Role of collagen and immunostaining for TGF-β in the clinical andmicroscopic findings of pyogenic granuloma and peripheral ossifying fibroma

Background: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-β) in the clinical and microscopic findings of PG and POF. Material and Methods: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-β) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). Results: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-β+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-β suffered from modifications by the time of evolution and the size of the lesion. Conclusions: Although PG and POF are reactive gingival lesions, the expression of TGF-β and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components. (AU)

Efficacy of an oral collagen therapy compared with intra-articular therapies (hyaluronic acid and platelet-rich plasma) to treat knee osteoarthritis / Eficacia de una terapia oral de colágeno comparada con terapias intraarticulares (ácido hialurónico y plasma rico en plaquetas) en el manejo de la osteoartritis de rodilla

Introducción: la osteoartritis es una enfermedad crónica y progresiva que afecta a más del 30 % de las personas mayores de 60 años. Actualmente, se reconoce la osteoartritis como una enfermedad multifactorial. Se emplean varios tratamientos conservadores en el manejo de la osteoartritis de rodilla (AINE, analgésicos y terapias intraarticulares). Se realizó un ensayo clínico aleatorizado para determinar si una terapia a base de 10 g de colágeno hidrolizado y 100 mg de fucoidano (Hydroidan pro, Acten, Suiza) era más efectiva que las terapias intraarticulares. Métodos: se dividió a los pacientes en 3 grupos. El primero recibió 23 g de ACTEN® cada día durante 3 meses. Los otros grupos recibieron una única inyección intraarticular de ácido hialurónico (5 ml) o plasma rico en plaquetas (3 ml). Se emplearon las escalas WOMAC, SF-12 y VAS para valorar el dolor al inicio, 4, 12 y 24 semanas después. Resultados: se incluyó a 108 pacientes con osteoartritis de rodilla de grado II-III que participaron en un estudio de seguimiento de 24 semanas de duración. La edad media fue de 57 años (53-65). Los 3 grupos rebajaron la puntuación en el grupo WOMAC (p < 0,001). El grupo que recibió colágeno y fucoidano obtuvo puntuaciones más bajas en las escalas WOMAC y VAS que los grupos que recibieron ácido hialurónico y plasma rico en plaquetas a las 24 semanas (p < 0,001). Conclusiones: el colágeno y el fucoidano tomado por vía oral, a diario, y durante 12 semanas parecen cosechar mejores resultados en las escalas WOMAC y VAS que las terapias intraarticulares a base de ácido hialurónico o plasma rico en plaquetas. Se debería de intentarse combinar terapias orales e intraarticulares para determinar su perfil de eficacia.(AU)

Introduction: osteoarthritis is a chronic and progressive disease. It affects over 30 % of people older than 60. Osteoarthri-tis is currently recognized as a multifactorial disease. Various conservative treatments are used in the management of kneeosteoarthritis (NSAIDs, analgesics, and intra-articular therapy). We conducted a randomized clinical trial to determine if a10 g therapy of hydrolyzed collagen along with 100 mg fucoidan (Hydroidan pro, Acten, Switzerland) is more effective thanintra-articular therapies.Methods: we divided patients into 3 groups. The first group received 23 g of ACTEN®, daily, for 3 months. The other groupsreceived a single intra-articular injection of hyaluronic acid (5 ml) or platelet-rich plasma (3 ml). We used the WOMAC scale,the SF-12 scale, and the VAS for pain at baseline, and 4, 12, and 24 weeks later.Results: we enrolled 108 patients with grade II-III knee osteoarthritis who underwent a 24-week follow-up study. The meanage was 57 years (53-65). The three groups showed low scores in the WOMAC group (p < 0.001). The collagen with fucoid-an group had lower WOMAC and VAS scores compared with the hyaluronic acid and platelet-rich plasma groups at 24weeks (p < 0.001).Conclusions: collagen along with fucoidan taken orally, daily, for 12 weeks seem to have better results in the WOMACand VAS scales compared with intra-articular therapies such as hyaluronic acid or platelet-rich plasma. Combined oral andintra-articular therapies should be tried to determine their efficacy profile.(AU)

Osteogénesis Imperfecta: Entre la ficción y la realidad / Imperfect Osteogenesis: Between Fiction and Reality

