Adipose tissue-derived mesenchymal stromal cells as part of therapy for chronic graft-versus-host disease: A phase I/II study.

BACKGROUND AIMS: Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD. METHODS: Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 106/kg (group A, n = 9) or 3 × 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy. RESULTS: Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells. DISCUSSION: AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.

[8-oxo-7,8-dihydro-2'-deoxyguanosine as a marker of DNA oxidative stress in individuals with combined familiar hyperlipidemia]. / Estudio de los valores de 8-oxo-7,8-dihidro-2'-desoxiguanosina como marcador de estrés oxidativo del ADN en pacientes con hiperlipemia familiar combinada.

BACKGROUND AND OBJECTIVE: To compare 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) value as an indicator of oxidative stress situation between healthy and familial combined hyperlipidemic (FCH) subjects as a mixed dislipidemia with insulin resistance model and early coronary heart disease, and to study its relationship with clinical-biologic parameters of insulin resistance. SUBJECTS AND METHOD: 40 non-related FCH patients (15 women) and 20 normolipidemic and nondiabetic healthy subjects (8 women) were studied. Clinical, anthropometric and biochemical parameters (lipidic profile, glucemia, insulinemia and 8-oxo-dG) were measured in fasting state in all. RESULTS: Both groups had similar age, body mass index blood pressure and waist perimeter values. Insulin and 8-oxo-dG values were significantly higher in FHC subjects. These differences were maintained after correcting by waist perimeter. 8-oxo-dG correlated positively with insulin and trygliceride; and negatively with high density lipoprotein cholesterol in FCH subjects. CONCLUSIONS: Insulin values are independently correlated with oxidative stress degree measured as 8-oxo-dG.

Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative stress in human hypertension.

Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of beta-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress.

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a reliable oxidative stress marker in hypertension.

UNLABELLED: The potential use of oxidative stress products as disease markers and progression is an important aspect of biomedical research. In the present study, the quantification of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) concentration has been used to express the oxidation status of hypertensive subjects. 8-oxo-dG has been simultaneously isolated and assayed in nuclear (nDNA) and mitochondrial DNA (mtDNA). In addition, oxidative stress of mononuclear cells has been estimated by means of GSH and GSSG levels and GSSG/GSH ratio in hypertensive subjects before and after antihypertensive treatment. It is shown that oxidative stress decreases significantly in hypertensive patients after treatment the effect being accompanied by reduction of their blood pressure. A significant correlation is observed comparing the yield of urine 8-oxo-dG and that isolated from mitochondria DNA. Moreover, urinary excretion of 8-oxo-dG also correlates with the GSSG/GSH ratio of cells. CONCLUSION: urine 8-oxo-dG assay is a good marker for monitoring oxidative stress changes in hypertensives.

Impairment of antioxidant enzymes, lipid peroxidation and 8-oxo-2'-deoxyguanosine in advanced epithelial ovarian carcinoma of a Spanish community.

In the present study, we describe the changes of antioxidant enzyme activities and other oxidative stress-related parameters in a mediterranean cohort of women affected with epithelial ovarian carcinoma (EOC). For that purpose, the most representative enzymatic activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the oxidized/reduced glutathione (GSSG/GSH) ratio have been analyzed in tumor tissue biopsies and compared with the normal tissue of the same patient. As oxidation products, the levels of malondialdehyde (MDA) as an indication of lipid peroxidation, and the DNA damaged base 8-oxo-2'-deoxyguanosine (8-oxo-dG) have been also measured. Advanced EOC show reduced levels of SOD and CAT, while that of GPx is increased when compared with non-neoplastic tissue. The levels of GSH are increased giving as a result a reduction of the oxidative stress marker GSSG/GSH ratio comparing normal ovarian tissue with tumor tissue. In addition, the oxidation products MDA and 8-oxo-dG are significantly increased in tumor tissue, suggesting a shift of oxidative metabolisms towards a pro-oxidation state and potential gene instability in malignant ovary cells. The possible implication of the redox changes and DNA damage in tumor development is discussed.

Los ''escotomas'' del campo médico que limitan su papel en la salud sexual y reproductiva (SSR) de los adolescentes: ideas para superarlos / ''Scotomas'' of the medical field that limit its role in sexual and reproductive health of adolescents. Ideas to overcome them

Este artículo revisa el papel del campo médico en la salud sexual y reproductiva (SSR) de los adolescentes; a partir de una perspectiva histórica de la configuración de dos especializaciones médicas para intervenirla -la Medicina de Adolescentes y la Ginecología Infanto-Juvenil- identifica aspectos que actúan como ''escotomas'' limitantes de su capacidad resolutiva en la problemática de la SSR. Rescata aportes teóricos de corrientes crítico-sociales, resaltando algunos del movimiento latinoamericano de salud colectiva y de las teorías feministas, fundamentales para superarlos tales como la determinación social y del género en la salud y enfoques y prácticas médicas institucionalizados en Latinoamérica, que yacen detrás de políticas que perpetúan las inequidades en salud en este campo de la SSR. Por último, revela un novedoso concepto: el de ''ciudadanía sexual'' útil para integrar dichos aportes teóricos y metodológicos en un análisis relacional con sexualidades, subjetividades e identidades. La incorporación de estos desarrollos teóricos en programas de formación médica daría un profundo giro al papel del campo médico interpelado por el nuevo marco conceptual y ético del sistema de Naciones Unidas, acordado en las conferencias de El Cairo (1994) y Beijing (1995), instando a los estados a ofrecer políticas con garantías de los derechos sexuales y reproductivos (DSR).

