Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1a/Notch1 signaling pathway

Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated.Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells (AU)

Hypoxia: molecular pathophysiological mechanisms in human diseases

Hypoxia, a low O2 tension, is a fundamental feature that occurs in physiological events as well as pathophysiological conditions, especially mentioned for its role in the mechanism of angiogenesis, glucose metabolism, and cell proliferation/survival. The hypoxic state through the activation of specific mechanisms is an aggravating circumstance commonly noticed in multiple sclerosis, cancer, heart disease, kidney disease, liver disease, lung disease, and in inflammatory bowel disease. On the other hand, hypoxia could play a key role in tissue regeneration and repair of damaged tissues, especially by acting on specific tissue stem cells, but their features may result as a disadvantage when it is concerned for neoplastic stem cells. Furthermore, hypoxia could also have a potential role in tissue engineering and regenerative medicine due to its capacity to improve the performance of biomaterials. The current review aims to highlight the hypoxic molecular mechanisms reported in different pathological conditions to provide an overview of hypoxia as a therapeutic agent in regenerative and molecular therapy. (AU)

Un viaje entre la hipoxia de la gran altitud y la hipoxia del enfermo crítico: ¿qué puede enseñarnos en la compresión y manejo de las enfermedades críticas? / A journey between high altitude hypoxia and critical patient hypoxia: What can it teach us about compression and the management of critical disease?

La hipoxia de la altitud (hipoxia hipobárica) no deja de ser una hipoxia celular similar a la que presentan los enfermos críticos. Estudiar a los alpinistas expuestos a la hipoxia extrema ofrece la ventaja de que es una población relativamente homogénea y sana, en contraste con la población heterogénea y generalmente menos saludable que suele observarse en las Unidades de Cuidados Críticos. El conocimiento de la fisiología y la enfermedad de la altitud abren caminos para comprender en qué medida afecta la hipoxia a los pacientes críticos. Los cambios comparables en la biogénesis mitocondrial entre ambos grupos pueden reflejar respuestas adaptativas similares y sugieren intervenciones terapéuticas basadas en la protección o estimulación de la biogénesis mitocondrial. El predominio del alelo homocigótico de inserción (II) de la enzima de conversión de la angiotensina está presente tanto en las ascensiones exitosas sin oxígeno por encima de los 8.000 m como en la supervivencia de algunas enfermedades de los enfermos críticos

High altitude sickness (hypobaric hypoxia) is a form of cellular hypoxia similar to that suffered by critically ill patients. The study of mountaineers exposed to extreme hypoxia offers the advantage of involving a relatively homogeneous and healthy population compared to those typically found in Intensive Care Units (ICUs), which are heterogeneous and generally less healthy. Knowledge of altitude physiology and pathology allows us to understanding how hypoxia affects critical patients. Comparable changes in mitochondrial biogenesis between both groups may reflect similar adaptive responses and suggest therapeutic interventions based on the protection or stimulation of such mitochondrial biogenesis. Predominance of the homozygous insertion (II) allele of the angiotensin-converting enzyme gene is present in both individuals who perform successful ascensions without oxygen above 8000 m and in critical patients who overcome certain disease conditions

Papel del internista en un programa de optimización de uso transfusional / The role of the internist in the patient blood management program

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Protective role of downregulated MLK3 in myocardial adaptation to chronic hypoxia

A series of protective responses could be evoked to achieve compensatory adaptation once cardiomyocytes are subjected to chronic hypoxia. MLK3/JNK/c-jun signaling pathway was previously demonstrated to be involved in this process. In the present study, we aim to further examine the performance of MLK3 in hypoxic H9C2 cells and potential mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected. H9C2 cells were cultured in hypoxic conditions for various durations. MLK3 was silenced by transfection of shRNA to evaluate its role in cell viability. We found expression of MLK3 protein was lower in patients with cyanotic CHD. In hypoxic H9C2 cells, its expression was gradually decreased in a time-dependent manner. However, there was no significant difference about expression of MLK3 mRNA. According to the results of MTT, LDH, and TUNEL, faster cell growth curve, lower death rate, and less apoptotic cells could be observed in MLK-shRNA group compared with scramble-shRNA group. Silencing of MLK3 significantly reduced expression of cleaved caspase-3, cleaved PARP, Bad, and Bax, together with increased expression of Bcl-2 and ration of Bcl-2/Bax. Both ratio of phospho-JNK/total JNK and ratio of phospho-c-jun/total c-jun were significantly decreased once MLK3 was silenced. At various reoxygenation time, MLK3 shRNA could significantly promote cell survival and decrease cell death according to MTT and LDH. Our results suggested that chronic hypoxia could reduce MLK3 expression in a posttranscriptional regulatory manner. Downregulation of MLK3 protects H9C2 cells from hypoxia-induced apoptosis and H/R injury via blocking the activation of JNK and c-jun