Los largometrajes han sido utilizados como una herramienta de aprendizaje llamativa en el campo de la salud, esto debido a que ciertas enfermedades que suelen ser raras dentro de la población se prestan para desarrollar una historia en base a las mismas. La Osteogénesis imperfecta conocida también como la enfermedad de los huesos de cristal, es un trastorno genético bastante diverso, si bien el 90 % de los casos se presentan con mutaciones de herencia de tipo autosómicas dominantes, un 10 % restante corresponde a mutaciones autosómicas recesivas o de causa desconocida. En el presente trabajo hemos generado una recopilación de aspectos relevantes sobre esta enfermedad correlacionando con la trama de dos trabajos cinematográficos, Frágiles y El protegido; esto con el fin de analizarlo como una posible herramienta para el aprendizaje de esta enfermedad y de otras patologías de carácter genético. (AU)

Feature films have been used as a striking learning tool in the field of health, this because certain diseases that are usually rare within the population lend themselves to developing a story based on them. Imperfect Osteogenesis also known as crystal bone disease, is a fairly diverse genetic disorder, although 90 % of cases present with autosomal dominant inherited mutations, the remaining 10 % corresponds to autosomal recessive mutations or of unknown cause. In the present work we have generated a compilation of relevant aspects about this disease correlating with the plot of two cinematographic works, Fragile and The Protected; this in order to analyze it as a possible tool for learning about this disease and other pathologies of a genetic nature. (AU)

Tratamiento mediante suplementación oral o fármacos sistémicos del envejecimiento cutáneo. Revisión narrativa de la literatura / Oral Supplementation and Systemic Drugs for Skin Aging: A Narrative Review

El envejecimiento cutáneo está influido por factores intrínsecos y extrínsecos y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son sobre todo tópicos o son procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen a mujeres de manera mayoritaria, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos o fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos, como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos, presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo parece ser el tratamiento con agentes senolíticos o senomórficos dirigidos específicamente contra células cutáneas senescentes. (AU)

Skin aging is influenced by intrinsic and extrinsic factors and involves multiple pathogenic mechanisms. The most widely used treatments are topical products and minimally invasive procedures. Evidence on the benefits of systemic therapy is limited for several reasons: Reliance on mostly small and predominantly female samples, short study durations, methodologic heterogeneity, and a lack of consensus on which outcome measures are clinically relevant. Furthermore, systemic drugs and oral supplements are not without adverse effects. Oral hydrolyzed collagen and oral hyaluronic acid are well tolerated, and numerous clinical trials show they can mitigate some signs of skin aging. Low-dose oral isotretinoin is another option, but it has a higher risk of adverse effects. Evidence is lacking on the effects of the many dietary supplements on offer, such as vitamins, flavonoids, plant extracts, and trace elements. The future of skin aging management would appear to lie in the use of senolytic and senomorphic agents targeting senescent cells in the skin. (AU)

[Translated article] Oral Supplementation and Systemic Drugs for Skin Aging: A Narrative Review / Tratamiento mediante suplementación oral o fármacos sistémicos del envejecimiento cutáneo. Revisión narrativa de la literatura

Skin aging is influenced by intrinsic and extrinsic factors and involves multiple pathogenic mechanisms. The most widely used treatments are topical products and minimally invasive procedures. Evidence on the benefits of systemic therapy is limited for several reasons: reliance on mostly small and predominantly female samples, short study durations, methodologic heterogeneity, and a lack of consensus on which outcome measures are clinically relevant. Furthermore, systemic drugs and oral supplements are not without adverse effects. Oral hydrolyzed collagen and oral hyaluronic acid are well tolerated, and numerous clinical trials show they can mitigate some signs of skin aging. Low-dose oral isotretinoin is another option, but it has a higher risk of adverse effects. Evidence is lacking on the effects of the many dietary supplements on offer, such as vitamins, flavonoids, plant extracts, and trace elements. The future of skin aging management would appear to lie in the use of senolytic and senomorphic agents targeting senescent cells in the skin. (AU)

El envejecimiento cutáneo está influido por factores intrínsecos y extrínsecos y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son sobre todo tópicos o son procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen a mujeres de manera mayoritaria, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos o fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos, como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo parece ser el tratamiento con agentes senolíticos o senomórficos dirigidos específicamente contra células cutáneas senescentes. (AU)

Eficacia de un complemento alimenticio con colágeno hidrolizado / Efficacy of a food supplement containing hydrolyzed collagen on the improvement of clinical indices in knee osteoarthritis

