27b1, which encodes 25-hydroxyvitamin D-1α-hydroxylase, thereby lacking endogenous 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Vehicle-treated mice given high dietary calcium had hypocalcemia, hypophosphatemia, and marked secondary hyperparathyroidism. Doxercalciferol and 1,25(OH)(2)D(3) each normalized these parameters and corrected both the abnormal growth plate architecture and the diminished longitudinal bone growth observed in these mice. In contrast, cinacalcet suppressed serum parathyroid hormone (PTH) cyclically and did not correct the skeletal abnormalities and hypocalcemia persisted. Vehicle-treated mice given a "rescue diet" (high calcium and phosphorus, 20% lactose) had normal serum calcium and PTH levels; cinacalcet induced transient hypocalcemia and mild hypercalciuria. The active vitamin D compounds and cinacalcet normalized the increased osteoblast activity observed in mice with secondary hyperparathyroidism; cinacalcet, however, increased the number and activity of osteoclasts. In conclusion, cinacalcet reduces PTH in a cyclical manner, does not eliminate hypocalcemia, and does not correct abnormalities of the growth plate. Doxercalciferol and 1,25(OH)(2)D(3) reduce PTH in a sustained manner, normalize serum calcium, and improve skeletal abnormalities.

The calcium-sensing receptor and 25-hydroxyvitamin D-1alpha-hydroxylase interact to modulate skeletal growth and bone turnover.

We examined parathyroid and skeletal function in 3-month-old mice expressing the null mutation for 25-hydroxyvitamin D-1alpha-hydroxylase [1alpha(OH)ase(-/-)] and in mice expressing the null mutation for both the 1alpha(OH)ase and the calcium-sensing receptor [Casr(-/-)1alpha(OH)ase(-/-)] genes. On a normal diet, all mice were hypocalcemic, with markedly increased parathyroid hormone (PTH), increased trabecular bone volume, increased osteoblast activity, poorly mineralized bone, enlarged and distorted cartilaginous growth plates, and marked growth retardation, especially in the compound mutants. Osteoclast numbers were reduced in the Casr(-/-)1alpha(OH)ase(-/-) mice. On a high-lactose, high-calcium, high-phosphorus "rescue" diet, serum calcium and PTH were normal in the 1alpha(OH)ase(-/-) mice but increased in the Casr(-/-)1alpha(OH)ase(-/-) mice with reduced serum phosphorus. Growth plate architecture and mineralization were improved in both mutants, but linear growth of the double mutants remained abnormal. Mineralization of bone improved in all mice, but osteoblast activity and trabecular bone volume remained elevated in the Casr(-/-)1alpha(OH)ase(-/-) mice. These studies support a role for calcium-stimulated maturation of the cartilaginous growth plate and mineralization of the growth plate and bone and calcium-stimulated CaSR-mediated effects on bone resorption. PTH-mediated bone resorption may require calcium-stimulated CaSR-mediated enhancement of osteoclastic activity. (c) 2010 American Society for Bone and Mineral Research.

The presence of abdominal obesity is associated with changes in vascular function independently of other cardiovascular risk factors.

BACKGROUND: Because of the strong association between abdominal obesity (AO) and other cardiovascular risk factors, it has been difficult to determine which changes in vascular function are directly related to this condition. Our objective was to evaluate the changes in ex-vivo vascular reactivity, circulating levels of adipokines and inflammatory markers associated with the presence of AO in subjects who underwent coronary artery bypass graft (CABG) controlling by the presence of other cardiovascular risk factors. METHODS: Subjects scheduled for a CABG with (n=17) and without (n=17) AO (defined as a waist circumference > or =90 cm for male or > or =80 cm for female) whom were matched by several cardiovascular risk factors, were included in the study. Lipid profile and plasma levels of glucose, insulin, leptin, adiponectin and inflammatory markers were measured. Internal mammary artery segments were used for ex-vivo vascular reactivity experiments and morphometry. RESULTS: Leptin concentrations were higher and adiponectin concentrations were lower in subjects with AO. No differences were observed in other biochemical or clinical parameters between the groups. No correlation between waist circumference, HOMA index and inflammatory markers were observed. Endothelium-dependent relaxation to acetylcholine was lower, and contractile responses to angiotensin-II were higher in subjects with AO. These changes were not related to differences in vascular morphometry. CONCLUSION: In subjects with severe coronary disease, the presence of AO was associated with leptin/adiponectin imbalance, decreased endothelium-dependent relaxation and an enhanced response to angiotensin-II. These changes occurred independently of other cardiovascular risk factors including insulin resistance and levels of inflammatory markers.