Paraganglioma asociado a cardiopatía congénita cianótica: papel de la hipoxia tisular / Paraganglioma and cyanotic congenital heart disease: The role of tisular hipoxia

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Cambios morfológicos y morfométricos en los capilares del nervio óptico de rata en un modelo experimental de glaucoma / Morphological and morphometric changes in rat optic nerve microvessels in a glaucoma experimental model

OBJETIVO: Estudiar los cambios morfológicos y morfométricos producidos en los capilares de la cabeza del nervio óptico (NO) y de su porción inicial, después de la elevación experimental de la presión intraocular (PIO). MATERIAL Y MÉTODOS: Se utilizaron ratas Wistar que fueron sometidas a cauterización de 3 venas epiesclerales, con el resultado inmediato de elevación de la PIO, manteniéndose esta durante 3 meses. Se realizaron secciones sagitales del globo ocular y se aplicaron técnicas inmunohistoquímicas, mediante un anticuerpo para GLUT-1. Se procedió al recuento de los capilares GLUT-1 positivo y se midieron área, perímetro y diámetro medio. RESULTADOS: El examen microscópico de las secciones del NO de las ratas controles demostró una menor densidad de capilares y un mayor calibre de los mismos en la región prelaminar, respecto a las demás regiones del NO (p < 0,05). Cuando se compararon los grupos control y experimental se observó una disminución en la densidad de capilares (excepto en la región prelaminar) y un menor tamaño de los mismos en todas las zonas del NO analizadas, menos evidente en la porción inicial (p < 0,05). CONCLUSIONES: El aumento de la PIO se relaciona con cambios cualitativos y cuantitativos de los capilares de las regiones laminar y poslaminar de la cabeza del NO, y parecen recuperarse hacia parámetros compatibles con la normalidad en la porción inicial del NO, donde el colapso vascular es menos evidente. Estos hallazgos podrían explicar la reducción significativa del flujo sanguíneo ocular observada en pacientes con glaucoma primario de ángulo abierto

AIM: To study the morphological and morphometric changes produced in the capillaries of the optic nerve (ON) head and initial portion after the experimental increase in intraocular pressure (IOP). MATERIAL AND METHODS: Wistar rats underwent cauterization of three episcleral veins, which produced an immediate increase in the IOP, and was maintained for 3 months. Sagittal sections of the eyeball were studied with immunohistochemical techniques, using a primary antibody to GLUT-1. The GLUT-1 positive capillaries were counted, and measurements were made of the area, perimeter and mean diameter. RESULTS: Microscopic examination of sections of the ON of control rats revealed a lower density and larger caliber of capillaries in the prelaminar region as compared with the other regions of the ON (P<.05). Comparison between the control and the experimental groups showed a reduction in capillary density (except in the prelaminar region) and a smaller size in all the areas of the ON studied, but less evident in the initial portion (P<.05). CONCLUSIONS: The increase in IOP was associated with significant qualitative and quantitative changes in the capillaries of the laminar and poslaminar regions of the ON head. These changes appear to return towards parameters compatible with normality in the initial portion of the ON, an area where the vascular collapse was less evident. These findings might explain the significant reduction in ocular blood flow seen in patients with primary open-angle glaucoma

Conceptos generales y bases científicas de la oxigenoterapia domiciliaria / No disponible

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Oxigenoterapia domiciliaria durante el sueño autores / No disponible

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Síndrome de distrés mitocondrial y de la microcirculación en el paciente crítico. Implicaciones terapéuticas / Mitochondrial and microcirculatory distress syndrome in the critical patient. Therapeutic implications