La osteoartritis (OA) de rodilla es una de las principales causas de dolor y discapacidad en todo el mundo con un impacto socioeconómico importante, que afecta a la calidad de vida de los pacientes y repercute negativamente en el Sistema Nacional de Salud.El objetivo del estudio ha sido evaluar el efecto de un complemento alimenticio con péptidos de colágeno de bajo peso molecular sobre los síntomas de la OA (dolor y limitación funcional).Se realizó un ensayo clínico aleatorizado, doble ciego, controlado con placebo y paralelo de dos brazos con un periodo de seguimiento de 6 meses. El estudio incluyó a 120 pacientes con diagnóstico de gonartrosis grado 2 o 3 y artralgia, con una puntuación mínima de 50 mm (rango de 0 a 100 mm) en la escala visual analógica (EVA) de dolor. Sesenta pacientes fueron asignados al grupo experimental (GrA), que recibió 1 sobre al día del complemento alimenticio que contenía colágeno hidrolizado; el otro grupo (n=60) recibió 1 sobre al día con placebo (GrP). Los sujetos fueron evaluados en una visita inicial, antes del tratamiento (T0) y en la visita final (T1) al concluir los 6 meses del periodo de seguimiento.Ambos grupos de tratamiento fueron comparables en la visita inicial (T0). En la visita final (T1), el GrA (comparado con el GrP), experimentó una disminución estadísticamente significativa en la intensidad del dolor (escala visual analógica, EVA) y la puntuación recogida en el índice algofuncional de Lequesne. También disminuyeron en T1 las cifras de proteína C reactiva (PCR) y la velocidad de sedimentación globular (VSG) en el GrA. No se observaron efectos adversos durante el estudio.El CH mejoró los síntomas de dolor osteoarticular y la capacidad funcional en pacientes con gonartrosis, con un buen perfil de tolerancia y seguridad. (AU)

Knee osteoarthritis is a leading cause of pain and disability worldwide, having a considerable socioeconomical impact on both the health-care system and the patient quality of life.The aim of the study was to assess the effect of a food supplement containing low molecular collagen peptides in the symptoms of osteoarthritis (OA) (pain and functional limitation).A 6-month, randomized, double-blind, placebo-controlled and parallel two-arm study was conducted in 120 patients diagnosed with grade 2 or 3 OA and pain, with a minimum score of 50 mm (range 0 to 10 mm) in the visual analogic scale (VAS) for pain. The investigational product (n=60) or placebo (n=60) was taken once daily, and subjects were assessed at baseline (T0, pre-treatment) and after a follow-up period of 6 months (T1).Both groups were comparable at baseline. Compared to placebo, changes in VAS, Lequesne algofunctional index (LAI), C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) after six months of treatment, were significant lower in the group of patients taking the active product. No adverse effects were reported during the study.The HC improved the osteoarticular pain and physical function in patients with knee OA. Furthermore, it was well tolerated and satisfactory; and showed adequate results in terms of safety and acceptability of HC. The food supplement may be complementary of drug therapy in knee osteoarthritis. (AU)

The ABCD grading system in assessment of corneal cross-linking effect in keratoconus with different cone locations

Purpose: The aim of this study was to analyse the postoperative corneal cross-linking results of corneal parameters and the ABCD grading system, depending on the cone location.MethodsThirty eyes of 25 patients with keratoconus (KC), who received the corneal cross-linking (CXL) treatment, were included in this study. The exclusion criteria were: patients under 18 years of age, corneal pachymetry less than 400 μm, corneal scarring, history of ocular trauma, history of ocular surgery, and corneal pathology other than KC. Patients were examined at the baseline visit, and followed-up at three, six, and twelve months after the CXL. All patients underwent visual acuity and Scheimpflug tomography at all visits. Progression parameters, keratometries, and ABCD grading were compared between the visits. Patients were classified into two groups: central and paracentral cones group (within the central 5 mm corneal zone) and peripheral cones group (outside the central 5 mm corneal zone), based on X-Y coordinates of maximal keratometry (Kmax).ResultsParameter A remained relatively stable throughout the follow-up period in both groups. Parameter B and parameter C showed a significant increase in both groups postoperatively. Parameter D showed stability at the 6-month post-CXL visit in the peripheral KC group, while the central and paracentral KC group showed improvement at the 12-month post-CXL visit.ConclusionThere was no significant difference in the postoperative response between different cone locations in the ABCD grading system, when classifying according to the Kmax, except an earlier recovery of the parameter D in peripherally located cones. (AU)

Corilagin attenuates airway inflammation and collagen deposition in ovalbumin-induced asthmatic mice

