Scientific evidence links physical activity to several benefits. Recently, we proposed the idea t... more Scientific evidence links physical activity to several benefits. Recently, we proposed the idea that exercise can be regarded as a drug. As with many drugs, dosage is of great importance. However, to issue a public recommendation of physical activity in aging is not an easy task. Exercise in the elderly needs to be carefully tailored and individualized with the specific objectives of the person or group in mind. The beneficial effects of exercise in two of the main age-related diseases, sarcopenia and Alzheimer's Disease, are dealt with at the beginning of this report. Subsequently, dosage of exercise and the molecular signaling pathways involved in its adaptations are discussed. Exercise and aging are associated with oxidative stress so the paradox arises, and is discussed, as to whether exercise would be advisable for the aged population from an oxidative stress point of view. Two of the main redox-sensitive signaling pathways altered in old skeletal muscle during exercise, NF-κB and PGC-1α, are also reviewed. The last section of the manuscript is devoted to the age-associated diseases in which exercise is contraindicated. Finally, we address the option of applying exercise mimetics as an alternative for disabled old people. The overall denouement is that exercise is so beneficial that it should be deemed a drug both for young and old populations. If old adults adopted a more active lifestyle, there would be a significant delay in frailty and dependency with clear benefits to individual well-being and to the public's health.
The use of [(99m)Tc]glucarate has been reported as an infarct-avid agent with the potential for v... more The use of [(99m)Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [(99m)Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [(99m)Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors. Glucarate in a kit formulation was labeled with (99m)Tc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [(99m)Tc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a micro-single photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis...
Females live longer than males. Oestrogens protect females against aging by up-regulating the exp... more Females live longer than males. Oestrogens protect females against aging by up-regulating the expression of antioxidant, longevity-related genes such as glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). The mechanism through which oestrogens up-regulate those enzymes remains unidentified, but may have implications for gender differences in lifespan. We show that physiological concentrations of oestradiol act through oestrogen receptors to reduce peroxide levels in MCF-7 cells (a mammary gland tumour cell line). Oestradiol increases MAP kinase (MAPK) activation as indicated by ERK1 and ERK2 phosphorylation in MCF-7 cells, which in turn activates the nuclear factor kappa B (NFkappaB) signalling pathways as indicated by an increase in the p50 subunit of NFkappaB in nuclear extracts. Blockade of MAPK and NFkappaB signalling reduces the antioxidant effect of oestradiol. Finally, we show that activation of MAPK and NFkappaB by oestrogens drives the expression of the antio...
Science of aging knowledge environment : SAGE KE, Jan 8, 2005
Females live longer than males in many species, including humans. We have traced a possible expla... more Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males.
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological proc... more RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging, lifespan and metabolic parameters were analyzed in aged RasGrf1(-/-) mice. We observed that mice deficient for RasGrf1(-/-) display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals. Aged RasGrf1(-/-) displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1(-/-). IGF-I levels were lower in RasGrf1(-/-) than in controls. Furthermore, SIRT1 expression was increased in RasGrf1(-/-) animals. Consistent with this, the blood metabolomic profiles of RasGrf1-deficient mice resembled those observed in calorie-restricted animals. In addition, cardiac glucose consumption as d...
Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts... more Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts, mulberries, blueberries and, above all, in grapes and red wine. Its synthesis is regulated by the presence of stressful factors, such as fungal contamination and ultra-violet radiation. In plants, it plays a role as a phytoalexin, showing a capacity to inhibit the development of certain infections. Plant extracts which contain resveratrol have been employed by traditional medicine for more than 2000 years. Resveratrol was first isolated, and its properties were initially studied with scientific methods, thirty years ago. Its in vitro properties have been extensively studied and demonstrated. It is worth highlighting its activity as an anti-cancer agent, platelet anti-aggregation agent, anti-inflammatory, antiallergenic, etc. The activity of its in vivo properties are not so clear. There are many studies that report benefits on the cardiovascular system, illnesses such as diabetes, and ...
Journal of Clinical and Experimental Dentistry, 2014
The aim of this work was to review de literature about the role of mesenchymal stem cells in bone... more The aim of this work was to review de literature about the role of mesenchymal stem cells in bone regenerative procedures in oral implantology, specifically, in the time require to promote bone regeneration. [corrected] A bibliographic search was carried out in PUBMED with a combination of different key words. Animal and human studies that assessed histomorphometrically the influence of mesenchymal stem cells on bone regeneration procedures in oral implantology surgeries were examined. Reults: - Alveolar regeneration: Different controlled histomorphometric animal studies showed that bone regeneration is faster using stem cells seeded in scaffolds than using scaffolds or platelet rich plasma alone. Human studies revealed that stem cells increase bone regeneration. - Maxillary sinus lift: Controlled studies in animals and in humans showed higher bone regeneration applying stem cells compared with controls. - Periimplantary bone regeneration and alveolar distraction: Studies in animals showed higher regeneration when stem cells are used. In humans, no evidence of applying mesenchymal stem cells in these regeneration procedures was found. Stem cells may promote bone regeneration and be useful in bone regenerative procedures in oral implantology, but no firm conclusions can be drawn from the rather limited clinical studies so far performed. Key words:Mesenchymal stem cells, bone regeneration, dental implants, oral surgery, tissue engineering.