Síndrome de distrés mitocondrial y de la microcirculación (SDMM) es una entidad que puede aparecer en el curso del síndrome de respuesta inflamatoria sistémica (SRIS), que se caracteriza por una hipoxia tisular citopática no corregible con la optimización del transporte de oxígeno, asociada a un defecto adquirido para la utilización de oxígeno y producción de energía en la mitocondria y que da lugar a disfunción múltiple de órganos (DMO).Abordamos la etiopatogenia del SDMM, los nuevos métodos para su diagnóstico y los recientes enfoques terapéuticos adaptados a cada una de las 3 fases de su evolución. En la fase inicial lo que se persigue es la prevención y reversión precoz de la disfunción mitocondrial. Una vez esta ya está establecida, el objetivo es restaurar el flujo de la cadena de electrones, la respiración mitocondrial y evitar el colapso energético celular. En la tercera etapa, de resolución, el tratamiento debe ir dirigido a estimular la biogénesis mitocondrial y la reparación o sustitución de las mitocondrias dañadas (AU)

Mitochondrial and microcirculatory distress syndrome (MMDS) can occur during systemic inflammatory response syndrome (SIRS), and is characterized by cytopathic tissue hypoxia uncorrected by oxygen transport optimization, and associated with an acquired defect in the use of oxygen and energy production in mitochondria, leading to multiple organ dysfunction (MOD).We examine the pathogenesis of MMDS, new diagnostic methods, and recent therapeutic approaches adapted to each of the three phases in the evolution of the syndrome. In the initial phase, the aim is prevention and early reversal of mitochondrial dysfunction. Once the latter is established, the aim is to restore flow of the electron chain, mitochondrial respiration, and to avoid cellular energy collapse. Finally, in the third (resolution) stage, treatment should focus on stimulating mitochondrial biogenesis and the repair or replacement of damaged mitochondria (AU)

Eficacia de la detección percutánea de oxígeno como guía terapéutico-quirúrgica en lesionados medulares con úlceras por presión crónicas: estudio preliminar / Eficacy of percutaneous oxygen detection as therapeutic-surgical guide in spinal cord injury patients with chronic pressure ulcers: preliminary report

En el presente estudio clínico realizamos detección transcutánea de oxígeno (TcpO2) en 11 pacientes consecutivos lesionados medulares parapléjicos crónicos (de más de 1 año de evolución) con úlceras por presión (upp) crónicas de grado IV (de más de 6 meses de evolución). En todos analizamos los valores de la TcpO2 tanto en el momento preoperatorio como postoperatorio, llevando a cabo las siguientes comprobaciones. En la posición 1 preoperatorio (P1-pre: a 1 cm del borde de la upp) los valores obtenidos fueron de 27,28±13,83 mm Hg, mientras que en P1 postoperatorio fueron de 34,96±19,06 (p < 0.05). El valor medio del electrodo de referencia (no1) en el momento preoperatorio (51,63±12,53mm Hg) fue estadísticamente significativo (p < 0.05) al compararlo con el valor obtenido con el electrodo no1 (38,60±14,63 mm Hg) en el postoperatorio. El valor medio del electrodo de referencia (no1) en el momento del preoperatorio (50,07±13,54 mm Hg) es estadísticamente significativo (p < 0.05) al compararlo con los valores medios obtenidos de TcpO2 de las posiciones (P1+P2+P3) de los electrodos no2 (29,17±15,03 mm Hg), no3 (34,51±13,15 mm Hg) y no4 (30,37±17,81 mm Hg) analizados en el preoperatorio. Demostramos con estos hallazgos los niveles hipoxémicos a 1 cm del borde de una upp grado IV y su evolución postoperatoria. De esta forma, la técnica de detección transcutánea de oxígeno puede considerarse una guía terapéutica en la detección y en la monitorización del tratamiento de las upp, con la posibilidad de establecer intervenciones terapéuticas para poder mejorar los niveles de oxígeno detectados en las mismas (AU)