Objective: To investigate the effects of corilagin on inflammation and collagen deposition in ovalbumin (OVA)-induced asthma mouse model and uncover the mechanism. Methods: We constructed a mouse model of OVA-induced asthma. Enzyme-linked-immunosorbent serologic assays were conducted to detect the effects of corilagin on cytokines and Immunoglobulin E (IgE) production. Hematoxylin and eosin staining was used to show pathological features in lung tissues. Masson trichrome assay was used to examine collagen deposition. In addition, the lung function was detected by mouse lung function apparatus. Immunoblot was used to confirm the mechanism. Results: Corilagin alleviates OVA-induced cytokine and IgE production. In addition, corilagin alleviates OVA-induced pathological changes and collagen deposition in lung tissues. Corilagin also suppressed airway resistance and lung function in mice. Mechanically, corilagin activated the adenosine monophosphate-activated protein kinase (AMPK) pathway in lung tissues. Conclusion: Corilagin attenuates airway inflammation and collagen deposition in OVA-induced asthmatic mice via AMPK pathway (AU)

Hypertension secondary to nitric oxide depletion produces oxidative imbalance and inflammatory/fibrotic outcomes in the cornea of C57BL/6 mice

Arterial hypertension (AH) leads to oxidative and inflammatory imbalance that contribute to fibrosis development in many target organs. Here, we aimed to highlight the harmful effects of severe AH in the cornea. Our experimental model was established by administration of NG-nitro-L-arginine-methyl-ester (L-NAME) to C57BL/6 mice, which were monitored weekly for arterial blood pressure and intraocular pressure (IOP). Morphological studies of ocular tissues were accompanied by analyses of reactive oxygen species generation, and localization/expression of NAPDH oxidase isoforms (NOX1, NOX2, NOX4) and inflammatory biomarkers (PPARα, PPARγ, IL-1β, IL-6, IL-10, TNF-α, and COX-2). Masson’s trichrome and Sirius Red staining were used to explore the fibrotic status of the cornea. The expression of collagen isoforms (COL1α1, COL1α2, COL3α1, COL4α1, COL4α2) and relevant metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were also quantified to evaluate the participation of collagen metabolism in AH-related corneal damage. Hypertensive animals showed an increase in IOP values, and a thinner cornea compared with normotensive controls. Moreover, AH increased NADPH oxidase activity and reactive oxygen species generation in the cornea, which was accompanied by transcriptional upregulation of NOX isoforms and inflammatory biomarkers, while reducing PPAR expression. L-NAME-treated animals also developed corneal fibrosis with overexpression of collagen isoforms and reduction of factors responsible for collagen degradation. This is the first study reporting structural changes in the cornea and elevated IOP in L-NAME-treated mice. Overexpression of the NADPH oxidase system and collagen deposition might play a substantial role in the pathogenic mechanisms contributing to ocular disturbances in a context of severe hypertension. (AU)

Revisión de la literatura sobre la evidencia disponible actualmente para el manejo de las queratitis infecciosas con PACK-CXL / Review of the literature on the currently available evidence for the management of infectious keratitis with PACK-CXL

Las queratitis infecciosas (QI) son una de las causas más comunes de ceguera a nivel mundial, especialmente en países en vías de desarrollo, y puede llegar a representar del 5,1 al 32,3% de todas las indicaciones de queratoplastia penetrante. Sin embargo, realizar una queratoplastia terapéutica «en caliente» está asociado con una mayor incidencia de recurrencia de la QI y rechazo del injerto. El tratamiento estándar incluye antimicrobianos (ATM) de amplio espectro y, una vez identificado el patógeno causante y el antibiograma, continuar con un tratamiento dirigido, según la sensibilidad del germen. La aparición de cepas multirresistentes a los ATM está aumentando progresivamente a un ritmo alarmante en los últimos tiempos. Asimismo, la diversidad de los microorganismos causantes (bacterias, hongos, parásitos, virus) dificulta en ocasiones la realización de un diagnóstico clínico correcto, retrasando el inicio de un tratamiento efectivo. Se estima que solo un 50% de los ojos tendrá un buen resultado visual si se retrasa la terapia. En definitiva, todos estos factores hacen que sea muy importante la identificación de alternativas al tratamiento ATM. Por las propiedades ATM del cromóforo fotoactivado (riboflavina) y la luz ultravioleta de longitud de onda 200-400nm, utilizada en múltiples aplicaciones médicas y no médicas para la desinfección, se ha propuesto el cromóforo fotoactivado para el cross-linking corneal en el tratamiento de las QI, como una herramienta adicional en el arsenal terapéutico de las QI. Debe diferenciarse del cross-linking empleado para el manejo del queratocono progresivo. El objetivo de esta revisión es actualizar la evidencia disponible sobre la eficacia y seguridad del cromóforo fotoactivado para el cross-linking en las QI (AU)

