Eficacia y seguridad del aceite de rosa mosqueta en las lesiones de los dedos provocadas por las punciones capilares para el control glucémico en niños con diabetes tipo 1; un ensayo clínico aleatorizado, abierto, controlado / Efficacy and safety of a rosehip seed oil extract in the prevention and treatment of skin lesions in the hands of patients with type 1 diabetes mellitus caused by finger prick blood glucose monitoring; a randomized, open-label, controlled clinical trial

Introducción: Evaluar la seguridad y eficacia de un extracto de aceite de rosa mosqueta en la prevención y tratamiento de las lesiones cutáneas en las manos de los pacientes con diabetes mellitus tipo 1 (DMT1) secundarias a las punciones digitales para el control glucémico. Pacientes y métodos: Estudio prospectivo, aleatorizado, controlado, abierto, con evaluadores ciegos e intervencionista en pacientes de edades entre 6 y 17 años con DMT1 y control intensivo de la glucemia con ≥ 7 punciones capilares diarias durante 12 días. Se evaluaron 3 variables principales (eritema, engrosamiento cutáneo, pérdida de la integridad cutánea) de la siguiente forma: 0: ausente, 1: leve, 2: moderado, 3: intenso. El estudio fue aprobado por el Comité Ético del hospital. Resultados: Se incluyó a 68 niños, por tanto, 136 manos: 80 recibieron aceite de rosa mosqueta y 56 fueron controles. Las características basales de los 2 grupos fueron similares. El 76,3% y el 78,6% presentaban alguna lesión dermatológica inicial, respectivamente. La mediana de valoración global final fue de 0,10 (0,03; 0,30) y de 0,06 (0,00; 0,23), en el grupo de aceite de rosa mosqueta y grupo control, respectivamente. Se encontró una mejoría estadísticamente significativa de la valoración global solo en el grupo control (p = 0,049). No se encontraron diferencias estadísticamente significativas para la comparación de medianas del resto de las variables principales. No se registraron efectos adversos. Conclusión: Se encontró una alta frecuencia de lesiones dermatológicas secundarias a punciones capilares digitales, la mayoría de las cuales fueron lesiones leves. La aplicación de aceite de rosa mosqueta fue segura y no supuso una mejoría en las lesiones dermatológicas

Introduction: This study was intended to assess the efficacy and safety of a rosehip seed oil (RHO) extract in the prevention and treatment of skin lesions in the hands of patients with type 1 diabetes mellitus (T1DM) caused by finger prick blood glucose monitoring. Patients and method: A prospective, randomized, controlled, open-label, rater-blinded trial in patients aged 6-17 years with T1DM and intensive blood glucose control (≥ 7 finger pricks daily) for 12 days. Three main variables (erythema, skin thickening, and loss of skin integrity) were assessed using a scale ranging from 0 (absent) to 3 (severe involvement). The study was approved by the ethics committee of the hospital. Results: Sixty-eight children, and thus 136 hands, were included; 80 hands received rosehip seed oil and 56 hands acted as controls. Baseline characteristics of both groups were similar, with 76.3% and 78.6% of the hands respectively showing skin lesions at study start. Median final global assessment was 0.10 (0.03; 0.30) in the group that received rosehip seed oil and 0.06 (0.00; 0.23) in the control group. A statistically significant improvement in global assessment was found in the control group (P=0.049). No significant differences were found when the medians of the other main variables were compared. No adverse effects were recorded. Conclusion: A high prevalence of skin lesions secondary to finger prick glucose monitoring, most of them mild lesions, was found at study start. Treatment with rosehip seed oil was safe and was not effective for improving skin lesions

Rumpel-Leede Phenomenon-An alarming rash with benign etiology in 4 healthy infants.