In this clinical study the detection of transcutaneous oxygen has been performed (TcpO2) to 11 consecutive patients with spinal cord injury chronic paraplegics (more than 1 year of evolution) with chronic pressure ulcers grade IV (more than 6 months). In all patients were analyzed preoperative and postoperative TcpO2 values, with the following results. In the preoperative position 1 (P1-pre: to 1 cm of the ulcer edge) values obtained are of 27.28 ± 13.83 mm Hg, while in P1 postoperative were 34.96 ± 19.06 (p < 0.05). The average value of the reference electrode (no 1) preoperative (51.63 ± 12.53 mm Hg) is statistically significant (p < 0.05) when compared with the value obtained with the electrode no1 (38.60 ± 14, 63 mmHg) in the postoperative state. The average value of the reference electrode (no 1) preoperative (50.07 ± 13.54 mm Hg) is statistically significant (p < 0.05) when compared with the average values of the positions (P1, P2, P3) obtained of TcPO2 electrode no 2 (29.17 ± 15.03 mm Hg), no 3 (34.51 ± 13.15 mm Hg) and no 4 (30.37 ± 17.81 mm Hg) analyzed preoperatively. With these findings, we demonstrate hypoxemic levels to 1 cm of chronic pressure ulcers edge grade IV and postoperative progress. Thus, the technique of transcutaneous oxygen detection can be considered as a therapeutic guide in the detection and monitoring of pressure ulcers treatment with the possibility of establish therapeutic interventions to improve the oxygen levels detected in them (AU)

La hipoxia estimula la expresión del receptor LRP1 a través del factor de transcripción HIF-1α en células musculares lisas de pared vascular humana / Hypoxia stimulates LRP1 expression through HIF-1α transcription factor in human vascular wall smooth muscle cells

Introducción La hipoxia se considera un factor clave en la progresión de las lesiones ateroscleróticas. El low density lipoprotein receptor-related protein-1 (LRP1) juega un papel fundamental en la vasculatura. El propósito de este estudio fue investigar el efecto de la hipoxia en la expresión y la función del LRP1 en células musculares lisas vasculares (CMLV) y el papel del factor de transcripción inducible por la hipoxia 1 alfa (..) (AU)

Objective Hypoxia is considered a key factor in the progression of atherosclerotic lesions. Low density lipoprotein receptor-related protein 1 (LRP1) plays a pivotal role in the vasculature. The aims of this study were to investigate the effect of hypoxia on LRP1 expression and function in vascular smooth muscle cells (VSMC) and the role of hypoxia-inducible factor alpha (..) (AU)

Clinical study on the recombinant human endostatin regarding improving the blood perfusion and hypoxia of non-small-cell lung cancer

OBJECTIVE: To observe the dynamic changes of blood perfusion and hypoxic status with CT perfusion imaging and hypoxia imaging in patients of non-small-cell lung cancer (NSCLC) who were treated with recombinant human endostatin (RHES). METHODS: Fifteen previously untreated patients with histologically or cytologically confirmed NSCLC were enrolled. They were randomly divided into research group (n=10) and negative control group (n=5). The patients of the research group continuously used RHES for ten days, and simultaneously had CT perfusion imaging and hypoxia imaging performed on days 1, 5 and 10, respectively. The remaining 5(control) only had CT perfusion imaging and hypoxia imaging, without using RHES, on days 1, 5 and 10, respectively. According to the above results, we could obtain a "time window" during which RHES improves blood perfusion and hypoxia of lung cancer. RESULTS: In the research group, after using RHES, capillary permeability surface (PS) and tumour to normal tissue (T/N) decreased at first, and then increased. Their lowest points occurred on about the fifth day with statistical significance compared with the first day (T/N, p=0.00; PS, p<0.01). Blood flow (BF) was first increased and then decreased. Its highest point occurred on about the fifth day with statistical significance compared with the first and tenth day (all p<0.01). The PS, BF and T/N peaked on the fifth day in the research group with statistical significance compared with the negative control group as well (all p<0.01). The above results suggested that RHES's "time window" was within about one week after administration. ¡CONCLUSION: RHES's "time window" is within about one week after administration, which provides an important experimental basis for combining RHES with radiotherapy in human tumours (AU)

Preliminary clinical study of weekly recombinant human endostatin as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of NSCLCP