Infectious keratitis (IK) is one of the most common causes of monocular blindness worldwide, especially in developing countries, and may account for 5.1 to 32.3% of all indications for penetrating keratoplasty (PK). However, performing a therapeutic PK on a “hot eye” is associated with a higher incidence of IK recurrence and graft rejection. Standard treatment includes antimicrobials (ATM) and, once the causative pathogen has been identified, must be continued with targeted treatment, depending on antibiogram sensitivity. However, appearance of multiresistant strains to ATM is progressively increasing at an alarming rate. Besides that, the diversity of the causative microorganisms (bacteria, fungi, parasites, viruses) may hinder the clinical diagnosis and secondarily the proper treatment from the beginning. It is estimated that only 50% of eyes will have a good visual result if the correct therapy is delayed. All these factors make the identification of alternatives to ATM treatment of paramount importance. Due to the ATM properties of photoactivated chromophore (riboflavin) and ultraviolet light of wavelength 200-400nm, used in multiple medical and non-medical applications for disinfection, photoactivated chromophore for corneal cross-linking (CXL) of IK, as an addition to the therapeutic arsenal for the management of IK has been proposed. It must be differentiated from CXL used for the management of progressive keratoconus. The objective of this review is to update the available evidence on the efficacy and safety of photoactivated chromophore for corneal CXL in IKs (AU)

Modulatory activity of a bovine hydrolyzed collagen-hydroxyapatite food complex on human primary osteoblasts after simulating its gastrointestinal digestion and absorption / Actividad moduladora de un complejo alimentario de colágeno hidrolizado e hidroxiapatita bovinos sobre osteoblastos primarios humanos tras simular su digestión gastrointestinal y su absorción

Introduction: osteoporosis is the most prevalent bone disease and one of the main causes of chronic disability in middle and advanced ages. Conventional pharmacological treatments are still limited, and their prolonged use can cause adverse effects that motivate poor adherence to treatment. Nutritional strategies are traditionally based on supplementing the diet with calcium and vitamin D. Recent studies confirm that the results of this supplementation are significantly improved if it is accompanied by the intake of oral hydrolyzed collagen. Objective: to evaluate the possible in vitro osteogenic activity of a peptide-mineral complex formed by bovine hydrolyzed collagen and bovine hydroxyapatite (Phoscollagen®, PHC®). Methods: the digestion and absorption of PHC® were simulated using the dynamic gastrointestinal digester of AINIA and Caco-2 cell model, respectively. Primary cultures of human osteoblasts were treated with the resulting fraction of PHC® and changes were evaluated in the proliferation of preosteoblasts and in the mRNA expression of osteogenic biomarkers at different stages of osteoblast maturation: Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin (OC) and type I collagen (ColA1). Results: an increase in preosteoblastic proliferation was observed (p ≤ 0,05). No changes were detected in the biomarkers of osteoblasts with 5 days of differentiation, but with 14 days, registering in this case an increase in Runx2 (p = 0.0008), ColA1 (p = 0.035), OC (p = 0.027) and ALP (without significance). Conclusion: these results show that PHC® peptide-mineral complex stimulates the activity of mature osteoblasts, being capable of promoting bone formation (AU)

Introducción: la osteoporosis es la enfermedad ósea más prevalente y una de las principales causas de discapacidad crónica en las edades medias y avanzadas. Los tratamientos farmacológicos convencionales aún son limitados y su uso prolongado puede provocar efectos adversos que motiven baja adherencia al tratamiento. Las estrategias nutricionales se basan tradicionalmente en suplementar la dieta con calcio y vitamina D. Estudios recientes confirman que los resultados de esta suplementación mejoran significativamente si se acompaña de la ingesta de colágeno hidrolizado oral. Objetivo: evaluar la posible actividad osteogénica in vitro de un complejo péptido-mineral formado por colágeno hidrolizado e hidroxiapatita bovinos (Phoscollagen®, PHC®). Métodos: se simuló la digestión y absorción de PHC® utilizando el digestor dinámico gastrointestinal de AINIA y el modelo celular Caco-2, respectivamente. Cultivos primarios de osteoblastos humanos se trataron con la fracción resultante de PHC® y se evaluaron los cambios en la proliferación de los preosteoblastos y en la expresión del ARNm de los biomarcadores osteogénicos en diferentes etapas de maduración de los osteoblastos: factor de transcripción 2 relacionado con Runt (Runx2), fosfatasa alcalina (ALP), osteocalcina (OC) y colágeno tipo I (ColA1). Resultados: se observó un incremento de la proliferación preosteoblástica (p ≤ 0,05). No se detectaron cambios en los biomarcadores de osteoblastos con 5 días de diferenciación, pero sí con 14 días, registrándose un aumento de Runx2 (p = 0,0008), ColA1 (p = 0,035), OC (p = 0,027) y ALP (sin significancia). Conclusión: estos resultados muestran que el complejo péptido-mineral PHC® estimula la actividad de osteoblastos maduros, siendo susceptible de promover la formación ósea (AU)