The Rumpel-Leede phenomenon (RLP) is a rare clinical presentation and in some cases shown to be related to serious systemic conditions. In children, it has been described in association with idiopathic thrombocytopenic purpura and Henoch-Schönlein purpura. We present a series of pediatric cases of RLP with mechanical etiologies that had a benign course. We propose minimal investigations for pediatric RLP cases who are systemically well and have a clear suggestive history of a mechanical cause.

Seizure-induced microvascular injury is associated with impaired neurovascular coupling and blood-brain barrier dysfunction.

OBJECTIVE: Blood-brain barrier (BBB) impairment, redistribution of pericytes, and disturbances in cerebral blood flow may contribute to the increased seizure propensity and neurological comorbidities associated with epilepsy. However, despite the growing evidence of postictal disturbances in microcirculation, it is not known how recurrent seizures influence pericytic membrane currents and subsequent vasodilation. METHODS: Here, we investigated successive changes in capillary neurovascular coupling and BBB integrity during recurrent seizures induced by 4-aminopyridine or low-Mg2+ conditions. To avoid the influence of arteriolar dilation and cerebral blood flow changes on the capillary response, we measured seizure-associated pericytic membrane currents, capillary motility, and permeability changes in a brain slice preparation. Arteriolar responses to 4-aminopyridine-induced seizures were further studied in anesthetized Sprague Dawley rats by using electrocorticography and tissue oxygen recordings simultaneously with intravital imaging of arteriolar diameter, BBB permeability, and cellular damage. RESULTS: Within the preserved vascular network in hippocampal slice cultures, pericytes regulated capillary diameter in response to vasoactive agents and neuronal activity. Seizures induced distinct patterns of membrane currents that contributed to the regulation of pericytic length. During the course of recurrent seizures, individual vasodilation responses eroded and BBB permeability increased, despite unaltered neurometabolic coupling. Reduced vascular responsiveness was associated with mitochondrial depolarization in pericytes. Subsequent capillary constriction preceded BBB opening, suggesting that pericyte injury mediates the breach in capillary integrity. In vivo findings were consistent with slice experiments, showing seizure-related neurovascular decoupling and BBB dysfunction in small cortical arterioles, accompanied by perivascular cellular injury despite normoxic conditions. SIGNIFICANCE: Our study presents a direct observation of gradually developing neurovascular decoupling during recurrent seizures and suggests pericytic injury as an inducer of vascular dysfunction in epilepsy.

Dermal capillary rarefaction as a marker of microvascular damage in patients with rheumatoid arthritis: Association with inflammation and disorders of the macrocirculation.

OBJECTIVE: Capillary rarefaction is observed in various cardiovascular diseases, yet it remains understudied in RA, a chronic inflammatory disease accompanied by excess cardiovascular risk. We quantified capillary density in RA patients and explored potential associations with macrocirculatory disorders, inflammation, and cardiovascular risk. METHODS: Dermal capillary density was assessed with nailfold capillaroscopy in RA and non-RA individuals, using specifically designed semiautomated software. Macrocirculation assessments included large artery stiffening, evaluated with PWV, and myocardial blood flow, calculated as cardiac index from impedance cardiography. Cardiovascular risk score was estimated from the Framingham Heart Study. RESULTS: The number of capillaries per visual field was lower in patients (n = 99) compared to controls (n = 35) (132.6 ± 30.3 vs 152.9 ± 25.2, P = .001). In the RA group, capillary density negatively correlated with CRP and PWV, and positively with HDL and cardiac index. In the multivariate analysis, CRP independently predicted capillary rarefaction (P = .044). Capillary density significantly correlated with cardiovascular risk, even after adjustment for inflammation (P = .030). CONCLUSION: Capillary rarefaction appears pronounced in RA and correlates with lower cardiac output, increased arterial stiffness, and cardiovascular risk. However, the associations with macrocirculatory disorders may be obscured by inflammation, which appears as the major contributor to capillary rarefaction in RA.