Bone formation regulates circulating concentrations of fibroblast growth factor 23.

We examined the role of bone remodeling in the regulation of circulating concentrations of FGF23 using mouse models manifesting differing degrees of coupled and uncoupled bone turnover. Administration of the antiresorptive agent osteoprotegerin produced a profound reduction in bone resorption and formation in male and oophorectomized female mice, accompanied by an increase in serum levels of fibroblast growth factor 23 (FGF23) and a reduction in circulating 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. In contrast, exogenous PTH(1-34) administration increased bone turnover and reduced circulating FGF23. In 1,25(OH)(2)D-deficient, 25-hydroxyvitamin D 1alpha-hydroxylase null mice on a high-calcium diet, endogenous PTH was elevated, bone formation but not resorption was increased, and serum FGF23 was virtually undetectable; on a rescue diet, serum calcium was normalized, PTH levels were reduced, bone formation was reduced, and serum FGF23 levels increased. After PTH treatment of wild-type mice, gene expression of dentin matrix protein 1 (DMP1) in bone was increased, whereas gene expression of FGF23 was reduced. In vitro studies in the osteoblastic cell line UMR-106 showed that externally added DMP1 could inhibit FGF23 gene expression and production stimulated by 1,25(OH)(2)D(3). The results show that osteoblastic bone formation is a potent modulator of FGF23 production and release into the circulation, suggest that the biological consequences on mineral homeostasis of circulating FGF23 may also be dependent on the prevailing rate of bone turnover, and provide evidence that DMP1 may be a direct negative regulator of FGF23 production in osteoblastic cells.

Papel del óxido nítrico en la fisiología normal de la vía aérea y sus implicaciones en la fisiopatología de la hipertensión pulmonar / The role of nitric oxide (no) in the normal physiology of the airway and its implications on the pathophysiology of pulmonary hypertension / Papel do óxido nítrico na fisiología normal da via aérea e seus implicações na fisiopatología da hipertensão pulmonar

La hipertensión pulmonar es una patología de la microvasculatura pulmonar, caracterizada por un estado de vasoconstricción, proliferación endotelial, proliferación de músculo liso y trombosis. Se han implicado diversas moléculas en su etiología, demostrándose una producción elevada de agentes vasoconstrictores, mitogénicos, protrombóticos y mediadores proinflamatorios como tromboxano A2, endotelina (ET), el inhibidor del activador del plasminógeno y una menor producción de sustancias vasodilatadoras como la prostaciclina (PGI2) y el óxido nítrico (ON), que en condiciones fisiológicas actúa modulando el tono basal de los vasos pulmonares y también como mediador inflamatorio e inmunomodulador. La histopatología de las lesiones en la hipertensión pulmonar sugiere que el daño en el endotelio y los estímulos proliferativos son procesos fundamentales de su desarrollo, desencadenados por alteraciones en la producción o en la actividad del ON, ocasionados por acumulación de radicales libres que lleva a menor biodisponibilidad del ON. En el presente artículo se revisa el papel que juega el ON en la fisiología normal de la vía aérea y sus implicaciones en la fisiopatología de la hipertensión pulmonar...

Pulmonary hypertension is a disease of the pulmonary microvasculature characterized by vasoconstriction, smooth muscle and endothelial proliferation, and thrombosis. Many molecules have been implicated in the etiology, demonstrating an increased production of vasoconstrictor agents as well as mitogenic, prothrombotic and inflammatory mediators such as tromboxano A2, endothelin (ET), and the inhibitor of the plasminogen activator, together with a low production of vasodilator substances such as prostacyclin (PGI2) and nitric oxide (NO), which in physiological conditions, acts as a modulator of the basal tones of the pulmonary vessels, an inflammatory mediator, and an immunomodulator. The histopathology of the injuries in pulmonary hypertension, triggered by the alteration in the production or activity of NO, which is caused by an accumulation of free radicals that leads to lower bioavailability of NO, suggests that the damage in the endothelium and the proliferative stimulus are fundamental processes for their development. This article reviews the role played by NO in the normal physiology of the airway and its implications on the pathophysiology of pulmonary hypertension...

