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Hospital Universitario Reina Sofia

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Muntane J.,University of Cordoba, Spain | Muntane J.,Hospital Universitario Reina Sofia
Chemical Research in Toxicology | Year: 2011

Cancer is the second-leading cause of death in the U.S. behind heart disease and over stroke. The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The inhibition of cell death pathways is one of these tumor characteristics which also include sustained proliferative signaling, evading growth suppressor signaling, replicative immortality, angiogenesis, and promotion of invasion and metastasis. Cell death is mediated through death receptor (DR) stimulation initiated by specific ligands that transmit signaling to the cell death machinery or through the participation of mitochondria. Cell death involving DR is mediated by the superfamily of tumor necrosis factor receptor (TNF-R) which includes TNF-R type I, CD95, DR3, TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 (TRAIL-R1) and -2 (TRAIL-R2), DR6, ectodysplasin A (EDA) receptor (EDAR), and the nerve growth factor (NGF) receptor (NGFR). The expression of these receptors in healthy and tumor cells induces treatment side effects that limit the systemic administration of cell death-inducing therapies. The present review is focused on the different therapeutic strategies such as targeted antibodies or small molecules addressed to selective stimulated DR-mediated apoptosis or reduce cell proliferation in cancer cells. © 2011 American Chemical Society.

Sanchez-Garrido M.A.,University of Cordoba, Spain | Sanchez-Garrido M.A.,Hospital Universitario Reina Sofia | Tena-Sempere M.,University of Cordoba, Spain | Tena-Sempere M.,Hospital Universitario Reina Sofia
Hormones and Behavior | Year: 2013

This article is part of a Special Issue "Puberty and Adolescence".Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin and putatively related pathways in the concerted control of puberty by energy balance and metabolism. © 2013 Elsevier Inc..

Objective: To evaluate the effectiveness of acupuncture and traditional Chinese dietary therapy (TCDT) as single therapies in reducing pain and improving quality of life in patients with fibromyalgia (FM) versus combined treatment with acupuncture and TCDT in the province of Cordoba. Design: A controlled randomized trial was performed to evaluate the effectiveness of acupuncture combined with TCDT compared with acupuncture alone or TCDT alone. The combined treatment was performed in two modalities: simultaneously and sequentially. Setting: Reina Sofía University Hospital, Cordoba, Spain. Participants: A total of 120 patients with FM clinically confirmed in the rheumatology service, divided in four groups. Interventions: Acupuncture (a cycle of 10 sessions) and TCDT, applied alone, simultaneously and sequentially. Main outcome measures: Total pain scale and each of its components, visual analog scale and a questionnaire on the impact of FM at 3, 4, 5, 6 months after the start of the interventions. Results: Treatment with TCDT alone did not improve FM symptoms. The combination of TCDT with acupuncture produced significant improvements (p < 0.05). At 6 months, the best results were achieved in the acupuncture group. Conclusions: The application of TCDT together with acupuncture is an effective measure to improve the therapeutic approach, although acupuncture produced the greatest improvements.

Toledano F.J.,Hospital Universitario Reina Sofia
The American journal of emergency medicine | Year: 2012

Lung cancer is one of the most common neoplasms associated with cardiac metastasis, and the pericardium is often affected. However, isolated myocardial involvement in these patients is very uncommon. Most tumor invasions into the heart are nonspecific and clinically silent. Myocardial metastasis rarely mimics an acute myocardial infarction. We report a case of a 59-year-old man with a metastatic lung cancer into the myocardium mimicking an acute myocardial infarction.

Cunningham J.,University College London | Locatelli F.,Dialysis and Renal Transplant | Rodriguez M.,Hospital Universitario Reina Sofia
Clinical Journal of the American Society of Nephrology | Year: 2011