El futuro del tratamiento de las malformaciones capilares / The Future Of Treatment For Capillary Malformations

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Malformaciones capilares tratadas con aplicación secuencial de láser de colorante pulsado y Nd:YAG: estudio retrospectivo / Capillary Malformations Treated With Sequential Pulsed Dye and Nd:YAG Laser Therapy: A Retrospective Study

INTRODUCCIÓN Y OBJETIVO: Las malformaciones capilares son las malformaciones vasculares más frecuentes en la infancia. El tratamiento de elección sigue siendo el láser de colorante pulsado (LCP), sin embargo, la resolución completa con este habitualmente no se consigue, motivo por el que se siguen buscando otras alternativas terapéuticas. En este estudio comunicamos nuestra experiencia con el láser dual secuencial de LCP y Nd:YAG. MATERIAL Y MÉTODOS: Se efectuó un estudio retrospectivo y descriptivo de los pacientes con malformaciones capilares tratados con el láser dual de LCP y Nd:YAG desde 2006 hasta 2011. Cuatro dermatólogos valoraron el grado de eficacia en una escala del 10 al 0. Se analizó la posibilidad de factores predictores de mejor respuesta al tratamiento: sexo, color de la lesión, existencia de hipertrofia asociada y tamaño de la malformación. Se recogieron igualmente los efectos secundarios. RESULTADOS: Se incluyeron 71 pacientes, presentando el conjunto de ellos una mejoría estadísticamente significativa tras el tratamiento. Las malformaciones de coloración violácea que tenían hipertrofia asociada y las de menor tamaño se asociaron con una mejor respuesta. Se produjeron efectos adversos en un 26,76% de los pacientes, siendo la presencia de zonas atróficas puntuales el más frecuente. CONCLUSIONES: Consideramos que el láser dual de LCP y Nd:YAG es una alternativa eficaz para el tratamiento de malformaciones capilares en paciente seleccionados

INTRODUCTION AND OBJECTIVE: Capillary malformations are the most common vascular malformations in childhood. The current treatment of choice is pulsed dye laser (PDL) therapy, but this frequently does not result in complete resolution. The search for alternative treatment strategies thus continues. In this study we describe our experience with the use of sequential dual-wavelength PDL and Nd:YAG laser therapy in patients with capillary malformations. MATERIAL AND METHODS: We conducted a retrospective, descriptive study of patients with capillary malformations treated with dual-wavelength PDL and Nd:YAG laser therapy between 2006 and 2011. Four dermatologists rated the effectiveness of treatment on a scale of 10 to 0. We also investigated the potential value of the following factors as predictors of better treatment response: sex, malformation size and color, and presence of associated hypertrophy. Adverse effects were also analyzed. RESULTS: We studied 71 patients and most of them experienced a statistically significant improvement after treatment. More favorable responses were observed for violaceous malformations, lesions with associated hypertrophy, and smaller lesions. Adverse effects were reported for 26.76% of patients, and the most common effect was the appearance of isolated areas of skin atrophy. CONCLUSIONS: We consider that sequential dual-wavelength PDL and ND:YAG laser therapy is an effective alternative for treating capillary malformations in selected patients

Reducing damage to the periosteal capillary network caused by internal fixation plating: An experimental study.

BACKGROUND: The importance of the periosteum in fracture healing is well-known. Preserving periosteal vascularisation is essential during internal plate fixation of fractures. METHODS: This was an experimental randomised, controlled animal study on nine sheep. Standard dynamic compression plate (DCP) and four different newly designed reefed plates, with different plate-bone contact surface areas and different reef directions, were fixated on to the tibia or radius. After two weeks the plates were removed and the underlying periosteum was analysed. Blood vessels were marked by immunohistochemical staining (CD31 and CD34), microphotographs were taken and blood vessels counted to calculate blood vessel density. RESULTS: Median blood vessel density beneath the standard plate was significantly lower than in the intact periosteum (18.0 vs 27.7mm(3)/cm(3)). Blood vessel density in the periosteum beneath plates with reefs was significantly increased compared with the intact periosteum, and was highest beneath the plate with the lowest bone-plate contact area and crosswise reefs (51.5mm(3)/cm(3)), followed by plates with transverse, oblique and longitudinal reefs, respectively. The direction of the reefs did not have much influence on the periosteal capillary network. Lower contact surface area seems to be the main factor that increases blood vessel density beneath the plates. CONCLUSIONS: The results show that plates with lower contact surface area stimulate angiogenesis in the underlying periosteum, which results in much higher blood vessel density compared with standard DCP. A randomised clinical trial is needed to prove the clinical relevance of these findings.