A hipertensão pulmonar é uma patologia da microvasculatura pulmonar, caracterizada por um estado de vasoconstrição, proliferação endotelial, proliferação de músculo liso e trombose. Implicaram-se diversas moléculas na sua etiologia, demonstrando-se uma produção elevada de agentes vasoconstrictores, miogênicos, pro trombóticos e mediadores proinflamatorios como tromboxano A2, endotelina (ET), o inhibidor do ativador do plasminógeno e uma menor produção de substâncias vasodilatadoras como a prostaciclina (PGI2) e o óxido nítrico (ON), que em condições fisiológicas atua modulando o tom basal dos copos pulmonares e também como mediador inflamatório e inmunomodulador. A histopatológica das lesões na hipertensão pulmonar sugere que o dano no endotélio e os estímulos proliferativos são processos fundamentais de seu desenvolvimento, desencadeados por alterações na produção ou na atividade do ON, ocasionados por acumulação de radicais livres que leva a menor biodisponibilidade do ON...

Papel del tejido perivascular en la regulación del tono vascular: repercusión en el uso de puentes aorto-coronarios para revascularización miocárdica / Role of perivascular tissue in vascular tone regulation: repercussion in the use of aortocoronary bypass for myocardial revascularization

Desde hace más de treinta años, la inserción quirúrgica de puentes aorto-coronarios autólogos de vena safena y de arteria mamaria, constituye el tratamiento de elección para pacientes con enfermedad coronaria severa. La vida útil de estos injertos ha demostrado ser mayor en los colgajos de tipo arterial, aunque su uso está limitado por la restringida disponibilidad de los mismos. Por esta razón, y a pesar de que tienen mayor riesgo de presentar oclusión, los injertos de vena safena son los que más se usan en estos procedimientos de reperfusión miocárdica. Aún no se han esclarecido del todo las razones por las cuales los injertos venosos se ocluyen luego de su inserción en los lechos arteriales; no obstante, se ha propuesto que podría deberse a diferentes factores como: trauma mecánico quirúrgico, aumento de la presión arterial y disminuido estrés de fricción.En 1996 se describió la técnica no-touch de preparación de los injertos venosos, en la cual se implantaron los puentes venosos en los lechos coronarios junto con el tejido peri-vascular que los circunda, y demostró mejorar la vida útil de este tipo de injertos. Recientemente se ha propuesto que el tejido adiposo peri-vascular podría desempeñar un papel en la regulación del tono vascular, e incluso se ha descrito la existencia de un factor relajante derivado del adipocito (ADRF), cuya naturaleza no se ha esclarecido completamente.El objetivo de este articulo es revisar los diferentes factores vinculados con la oclusión de los injertos aorto-coronarios, las posibles vías fisiopatológicas que configuran este fenómeno, las nuevas alternativas quirúrgicas utilizadas para la preparación de los injertos venosos y los avances en la descripción del ADRF y su papel en la regulación del tono vascular.

Since more than thirty years, surgical insertion of autologous aortocoronary bypasses from saphenous vein and mammary artery constitute the election treatment for patients with severe coronary disease. The lifespan of these grafts has shown to be longer with arterial tissue even though its use is limited by its restricted availability. This is why the saphenous vein bypasses, although having a greater risk of presenting occlusion, are the most used in these procedures of myocardial reperfusion. The reasons by which the venous grafts are occluded after its insertion in the arterial site are still not clear; nevertheless, it has been proposed that it could be due to different factors such as: surgical mechanical trauma, increment of arterial pressure and diminished friction stress. In 1996 the «no-touch¼ preparation technique of venous grafts was described, in which the venous bypasses were implanted in the coronary site along with the surrounding perivascular tissue and demonstrated to improve the lifespan of this type of grafts. Recently it has been proposed that the perivascular fat tissue could play a role in the vascular tone regulation and it has been even described the existence of an adipose cell derived relaxing factor (ADRF), whose nature has not been completely cleared yet. The objective of this article is to review the different factors related to the aortocoronary grafts’ occlusion, the possible physiopathologic channels that form this phenomenon, the new surgical alternatives used for vein grafts preparation and the advances in the description of ADRF and its role in vascular tone regulation.