Eficacia de las infiltraciones con colágeno en el dolor pélvico causado por cicatrices de episiotomía y cesáreas. Ensayo clínico piloto aleatorizado / Efficacy of collagen infiltrations in the pelvic pain caused by episiotomy and caesarean scars. Pilot randomized clinical trial

Introducción y objetivos: El dolor pélvico es un síntoma frecuente de consulta en las unidades de rehabilitación de suelo pélvico. El objetivo de este estudio fue evaluar la eficacia de las infiltraciones con colágeno en el dolor y el aspecto de las cicatrices de desgarros perineales, episiotomías y/o cesáreas. Material y métodos: Ensayo clínico piloto aleatorizado, controlado y simple ciego. Las pacientes del grupo control (GC) recibieron el tratamiento convencional de rehabilitación. De forma adicional, las del grupo intervención (GI) recibieron de 3 a 5 infiltraciones de colágeno. Las pacientes fueron evaluadas basalmente y 6 semanas postintervención. La variable dependiente principal fue el dolor evaluado con la escala visual analógica y el cuestionario de dolor McGill. Como variable secundaria se evaluó el aspecto de la cicatriz según la escala de cicatrización de Vancouver y la Patient Scar Assessment Scale. Se analizó una muestra de 15 mujeres, 8 en el GC y 7 en el GI. Resultados: La edad media fue de 33,1 años (DE 4,1). En el análisis intragrupos se observó una disminución significativa en la valoración global del dolor según la escala visual analógica y el cuestionario de dolor McGill y en la dimensión PRI-Emocional. En el GI se observó también una disminución significativa en la dimensión PRI-Sensorial y PRI-Valorativa respecto a la situación basal. En ambos grupos se observó una mejoría significativa de la cicatrización de la lesión. En el análisis intergrupos se observó una mayor disminución del dolor pélvico en la subescala PRI-Sensorial del cuestionario de dolor McGill en el GI (−15,1 vs. −6; p=0,040). Conclusiones: Las infiltraciones de colágeno podrían mejorar el dolor y el aspecto de las cicatrices dolorosas.(AU)

Background and aims: Pelvic pain is a frequently consulted symptom in pelvic floor rehabilitation units. The aim of this study was to evaluate the efficacy of collagen infiltrations in pain and the appearance of scars from perineal tears, episiotomies and caesarean sections. Material and methods: Pilot randomized, controlled and single-blind clinical trial. Control group (CG) patients received conventional rehabilitation treatment. Additionally, those in the intervention group (IG) received 3-5 collagen infiltrations. The patients were evaluated at baseline and 6 weeks post-intervention. The main outcome was pain and it was evaluated with the visual analog scale and McGill Pain Questionnaire. As secondary outcomes, the appearance of the scar was evaluated by Vancouver Scar Scale and the Patient Scar Assessment Scale. A sample of 15 women was analyzed, 8 in the CG and 7 in the IG. Results: The mean age was 33.1 years (SD 4.1). The intragroup analysis showed a significant decrease of the visual analog scale punctuation and total McGill Pain Questionnaire score and the PRI-Emotional dimension of the McGill Pain Questionnaire. In the IG, a significant decrease was also observed in the PRI-Sensorial and PRI-Evaluative dimensions in comparison with baseline situation. In both groups, a significant improvement in the appearance of the scar was observed. In the intergroup analysis, a greater decrease in pain was observed in PRI-Sensorial subscale of the McGill Pain Questionnairein the IG (−15.1 vs. −6; P=.040). Conclusions: Collagen infiltrations may improve pain and the appearance of painful scars.(AU)

In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.