The Biomechanics of Cranial Forces During Figure Skating Spinning Elements.

Several facets of figure skating, such as the forces associated with jumping and landing, have been evaluated, but a comprehensive biomechanical understanding of the cranial forces associated with spinning has yet to be explored. The purpose of this case study was to quantify the cranial rotational acceleration forces generated during spinning elements. This case report was an observational, biomechanical analysis of a healthy, senior-level, female figure skating athlete who is part of an on-going study. A triaxial accelerometer recorded the gravitational forces (G) during seven different spinning elements. Our results found that the layback spin generated significant cranial force and these forces were greater than any of the other spin elements recorded. These forces led to physical findings of ruptured capillaries, dizziness, and headaches in our participant.

Microangiopatía trombótica asociada a tacrolimus en trasplante pulmonar / Thrombotic Microangiopathy Associated With Tacrolimus in Lung Transplantation

La microangiopatía trombótica (MAT) es una complicación infrecuente asociada a los anticalcineurínicos en el trasplante pulmonar, independiente de la enfermedad de base de los pacientes trasplantados. Habitualmente se presenta como formas incompletas, lo que dificulta el diagnóstico, que suele ser tardío, provocando irreversibilidad de las lesiones. Es independiente del tiempo de trasplante y en muchos casos existe infección concomitante, lo que tiende a ocultar el diagnóstico. Los casos presentados comparten el agente causal y la presencia de infección concomitante. El tratamiento ha variado en los últimos años, recomendándose la plasmaféresis o, más recientemente, el anticuerpo eculizumab. No obstante, la retirada o cambio del anticalcineurínico causante es la medida más coste-efectiva. La MAT podría tratarse de una entidad infradiagnosticada a tener en cuenta en pacientes trasplantados

Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients

Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.

BACKGROUND: The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis. METHODS: We examined the alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 ± 17.6 years old) using double immunostaining for the α2(IV) and α5(IV) chains of type IV collagen, and examining the ultrastructural alterations by transmission electron microscopy (TEM) and low-vacuum scanning electron microscopy (LV-SEM). RESULTS: The GBM of IgA nephropathy cases showed various morphological and qualitative alterations. In the TEM findings, thinning, gaps, rupture, thickening with a lamellar and reticular structure and double contours were detected in the GBM. Double immunostaining for α5(IV) and α2(IV) showed thickening of the GBM with reduced α5(IV) and increased α2(IV), or mosaic images of α5(IV) and α2(IV), and holes, fractures, spiny projections and rupture of α5(IV) in the GBM. In addition, LV-SEM showed an etched image and multiple holes in a widening and wavy GBM. These findings might be associated with the development of a brittle GBM in IgA nephropathy. CONCLUSION: Glomerular basement membrane alterations were frequently noted in IgA nephropathy, and were easily evaluated by double immunostaining for α2(IV) and α5(IV) of type IV collagen and LV-SEM. The application of these analyses to human renal biopsy specimens may enhance our understanding of the alterations of the GBM that occur in human glomerular diseases.

A multilevel hierarchical finite element model for capillary failure in soft tissue.