Secondary hyperparathyroidism (SHPT) is a challenge frequently encountered in the management of patients with chronic kidney disease (CKD). Downregulation of the parathyroid vitamin D and calcium-sensing receptors represent critical steps that lead to abnormalities in mineral metabolism: high phosphate, low calcium, and vitamin D deficiency. These imbalances result in parathyroid hyperplasia and contribute to vascular calcification. New studies have established a central role for fibroblast growth factor 23 (FGF-23) in the regulation of phosphate-vitamin D homeostasis. FGF-23 concentration increases in CKD and contributes to SHPT. Achieving current targets for the key mineral parameters in the management of SHPT set by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines can be challenging. This review summarizes the current understanding and evidence supporting strategies for SHPT treatment in CKD patients. Treatment should include a combination of dietary phosphorus restriction, phosphate binders, vitamin D sterols, and calcimi-metics. Parathyroidectomy is effective in suitable candidates refractory to medical therapy and the standard against which new approaches should be measured. Future strategies may focus on the stimulation of apopto-tic activity of hyperplastic parathyroid cells. © 2011 by the American Society of Nephrology.

De Francisco A.L.M.,Hospital Universitario Marques Of Valdecilla | Rodriguez M.,Hospital Universitario Reina Sofia
Nefrologia | Year: 2013

Magnesium containing compounds present promising oral phosphate binders for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). However, the impact of magnesium in CKD patients still remains unclear in clinical routine practice. Therefore, this publication provides a practicable overview of knowledge about the physiological role of magnesium in general and in particular in CKD patients. Prevalence of hypomagnesaemia is high in the general population and especially in intensive care unit patients, but often not being detected. Magnesium deficiency increases the risk for several diseases, like diabetes mellitus type 2, hypertension and atherosclerosis. Moderate hypermagnesaemia, however, seems to have beneficial effects on vascular calcification and mortality rates in CKD patients. On the other hand, higher serum magnesium levels are reported to be linked to lower PTH levels and results on the effects on bone are controversial. In addition, low magnesium levels are associated with low bone mass, osteoporosis and vascular calcification. In dialysis patients serum magnesium levels are dependent mainly on the dialysate magnesium concentration. To confirm the potential delay of arterial calcification and improved survival outcomes by long-term intervention with magnesium powered randomized studies are required in dialysis patients. Since a recent trial revealed that a phosphate binder containing a combination of magnesium carbonate and calcium acetate was as effective as the polymer-based agent sevelamer hydrochloride and had an equally good tolerability profile, it is time for a re-examination of the role of magnesium in CKD patients. © 2013 Revista Nefrología. Órgano Oficial de la Sociedad Española de Nefrología.

Tena-Sempere M.,University of Cordoba, Spain | Tena-Sempere M.,CIBER ISCIII | Tena-Sempere M.,Hospital Universitario Reina Sofia
Current Topics in Developmental Biology | Year: 2013

Puberty is the culmination of a complex series of maturational events that lead to the completion of sexual and somatic maturation and the acquisition of reproductive competence. This key developmental transition, which defines the boundary between immaturity and adulthood, is under the control of sophisticated regulatory networks that impinge upon the brain centers governing the reproductive axis. These networks are sensitive to earlier maturational events, such as brain sex differentiation, and dynamically regulated by a plethora of hormonal factors and environmental signals, which are essential for the fine-tuning of the tempo of puberty. While much knowledge on mammalian puberty had been gleaned during the last decades, important recent developments have substantially expanded our understanding of the neuroendocrine and molecular mechanisms governing puberty onset. We will provide here a synoptic account of some of these important advancements, including the identification of the essential roles of hypothalamic kisspeptin signaling, and some of its putative partners, in pubertal maturation, the characterization of novel mechanisms involved in the metabolic regulation of puberty, and the recognition of the potential roles of epigenetics and miRNA-related pathways in the central control of puberty. It is expected that further progress in these and related areas will follow in the coming years. This will permit a better understanding of the physiological mechanisms responsible for pubertal timing and will help to decipher the pathophysiological basis for pubertal alterations in humans and wildlife species. © 2013 Elsevier Inc.