Complex roles of discoidin domain receptor tyrosine kinases in cancer

Discoidin domain receptors, DDR1 and DDR2 are members of the receptor tyrosine kinase (RTK) family that serves as a non-integrin collagen receptor and were initially identified as critical regulators of embryonic development and cellular homeostasis. In recent years, numerous studies have focused on the role of these receptors in disease development, in particular, cancer where they have been reported to augment ECM remodeling, invasion, drug resistance to facilitate tumor progression and metastasis. Interestingly, accumulating evidence also suggests that DDRs promote apoptosis and suppress tumor progression in various human cancers due to which their functions in cancer remain ill-defined and presents a case of an interesting therapeutic target. The present review has discussed the role of DDRs in tumorigenesis and the metastasis (AU)

Colágeno polivinilpirrolidona versus mitomicina C en trabeculectomía en pacientes con glaucoma primario de ángulo abierto. Seguimiento a 36 meses / Outcomes of trabeculectomy with polyvinylpyrrolidone collagen versus mitomycin in primary open angle glaucoma. 36-month follow-up

Propósito Describir y comparar los efectos de la aplicación intraoperatoria de colágeno polivinilpirrolidona (PVP) versus mitomicina C (MMC) en el patrón de cambio de la presión intraocular (PIO) y del número de medicamentos hipotensores utilizados en un seguimiento a 36 meses en pacientes con glaucoma primario de ángulo abierto (GPAA) operados de trabeculectomía. Métodos Estudio prospectivo, comparativo y aleatorizado. Veintiséis ojos de 26 pacientes con diagnóstico de GPAA, sin cirugías incisionales de glaucoma previas, fueron operados de trabeculectomía y aleatorizados a recibir PVP o MMC durante el procedimiento. Todos los pacientes cumplieron un seguimiento de 36 meses. Los resultados principales medidos fueron cambios en la PIO y el número de medicamentos hipotensores durante el seguimiento. Resultados El análisis multivariado reveló que la reducción de la PIO media del preoperatorio a los 36 meses de seguimiento fue de 7,62mmHg (3,05; 12,18) en el grupo de MMC y de 8,15mmHg (−0,64; 16,95) en el grupo de la PVP. La reducción media porcentual de la PIO fue del 37,09% (15,93; 58,17) en el grupo de MMC y del 36,08% (5,16; 67,20) en el grupo de la PVP. El cambio en el número de medicamentos del preoperatorio a los 36 meses de seguimiento fue de −0,92 medicamentos (-2,38; +1,54) para el grupo de MMC y de −1 medicamentos (−3,12, +1,12) para el grupo de la PVP. Ambos grupos tuvieron una disminución estadísticamente significativa de la PIO durante el seguimiento (p<0,001), pero no hubo una diferencia discernible entre los grupos (p=0,5975). El análisis de sensibilidad mostró que un modelo de tendencia lineal es adecuado para describir la reducción de la PIO durante el seguimiento. Ambos grupos tuvieron una reducción estadísticamente significativa de medicamentos del preoperatorio al final del seguimiento (p<0,05), tampoco hubo una diferencia discernible entre los grupos (p=0,2917)(AU)

Purpose Describe and compare the effects of intraoperative application of Polyvinylpyrrolidone Collagen (PVP) versus Mitomycin C (MMC) on the pattern of change in mean IOP reduction and mean number of medications over 36-months follow-up in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy. Methods Prospective, randomized, comparative study. Twenty-six eyes of 26 patients with POAG and no previous incisional glaucoma surgery underwent trabeculectomy and were randomized to PVP or MMC and completed a 36-month follow-up. Main outcome measures were IOP and number of glaucoma medications. Multivariate longitudinal analysis was performed by fitting a linear trend model adjusting for baseline response for the IOP outcome and a log-linear regression model with within-subject associations for the number of hypotensive medications outcome. Sensitivity analysis was performed to assess lower and higher order polynomial trends over time in IOP. Results The univariate analysis revealed that the mean IOP reduction from baseline to 36 months was 7.62mmHg (3.05; 12.18) in the MMC group and 8.15mmHg (−0.64; 16.95) in the PVP group. Mean percentage IOP reduction from baseline was 37.09% (15.93; 58.17) and 36.08% (5.16; 67.20) in the PVP group. Mean change in number of medications from baseline to 36 months was −0.92 medications (−3.38; +1.54) for the MMC group and −1 medication (−3.12; +1.12) for the PVP group. Both groups had a statistically significant decline in mean IOP over the follow-up period (p<0.001) but there was no discernible difference between the two exposure groups in the rate of change in IOP (p=0.5975). Sensitivity analysis showed that a linear trend model is adequate to describe the IOP reduction over the follow-up period. Both groups had a statistically significant change in the number of hypotensive medications used between baseline and month 36 (p<0.05) but there was no discernible difference between exposure groups (p=0.2917) (AU)