Bruising, the result of capillary failure due to trauma, is a common indication of abuse. However, the etiology of capillary failure has yet to be determined as the scale change from tissue to capillary represents several orders of magnitude. As a first step toward determining bruise etiology, we have developed a multilevel hierarchical finite element model (FEM) of a portion of the upper human arm using a commercial finite element tool and a series of three interconnected hierarchical submodels. The third and final submodel contains a portion of the muscle tissue in which a single capillary is embedded. Nonlinear, hyperelastic material properties were applied to skin, adipose, muscle, and capillary wall materials. A pseudostrain energy method was implemented to subtract rigid-body-like motion of the submodel volume experienced in the global model, and was critical for convergence and successful analyses in the submodels. The deformation and hoop stresses in the capillary wall were determined and compared with published capillary failure stress. For the dynamic load applied to the skin of the arm (physiologically simulating a punch), the model predicted that approximately 8% volume fraction of the capillary wall was above the reference capillary failure stress, indicating bruising would likely occur.

Lung capillary injury and repair in left heart disease: a new target for therapy?

The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

Fluorescence microangiography for quantitative assessment of peritubular capillary changes after AKI in mice.

AKI predicts the future development of CKD, and one proposed mechanism for this epidemiologic link is loss of peritubular capillaries triggering chronic hypoxia. A precise definition of changes in peritubular perfusion would help test this hypothesis by more accurately correlating these changes with future loss of kidney function. Here, we have adapted and validated a fluorescence microangiography approach for use with mice to visualize, analyze, and quantitate peritubular capillary dynamics after AKI. A novel software-based approach enabled rapid and automated quantitation of capillary number, individual area, and perimeter. After validating perfusion in mice with genetically labeled endothelia, we compared peritubular capillary number and size after moderate AKI, characterized by complete renal recovery, and after severe AKI, characterized by development of interstitial fibrosis and CKD. Eight weeks after severe AKI, we measured a 40%±7.4% reduction in peritubular capillary number (P<0.05) and a 36%±4% decrease in individual capillary cross-sectional area (P<0.001) for a 62%±2.2% reduction in total peritubular perfusion (P<0.01). Whereas total peritubular perfusion and number of capillaries did not change, we detected a significant change of single capillary size following moderate AKI. The loss of peritubular capillary density and caliber at week 8 closely correlated with severity of kidney injury at day 1, suggesting irreparable microvascular damage. These findings emphasize a direct link between severity of acute injury and future loss of peritubular perfusion, demonstrate that reduced capillary caliber is an unappreciated long-term consequence of AKI, and offer a new quantitative imaging tool for understanding how AKI leads to future CKD in mouse models.

Proximal nail fold intralesional steroid injection responsible for Hoigné syndrome.

BACKGROUND: Hoigné syndrome is the most common name given to a condition which has been called in different ways. OBJECTIVE: We want to show that an intralesional injection of prednisolone into the proximal nail fold may produce dorsal pain, dyspnoea and headaches within the 2 min following the injection and to explain the pathophysiology of his condition. METHODS: We studied the different drugs responsible for Hoigné syndrome by comparing the size of the crystals taking into account the diameter of pulmonary capillaries. The drug Company informed us that the size of the microcrystals were 2-4 µm vs. the 8 µm on average of the diameter of the pulmonary capillaries. CONCLUSION: All the symptoms of Hoigné syndrome can be explained, especially the neuropsychiatric and neuropulmonary ones. Therefore, dermatologists should be aware of this phenomenon when they inject steroids in psoriatic nail patients.

Alveolar oxygen tension and angio-architecture of the distal adult lung.

The present study demonstrates the fine structure of pulmonary capillaries first injured and then undergoing growth in response to a change in the ambient alveolar oxygen tension. Breathing a high fraction of inspired oxygen (FiO2 0.75) triggers restriction by endothelial cell injury and effacement leading to segment narrowing and shortening and segment loss as demonstrated by a fall in density. Subsequently, breathing a relatively low fraction (FiO2 0.21) triggers capillary assembly (angiogenesis), which reverses the changes. The data underscore the structural reprogramming (reduction and restoration) of pulmonary capillaries in response to significant shifts in oxygen tension.