OBJECTIVE: To investigate the clinical effects and adverse effects of weekly recombinant human endostatin (RHES) as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of non-small-cell lung cancer (NSCLC). METHODS: Fifty hypoxia-positive cases of pathology-diagnosed NSCLC (stage I-III) were randomly divided into a RHES+radiotherapy group (25 cases) and a radiotherapy alone group (25 cases). Intensity-modulated radiotherapy (IMRT) with a total dose of 60 Gy/30F/6W was adopted in the two groups. Target area included primary foci and metastatic lymph nodes. In the RHES+radiotherapy group, RHES (15 mg/day) was intravenously given during the first week. The therapeutic effects and adverse reactions were evaluated after treatment. RESULTS: In the RHES+radiotherapy and radiotherapy alone groups, the total effective rates (CR+PR) were 80% and 44% (χ(2)=6.87, p=0.009), respectively. The one-year and two-year local control rates were (78.9±8.4)% and (68.1±7.8)% (p=0.027), and (63.6±7.2)% and (43.4±5.7)% (p=0.022), respectively. The median progression-free survival was (21.1±0.97) and (16.5±0.95) months, respectively. The one-year and two-year overall survival rates were (83.3±7.2)% and (76.6±9.3)% (p=0.247), and (46.3±2.4)% and (37.6±9.1)% (p=0.218), respectively. CONCLUSION: RHES combined with radiotherapy within the first week has better short-term therapeutic effects and local control rate, and no severe adverse reactions in treatment of NSCLC. However, it failed to significantly improve the one-year and two-year overall survival rates (AU)

Objetivos de la reanimación hemodinámica / Objectives of hemodynamic resuscitation

La insuficiencia cardiovascular o shock, de cualquier etiología, se caracteriza por la inadecuada perfusión de los tejidos del organismo, produciendo una situación de desequilibrio entre el aporte y la demanda de oxígeno. La disminución de la disponibilidad de oxígeno en el área celular se traduce en un aumento del metabolismo anaerobio, con producción de lactato e hidrogeniones, derivando en la acidosis láctica. El grado de hiperlactatemia y acidosis metabólica va a correlacionarse directamente con el desarrollo de fracaso orgánico y mal pronóstico del individuo.La llegada de oxígeno a los tejidos depende fundamentalmente de una presión de perfusión del tejido suficiente y de un transporte de oxígeno adecuado. La adecuación de estos dos parámetros fisiológicos va a posibilitar la restauración del equilibrio entre aporte y demanda celular de oxígeno, revirtiendo el proceso de anaerobiosis. La monitorización de variables como el lactato y las saturaciones venosas de oxígeno (central o mixta) durante la fase aguda del shock serán útiles en la determinación de persistencia o resolución de la hipoxia tisular. En los últimos años, han aparecido nuevas tecnologías capaces de evaluar la perfusión local y la microcirculación, como la tonometría gástrica, la espectroscopia en el límite de la luz infrarroja y la videomicroscopia. Aunque la monitorización de parámetros de carácter regional ha demostrado su valor pronóstico, no se dispone de evidencia suficiente que le otorgue utilidad en la guía del proceso de reanimación. En conclusión, a la espera de disponer de parámetros capaces de proporcionarnos información útil de perfusión local, la reanimación hemodinámica sigue basada en la (..)(AU)

Cardiovascular failure or shock, of any etiology, is characterized by ineffective perfusion of body tissues, inducing derangements in the balance between oxygen delivery and consumption. Impairment in oxygen availability on the cellular level causes a shift to anaerobic metabolism, with an increase in lactate and hydrogen ion production that leads to lactic acidosis. The degree of hyperlactatemia and metabolic acidosis will be directly correlated tothe development of organ failure and poor outcome of the individuals. The amount of oxygen available at the tissues will depend fundamentally on an adequate level of perfusion pressure and oxygen delivery. The optimization of these two physiologic parameters can re-establish the balance between oxygen delivery and consumption on the cellular level, thus, restoring the metabolism to its aerobic paths. Monitoring variables such as lactate and oxygen venous saturations (either central or mixed) during the initial resuscitation of shock will be helpful to determine whether tissue hypoxia is still present or not. Recently, some new technologies have been developed in order to evaluate local perfusion and microcirculation, such as gastric tonometry, near-infrared spectroscopy and video microscopy. Although monitoring these regional parameters has demonstrated its prognostic value, there is a lack of evidence regarding to its usefulness during the resuscitation process. In conclusion, hemodynamic resuscitation is still based on the rapid achievement of adequate levels of perfusion pressure, and then on the modification of oxygen delivery variables, in order to restore physiologic values of ScvO2/SvO2 and resolve lactic acidosis and/or hyperlactatemia (AU)