This paper reviews the role of the medical field in adolescent sexual and reproductive health (ASRH). A brief historical account of the emergence of two specialties -Adolescent and Young Adult Medicine and Youth and Adolescent Gynecology- shows a predominance of the medical views and practices that act as ''scotomas'' limiting the role on ASRH promotion. It offers a conceptual framework built from critical social sciences, standing out the innovative contributions made by the Latin American collective health and feminism movements to overcome such ''scotomas'' by offering a better comprehension of key points involved in ASRH. Among them: the social and gender determination on health, the hegemonic medical institutional discourses and practices that perpetuate health inequities in relation to sexualities, subjectivities and identities of patients. The concept of ''sexual citizenship'' is presented as a useful analytical and methodological tool to integrate all these key points. Their incorporation into medical training programs would produce a deep turn in medicine granting the fulfillment of goals set out in the international conferences of Cairo and Beijing that urged governments to carry out actions to attend adolescent's needs and demands by granting their sexual and reproductive rights (SRR), thus providing the enhanced role that medicine must play in ASRH.

''Scotomes'' or ''blind spots'' in the medical field that limit its role in adolescent sexual and reproductive health (ASRH): ideas about how to eliminate them / Los "escotomas" del campo médico que limitan su papel en la salud sexual y reproductiva (SSR) de los adolescentes: ideas para superarlos

This article reviews the medical field's role in adolescent sexual and reproductive health (ASRH) from the historical perspectives of two influential medical specialties: adolescent and young adult medicine and pediatric and adolescent gynecology. The article identifies aspects that act as blind spots, limiting the medical field's capacity to respond to the challenges of ASRH. The article reviews the theoretical contributions of the critical social sciences, highlighting some of Latin America's collective health movements and feminist theories, as well as the hegemonic medical institutional discourses and practices that perpetuate health inequities in relation to patients' sexualities, subjectivities and identities. Finally, this paper presents a new concept: that of ''sexual citizenship,'' a useful concept that integrates these theoretical and methodological contributions into a relational analysis that includes sexualities, subjectivities and identities. The incorporation of these theoretical developments into medical training programs would generate a radical change in the role of the medical field that has been challenged by the new conceptual and ethical framework of the UN system, as confirmed at the conferences in Cairo (1994) and Beijing (1995). These conferences urged states to offer policies that guarantee sexual and reproductive rights (SRR).

Este artículo revisa el papel del campo médico en la salud sexual y reproductiva (SSR) de los adolescentes; a partir de una perspectiva histórica de la configuración de dos especializaciones médicas para intervenirla ­la Medicina de Adolescentes y la Ginecología Infanto-Juvenilidentifica aspectos que actúan como "escotomas" limitantes de su capacidad resolutiva en la problemática de la SSR. Rescata aportes teóricos de corrientes crítico-sociales, resaltando algunos del movimiento latinoamericano de salud colectiva y de las teorías feministas, fundamentales para superarlos tales como la determinación social y del género en la salud y enfoques y prácticas médicas institucionalizados en Latinoamérica, que yacen detrás de políticas que perpetúan las inequidades en salud en este campo de la SSR. Por último, revela un novedoso concepto: el de "ciudadanía sexual" útil para integrar dichos aportes teóricos y metodológicos en un análisis relacional con sexualidades, subjetividades e identidades. La incorporación de estos desarrollos teóricos en programas de formación médica daría un profundo giro al papel del campo médico interpelado por el nuevo marco conceptual y ético del sistema de Naciones Unidas, acordado en las conferencias de El Cairo (1994) y Beijing (1995), instando a los estados a ofrecer políticas con garantías de los derechos sexuales y reproductivos (DSR).

Insulin resistance and oxidative stress in familial combined hyperlipidemia.

Oxidative stress is associated with atherosclerosis. Familial combined hyperlipidemia (FCH) is considered as a human model of primary dyslipidemia and atherosclerosis frequently associated with insulin resistance (IR), but there are few data on its possible relation to oxidative stress. The objective of this study was to evaluate oxidative stress status using different markers in subjects with FCH assessing its possible correlation with anthropometric parameters and IR. This was a cross-sectional study. A cohort of 40 FCH patients (20 with IR (HOMA>or=3.2) and 20 without IR (HOMA<3.2)), and 20 healthy volunteers were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose and insulin levels in plasma, HOMA, and representative indicators of oxidative stress such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSSG/GSH ratio in mononuclear cells. All parameters were determined at basal conditions with standard methodology in the three groups. All FCH subjects showed an increased status of oxidative stress compared to the control group. When the impact of IR was investigated, significant differences between groups were observed in terms of increased levels of 8-oxo-dG, GSSG and GSSG/GSH ratio in FCH subjects with IR indicating higher levels of oxidative stress in these patients. Correlation studies showed that 8-oxo-dG and GSSG/GSH ratio are independently related to IR with odds ratio of 3.5 and 7.4, respectively. We conclude that FCH is related to oxidative stress, especially in the presence of IR.