Deep vascular imaging in wounds by two-photon fluorescence microscopy.

Deep imaging within tissue (over 300 µm) at micrometer resolution has become possible with the advent of two-photon fluorescence microscopy (2PFM). The advantages of 2PFM have been used to interrogate endogenous and exogenous fluorophores in the skin. Herein, we employed the integrin (cell-adhesion proteins expressed by invading angiogenic blood vessels) targeting characteristics of a two-photon absorbing fluorescent probe to image new vasculature and fibroblasts up to ≈ 1600 µm within wound (neodermis)/granulation tissue in lesions made on the skin of mice. Reconstruction revealed three dimensional (3D) architecture of the vascular plexus forming at the regenerating wound tissue and the presence of a fibroblast bed surrounding the capillaries. Biologically crucial events, such as angiogenesis for wound healing, may be illustrated and analyzed in 3D on the whole organ level, providing novel tools for biomedical applications.

Effect of tamsulosin on bladder microcirculation in rat model of bladder outlet obstruction using pencil lens charge-coupled device microscopy system.

OBJECTIVE: To determine the effect of tamsulosin hydrochloride on blood flow in the submucosal capillaries of the bladder (SCB) in a rat model of bladder outlet obstruction (BOO) using a pencil lens charge-coupled device microscopy system. MATERIALS AND METHODS: BOO was established in rats by partial ligature of the proximal urethra and was maintained for 2 weeks. Tamsulosin or saline (control) was subcutaneously administered using an osmotic pump for 2 weeks immediately after surgery. The pencil lens charge-coupled device microscopy system was used to visualize the bladder microcirculation and quantitatively assess the blood flow in the SCB by measuring the velocity of the blood flow at the base and dome of the bladder. The blood flow in the SCB of the sham-operated rats, control BOO rats, and tamsulosin-treated BOO rats was compared. RESULTS: The blood flow in the SCB was significantly greater at the base than at the dome of the bladder. The reduction in blood flow through the SCB at the base and dome of the bladder was more significant in the BOO rats than in the sham-operated rats. However, after pretreatment with tamsulosin, the BOO rats showed a significant increase in blood flow through the SCB at the base and dome of the bladder compared with that of the control rats. The pencil lens charge-coupled device microscopy system image showed that the BOO rats had chronic ischemic capillary injury, which was ameliorated by tamsulosin. CONCLUSION: The results of the present study suggest that tamsulosin hydrochloride protects the SCB from ischemic injury after BOO.

Theoretical microbubble dynamics in a viscoelastic medium at capillary breaching thresholds.

In order to predict bioeffects in contrast-enhanced diagnostic and therapeutic ultrasound procedures, the dynamics of cavitation microbubbles in viscoelastic media must be determined. For this theoretical study, measured 1.5 to 7.5 MHz pulse pressure waveforms, which were used in experimental determinations of capillary breaching thresholds for contrast-enhanced diagnostic ultrasound in a rat kidney, were used to calculate cavitation nucleated from contrast agent microbubbles. A numerical model for cavitation in tissue was developed based on the Keller-Miksis equation (a compressible extension of the Rayleigh-Plesset equation for spherical bubble dynamics), with a Kelvin-Voigt constitutive relation. From this model, the bubble dynamics corresponding to the experimentally obtained capillary breaching thresholds were determined. Values of the maximum radius and temperature corresponding to previously determined bioeffect thresholds were computed for a range of ultrasound pulses and bubble sizes for comparison to inertial cavitation threshold criteria. The results were dependent on frequency, the gas contents, and the tissue elastic properties. The bioeffects thresholds were above previously determined inertial cavitation thresholds, even for the tissue models, suggesting the possibility of a more complex dosimetry for capillary injury in tissue.