Epithelium-Off vs. transepithelial corneal collagen crosslinking in progressive keratoconus: 3 years of follow-up

Purpose: To compare the efficacy of epithelium-off corneal collagen crosslinking (CXL) with transepithelial CXL in patients with progressive keratoconus with a follow-up of 3 years, taking into account the patients’ age and the location of the corneal ectasia.MethodsIn this prospective study participated 64 eyes with progressive keratoconus were included in this long-term study, of which 31 eyes were treated by epithelium-off CXL and 33 by transepithelial CXL. All of the patients with a follow-up of 36 months were evaluated for visual variables (corrected distance visual acuity (CDVA), corneal aberrations, and corneal densitometry), structure variables (astigmatism, keratometry, corneal asphericity, maximum posterior elevation, corneal thickness, and corneal volume), and keratoconus index variables.ResultsAfter corneal CXL, CDVA improved significantly in both central and paracentral keratoconus, with greater improvement in the centrals (p = 0.001), asphericity at 6 mm improved in central keratoconus (p = 0.047). In the epi-off group, there was a significant improvement in coma-like (p = 0.038), higher-order aberrations (p = 0.036), asphericity at 8 mm (p = 0.049), asphericity at 10 mm (p = 0.049), and index of surface variance (p = 0.049).ConclusionAlthough both techniques halted and stabilized the progression of keratoconus, epithelium-off CXL was more effective. In addition, after the corneal CXL, there was a greater degree of regularization of the corneal surface and, therefore, a greater improvement in the CDVA with central keratoconus than with paracentral keratoconus. (AU)

The effectiveness of 7% table salt concentration test to increase collagen in the healing process of wound

Objective: Table salt (sodium chloride) is an ionic compound consisting of positive ions (cations) and negative ions (anions) to form neutral compounds that can provide a healing effect on wounds. This study's purpose of seeing and test the impact of soaking 7% sodium chloride concentration on people's salt toward the wound healing process. Method: This study was an experimental laboratory using the One-Way ANOVA test and the Mann Whitney test conducted in the animal enclosure of the Faculty of Pharmacy, Hasanuddin University, Makassar. The study was conducted from July to August 2019. Samples of 20 mice (Mus Musculus) female swiss webster strains were sliced on the abdominal skin then divided into two groups: the treatment group (n = 15) and the control group (n = 5). The wound area was observed from the first day to the seventh day to see the wound closure process. Results: The research shows that soaking 7% of table salt concentration can significantly accelerate the wound healing process compared to the control group, with a decrease in wound diameter on the 3rd day and completely heal on the 7th day. Conclusion: 7% concentration of table Salt Soaking can increase the effectiveness of wound healing. (AU)

The microanatomy of Bowman's layer in the cornea of the pig: Changes in collagen fibril architecture at the corneoscleral limbus

In most animals, Bowman's layer is a feature of the cornea of the eye, and lies between the sur-face epithelium and the stromal extracellular matrix that makes up the bulk of the cornea. It is comprised of a condensation of disorganised collagen fibrils. However, it has been conjectured that not all species possess Bowman’s layer, and pigs are a species that has classically been stated to lack this anatomical structure, although there is disagreement in the published literature. Here, we studied the porcine cornea using transmission and scanning electron microscopy (TEM and SEM) to ascertain whether Bowman’s layer existed. TEM identified a thin band of disorganised collagen fibrils between the epithelial basement membrane and corneal stroma. SEM images of the central and peripheral corneal surfaces, following removal of the corneal epithelium by cell maceration, revealed a disorganised meshwork of collagen fibrils, with a highly aligned annulus of collagen at the limbus. In between the peripheral cornea and limbus, a "transition zone" is observed where collagenfibrils start to align. Quantification of fibril alignment demonstrates a significant increase in collagen alignment from 0.08 ± 0.04 to 0.33 ± 0.07 (p < 0.001; n = 60; 0 = no alignment, 1 = full alignment) with increasing distance from the corneal centre. These data together lead us to conclude that the porcine cornea does include Bowman's layer, though it is thin (contributing roughly 0.2% of corneal thickness), and thus, reaffirms the porcine cornea's similarity to its human counterpart and usefulness as a model system

No disponible