Jimenez F.,Mediteknia Dermatology Clinic | Poblet E.,Hospital Universitario Reina Sofia | Izeta A.,Hospital Universitario Donostia
Experimental Dermatology | Year: 2015

Clinicians have long reported that hair-bearing areas tend to heal more rapidly than those lacking hair follicles. In the past decade, numerous scientific studies have corroborated clinical evidence, showing a direct nexus between the human hair follicle and the wound healing process. The migration of epithelial follicular stem cells to the skin surface to help in the wound re-epithelialization and the effect of the hair cycle on the wound healing rate underline the influence of the hair follicle in the healing process. In clinical practice, non-healing wounds are pathologies of high prevalence with significant associated burden costs for the healthcare system. As the population ages, the prevalence of this pathology is expected to increase in future years. The recent advances in understanding the biology of hair follicle stem cells have created the challenges of using this newly acquired knowledge in practical therapeutic applications. Chronic leg ulcers are an example of the targeted pathologies that urgently need better therapies. In this essay, our aim is to raise interest in this question, reviewing what is known in relation to the connections between hair follicles and wound healing, and elaborating on future directions that the field might take, including implications for clinical practice. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Santiago-Mora R.,Hospital Universitario Reina Sofia | Casado-Diaz A.,Hospital Universitario Reina Sofia | De Castro M.D.,University of Cordoba, Spain | Quesada-Gomez J.M.,Hospital Universitario Reina Sofia
Osteoporosis International | Year: 2011

Summary: The effects of oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells (MSCs) from human bone marrow have been studied. We report that oleuropein, a polyphenol abundant in olive tree products, reduces the expression of peroxisome proliferator-activated receptor gamma (PPARγ), inhibits adipocyte differentiation, and enhances differentiation into osteoblast. Introduction: Age-related bone loss is associated with osteoblast insufficiency during continuous bone remodeling. It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and age-related changes in this relationship could be responsible for the progressive adiposity of bone marrow which occurs with osteoporosis. In addition, the consumption of oleuropein, a major polyphenol in olive leaves and olive oil, has been associated with a reduction in bone loss. Methods: We have analyzed the effects of oleuropein-at concentrations between 10 -6 and 10 -4 M-on the processes of osteoblastogenesis and adipogenesis in MSCs from human bone marrow. Results: The results show an increase in osteoblast differentiation and a decrease in adipocyte differentiation when there is oleuropein in the culture media. The gene expression of osteoblastogenesis markers, RUNXII, osterix, collagen type I, osteocalcin, or alkaline phosphatase (ALP), was higher in osteoblast-induced oleuropein-treated cells. Also, the ALP activity and extracellular matrix mineralization were higher when oleuropein was present in the media. Oleuropein in MSCs induced adipocytes to produce a decrease in the expression of the genes involved in adipogenesis, the PPARγ, lipoprotein lipase, or fatty acid-binding protein 4, and minor fat accumulation. Conclusion: Our data suggest that oleuropein, highly abundant in olive tree products included in the traditional Mediterranean diet, could prevent age-related bone loss and osteoporosis. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.

Codner E.,University of Chile | Merino P.M.,University of Chile | Tena-Sempere M.,University of Cordoba, Spain | Tena-Sempere M.,CIBER ISCIII | Tena-Sempere M.,Hospital Universitario Reina Sofia
Human Reproduction Update | Year: 2012

Background: The functional reproductive alterations seen in women with type 1 diabetes (T1D) have changed as therapy has improved. Historically, patients with T1D and insufficient metabolic control exhibited a high prevalence of amenorrhea, hypogonadism and infertility. This paper reviews the impact of diabetes on the reproductive axis of female T1D patients treated with modern insulin therapy, with special attention to the mechanisms by which diabetes disrupts hypothalamic-pituitary-ovarian function, as documented mainly by animal model studies. Methods: A comprehensive MEDLINE search of articles published from 1966 to 2012 was performed. Animal model studies on experimental diabetes and human studies on T1D were examined and cross-referenced with terms that referred to different aspects of the gonadotropic axis, gonadotrophins and gonadal steroids. Results: Recent studies have shown that women with T1D still display delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. Animal models have helped us to decipher the underlying basis of these conditions and have highlighted the variable contributions of defective leptin, insulin and kisspeptin signalling to the mechanisms of perturbed reproduction in T1D. Conclusions: Despite improvements in insulin therapy, T1D patients still suffer many reproductive problems that warrant specific diagnoses and therapeutic management. Similar to other states of metabolic stress, T1D represents a challenge to the correct functioning of the reproductive axis. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

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