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Laura W.,Agrenvec S.L. | Pablo L.,Agrenvec S.L. | Arantxa A.,Agrenvec S.L. | Isabel B.,Agrenvec S.L. | And 7 more authors.
Current Pharmaceutical Biotechnology | Year: 2016

The design and development of novel biological drugs are among the most exciting new areas of biotechnology which are gaining the attention of scientists. In the last few decades several fabrication processes have been proposed and developed for the production of recombinant growth factors. However, traditional production processes have several limitations in terms of scale- up, cost-efficiency and purity grade of the proteins. In the present study, we propose for the first time the proof-of-concept of large-scale production of growth factors in plants as a new alternative to other production processes. We have decided to select vascular endothelial growth factor (VEGF) as model assuming its key role in cell survival and regenerative medicine. Results show that the present protocol is efficient to scale up a purification procedure of rh VEGF isoform 165 in Nicotiana benthamiana plants. Our procedure resulted in dimeric VEGF protein with high purity degree and yield, which showed full biological activity over endothelial and epithelial cells, suggesting great potential for its use in regenerative medicine. This protein could be exploited not only in tissue repair and regeneration but also as a biologically active ingredient in dermocosmetics. © 2016 Bentham Science Publishers.

Cobos Campos R.,Health Research Unit of Alava | Parraza Diez N.,Network Center for Biomedical Research in Epidemiology and Public Health | Aizpuru Barandiaran F.,University of the Basque Country
Wounds | Year: 2013

Introduction. Chronic vascular ulcers are associated with a high use of resources. Conventional treatment consists of wound cleansing, necrotic tissue debridement, prevention, diagnosis, and, if necessary, treatment of infection and dressing application; although conventional treatment has limited effectiveness with wound healing (around 15-30%).8-11 Platelet-rich plasma, used in various fields of medicine, improves chronic vascular ulcer results, but is more expensive. Methods. A cost-effectiveness analysis was performed using a 48-week period comparing plateletrich plasma with standard care. A meta-analysis of papers identified by a literature search was done. Results. A combined measure of effectiveness at 12 weeks for each treatment option was calculated and served as the basis for estimating the probability of healing at 48 weeks with a Markov model. Conclusions. The probability of healing and associated costs were 56% and €5224 using platelet-rich plasma and 31% and €5133 with usual care. The incremental cost that must be assumed to achieve additional healing with platelet-rich plasma is €364.

Cobos R.,Health Research Unit of Alava | Aizpuru F.,Health Research Unit of Alava | Parraza N.,Health Research Unit of Alava | Anitua E.,Eduardo Anitua Foundation for Biomedical Research | And 2 more authors.
Current Pharmaceutical Biotechnology | Year: 2015

 “There is a growing body of evidence suggesting that wound healing in chronic diabeticfoot ulcers is growth factor dependent, and that the therapeutic delivery of these growth factors towounds topically, has the potential ability to accelerate wound healing in conjunction with conventionalwound care”. There is, however, confusion about the utility of platelet rich plasma because thestudies that have evaluated them use a wide range of products (different platelet and leukocyte concentrations, differenttechniques and frequencies of application, very heterogeneous simple, and different endpoints) making almost impossibleto compare data and draw conclusions. In this study, we have analyzed the different platelet rich plasma products from anew perspective: cost-efficiency. According to our data, we observe that platelet rich plasma is a cost-effective option thatallows faster healing of ulcers, and that should be taken into account in patients with long evolution ulcers. © 2015 Bentham Science Publishers.

Cobos R.,Health Research Unit of Alava | Latorre A.,Health Research Unit of Alava | Aizpuru F.,Health Research Unit of Alava | Aizpuru F.,CIBER ISCIII | And 9 more authors.
BMC Musculoskeletal Disorders | Year: 2010

Background. Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication. Methods. The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated. The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ5-95), variation coefficient (CV 5-95) and weighted variation coefficient (WCV5-95) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV5-95. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity. Results. The variability expressed as WCV5-95 was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate. Conclusions. A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates. © 2010 Cobos et al; licensee BioMed Central Ltd.

Serrano A.J.,University of the Basque Country | Cobos R.,Health Research Unit of Alava | Orive G.,University of the Basque Country | Orive G.,CIBER ISCIII
Gynecological Endocrinology | Year: 2013

The aim of this meta-analysis was to evaluate the efficacy and safety of two bisphosphonates (alendronate and zoledronate) in the treatment of postmenopausal osteoporosis. The incidence of fractures was considered as primary endpoint. Only randomized trials with a follow-up period of 1 year or more were included in this systematic review and meta-analysis. We excluded studies that included patients with secondary osteoporosis especially in relation to therapy with corticosteroids or other drugs or diseases known to affect bone mineral density. Studies published as subgroup analysis, extension studies, economic evaluations, and comparisons with active control were excluded. The methodological quality of controlled clinical trials that met these inclusion criteria was evaluated. No studies were excluded from analysis due to lack of quality. The risk ratio of hip, vertebral and wrist fractures for alendronate were 0.61 [95% confidence interval (CI) 0.40-0.93], 0.54 (95% CI 0.44-0.66) and 0.65 (95% CI 0.33-1.25), respectively. Zoledronate risk ratio was 0.62 (95% CI 0.46-0.82) and 0.38 (95% CI 0.22-0.67) for hip and vertebral fractures, respectively. © 2013 Informa UK Ltd.

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