Síndrome metabólico y preeclampsia: los aportes realizados por el Instituto de Investigaciones de la Fundación Cardiovascular de Colombia / Metabolic syndrome and pre-eclampsia: contributions realized by the research Institute of the Colombian Cardiovascular Foundation

Durante los últimos años, el Instituto de Investigaciones de la Fundación Cardiovascular de Colombia ha centrado sus proyectos en el estudio de las diferencias en los mecanismos etiofisiopatológicos de la hipertensión inducida por el embarazo y del síndrome metabólico en poblaciones de países desarrollados y en vía de desarrollo, así como en el peso específico de los factores de riesgo que determinan la presentación de estas enfermedades. Los resultados obtenidos de las investigaciones realizadas en la población, sugieren que los cambios de hábitos de vida ocasionados por la sociedad consumista, son el principal determinante del riesgo aumentado de preeclampsia y enfermedades cardiovasculares que al momento presenta la población colombiana.

The Research Institute of the Colombian Cardiovascular Foundation has centered its projects during the last years in the study of the differences in the etio-physiopathologic mechanisms of pregnancy induced hypertension and in the metabolic syndrome in populations of developed and underdeveloped countries, as well as in the value of the risk factors that determine the appearance of these diseases. The results obtained from the investigations realized in the population suggest that changes in life costumes due to a consumer society are the main determinant of the increased risk of pre-eclampsia and cardiovascular diseases that the Colombian population presents at this moment.

Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis.

We employed a genetic approach to determine whether deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D) and deficiency of the vitamin D receptor (VDR) produce the same alterations in skeletal and calcium homeostasis and whether calcium can subserve the skeletal functions of 1,25(OH)2D and the VDR. Mice with targeted deletion of the 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha(OH)ase-/-) gene, the VDR gene, and both genes were exposed to 1) a high calcium intake, which maintained fertility but left mice hypocalcemic; 2) this intake plus three times weekly injections of 1,25(OH)2D3, which normalized calcium in the 1alpha(OH)ase-/- mice only; or 3) a "rescue" diet, which normalized calcium in all mutants. These regimens induced different phenotypic changes, thereby disclosing selective modulation by calcium and the vitamin D system. Parathyroid gland size and the development of the cartilaginous growth plate were each regulated by calcium and by 1,25(OH)2D3 but independent of the VDR. Parathyroid hormone secretion and mineralization of bone reflected ambient calcium levels rather than the 1,25(OH)2D/VDR system. In contrast, increased calcium absorption and optimal osteoblastogenesis and osteoclastogenesis were modulated by the 1,25(OH)2D/VDR system. These studies indicate that the calcium ion and the 1,25(OH)2D/VDR system exert discrete effects on skeletal and calcium homeostasis, which may occur coordinately or independently.

Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T 1/2 mesenchymal cells.

We examined the effect of PTH-related peptide (PTHrP) on modulating adipogenesis and osteoblastogenesis in the pluripotent mesenchymal cell line C3H10T(1/2). These cells express the type 1 PTH/PTHrP receptor, thereby allowing PTHrP to inhibit bone morphogenetic protein 2 (BMP2) from enhancing gene expression of peroxisome proliferator-activated receptor gamma and the adipocyte-specific protein aP2 and from augmenting the accumulation of lipid. In the presence of BMP2, PTHrP or a protein kinase C (PKC) stimulator (phorbol ester) increased the expression of indexes of the osteoblast phenotype, including alkaline phosphatase, type I collagen, and osteocalcin, whereas a PKC inhibitor (chelerythrin chloride) inhibited PTHrP action. PTHrP and a phorbol ester increased gene expression of the BMP IA receptor, and both enhanced BMP2-dependent increases in promoter activity of the signaling molecule SMAD6. Overexpression of the BMP IA receptor facilitated the capacity of BMP2 to increase osteoblastogenesis in the absence of PTHrP and a dominant negative BMP IA receptor variant inhibited this effect of BMP2. These results demonstrate that PTHrP can direct osteoblastic, rather then adipogenic, commitment of mesenchymal cells, implicate PKC signaling in this activity, and show that PTHrP action involves enhanced gene expression of the BMP IA receptor, which facilitates BMP2 action in enhancing osteoblastogenesis in pluripotent mesenchymal cells.