Empleo de la oxigenoterapia hiperbárica en Urología / Hypebaric oxygen treatment in urology

OBJETIVO: La oxigenoterapia hiperbárica (OHB) se ha empleado de forma existosa en numerosas patologías que derivan de la hipoxia tisular gracias al aporte extra de oxígeno que permite a los tejidos.En este trabajo se realiza una revisión exhaustiva acerca de toda la literatura existente en 2010 en la que se emplea OHB en patología urológica.MÉTODOS: Realizamos una búsqueda en Medline introduciendo los términos “hyperbaric oxygen”, “radic cistitis”, “interstitial cistitys”, “ hemorraghic cistitys”, “urological/pelvic fistula” y “Fournier´s gangrene”.Las búsquedas se centraron en estudios en humanos únicamente publicados en cualquier idioma.RESULTADOS: 56 trabajos publicados, 1 ensayo clínico controlado aleatorizado (ECA), 7 revisiones (review) y 48 series de casos (SC) de los que tan solo uno fué prospectivo en los que se exponen a un total de 695 pacientes. Sólo en un estudio se emplearon mediciones de oxígeno tisular para definir la hipoxia. El número de las sesiones de terapia de oxígeno hiperbárico varió desde 4 hasta 44 sesiones. (media 19,2 sesiones/paciente)CONCLUSIONES: La evidencia que se extrae de la mayoría de trabajos consultados procede de series de casos, de modo que es baja, sin embrago, en la mayoría de estudios los resultados en cuanto al manejo de los pacientes es bueno o muy bueno así que parece que la OHB puede ser de gran utilidad en enfermedades urológicas que deriven de hipoxia tisular(AU)

OBJECTIVES: Hyperbaric oxygen therapy (HBO) has been successfully used in several disorders derived from tissue hypoxia, due to the extra oxygen supply to the tissues it enables.In this manuscript we performed a systematic review including all the existing data published until 2010 about HBO in urologic disorders.METHODS: We performed a Medline search using the terms “hyperbaric oxygen”, “radical cystitis”, “interstitial cystitis”, “hemorrhagic cystitis”, “urological/pelvic fistula” and “Fournier´s gangrene”. The search was restricted to human clinical trials published in any language. RESULTS: We found 56 papers: 1 randomized controlled trial, 7 reviews and 48 case reports; only one of them was a prospective study. A total of 695 patients were included. Just one study used tissue oxygen measurement to define hypoxia. The number of hyperbaric oxygen therapy sessions ranged from 4 to 44 (mean 19.2 sessions/patient).CONCLUSIONS: The level of evidence from most reviewed papers is low because most of them are case series. Nevertheless, results of most of those studies regarding patient management are good or very good. So it seems that HBO can be very useful in urological diseases related to tissue hypoxia(AU)

Erythropoietin ameliorates the reduced migration of human fibroblasts during in vitro hypoxia

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Erythropoietin promotes the formation of granulation tissue when administered to soft tissue wounds and it was shown to be most effective under tissue hypoxia. However, the action of erythropoietin on the cellular level is not well understood. In order to get a better insight into these processes, an in vitro wound healing assay was applied. Two main players of soft tissue healing—fibroblasts and microvascular endothelial cells—were used as mono- and co-cultures, subsequently inflicting in vitro wounds. Cell migration, proliferation, the differentiation of fibroblasts to myofibroblasts, and the release of vascular endothelial cell growth factor A and angiogenin were quantified in response to hypoxia and erythropoietin (5 IU/ml). Erythropoietin supplementation did neither affect proliferation nor migration of endothelial cells and fibroblasts under normoxia. Under hypoxia, the reduced fibroblast migration was ameliorated by erythropoietin. This effect coincided with an attenuated release of vascular endothelial growth factor A, whereas angiogenin release was unaffected by erythropoietin. The in vitro model applied in this study may represent an adequate approximation to certain aspects of the in vivo status of soft tissue regeneration and the results might serve to interpret the in vivo efficiency of erythropoietin at the cellular level: Erythropoietin has different impacts on the cells in normoxia and hypoxia. Its positive influence on fibroblast migration during hypoxia seems to support the strategies of applying erythropoietin in those chronic wounds, which exhibit fibroblastic dysfunction although good vascularisation is present (AU)