Antioxidant properties of resveratrol have been intensively studied for the last years, both in v... more Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant. In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect. We used mammary gland tumor cells (MCF-7), which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy). Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM). This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels. Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway.
Revista Española de Geriatría y Gerontología, 2010
El anciano en situación crítica: nuevos retos en la asistencia geriátrica del futuro A. López-Sot... more El anciano en situación crítica: nuevos retos en la asistencia geriátrica del futuro A. López-Soto y E. Sacanella
High rates of stem cell proliferation are important in regenerative medicine and in stem cell ban... more High rates of stem cell proliferation are important in regenerative medicine and in stem cell banking for clinical use. Ambient oxygen tensions (21% O2) are normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% O2. We compared proliferation of human dental pulp stem cells (hDPSCs) cultured under 21% versus 3% O2. The rate of hDPSC proliferation is significantly lower at 21% O2 compared to physiological oxygen levels due to enhanced oxidative stress. Under 21% O2, increased p38 phosphorylation led to activation of p21. Increased generation of reactive oxygen species and p21 led to activation of the NRF-2 signaling pathway. The upregulation of NRF-2 antioxidant defense genes under 21% O2 may interact with cell-cycle-related proteins involved in regulating cell proliferation. Activation of p38/p21/NRF-2 in hDPSCs cultured under ambient oxygen tension inhibits stem cell proliferation and upregulates NRF-2 antioxidant defenses.
All books in this series illustrate point-of-care testing and critically evaluate the potential o... more All books in this series illustrate point-of-care testing and critically evaluate the potential of antioxidant supplementation in various medical disorders associated with oxidative stress. Future volumes will be updated as warranted by emerging new technology, or from studies reporting clinical trials.
Dendron-bearing Cetuximab is thus used for treatment of colon, head, and neck cancer, so as to co... more Dendron-bearing Cetuximab is thus used for treatment of colon, head, and neck cancer, so as to combine high specific activities brought by multilabeling to achieve a more effective targeted radionuclide therapy as it has been shown for Zevalin and Rituximab. The dendron to antibody ratio was determined by MALDI-TOF MS. These new conjugates have been radiolabeled by 64 Cu and 90 Y and higher specific activities have been obtained compared to monochelator-labeled antibody. positron emission tomography imaging in mice showed a significant tumour accumulation. Here we discuss the relationships between dendron to antibody ratio, antigen affinity and specific activity of monochelator and dendron-labeled Cetuximab conjugates.
Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer&a... more Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip strength and some exacerbation of the behavioral and psychological symptoms of dementia (BPSD)-like involving active exploratory activities. A similar major cognitive impairment was observed of ovariectomized 3xTg-AD mice in comparison with sham-operated 3xTg-AD mice. A reduction of bodily fitness and lack of retention of memory were observed in the ovariectomized non-transgenic mice. Physical exercise protected against all deleterious behaviors and normalized learning and memory. It also protected against body frailty, as expected. Analyses of hippocampal key markers of antioxidant and neuroplasticity signaling pathways, showed that ovariectomy impairs the activation of CREB through physical exercise. Furthermore, molecular and behavioral correlates suggested a central role of BDNF in the neuroprotection mediated by physical exercise therapy against apathy and memory loss induced by ovariectomy and the AD-genotype.
Introduction: The use of [ 99m Tc]glucarate has been reported as an infarct-avid agent with the p... more Introduction: The use of [ 99m Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [ 99m Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [ 99m Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors. Methods: Glucarate in a kit formulation was labeled with 99m Tc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [ 99m Tc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a microsingle photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis and metastatic deposit localization. Results: The Glucarate kits exhibited a stable shelf life of 6 months. [ 99m Tc]Glucarate was obtained with radiochemical purity greater than 95%. Biodistribution studies demonstrated moderate tumor uptake coupled with high renal clearance. Tumor-to-muscle ratios were 4.85 and 5.14 at 1 and 4 h post injection. MRI analysis showed tumors with dense cellular growth and moderate central necrosis. [ 99m Tc]Glucarate uptake in the primary MDA-MB-435 shoulder tumors and metastatic lesions were clearly visualized with micro-SPECT/CT imaging. Conclusions: Selective tumor uptake and rapid clearance from nontarget organs makes [ 99m Tc]glucarate a potential agent for breast cancer imaging that awaits validation in a clinical trial.
Preliminary findings have suggested that (99m)Tc-glucarate has tumor-seeking properties. The purp... more Preliminary findings have suggested that (99m)Tc-glucarate has tumor-seeking properties. The purpose of this study was to explore the potential of this tracer to evaluate malignant head and neck tumors by means of SPECT/CT software fusion imaging. Eleven male patients with advanced head and neck carcinoma were included in the study: 9 with locally advanced disease and 2 with clinical suspicion of local relapse. Scanning started 3-6 h after the injection of 1,110 MBq of (99m)Tc-glucarate. Planar and SPECT images of the head, neck, and thorax were acquired. Three-dimensional images were also coregistered with CT. We found (99m)Tc-glucarate uptake in all suspected lesions. SPECT/CT fusion imaging was helpful in all cases for topographically localizing the tracer foci. (99m)Tc-glucarate can be considered a potential tracer for the evaluation of patients with head and neck tumors.
Hormone Molecular Biology and Clinical Investigation, 2000
Abstract Females live longer than males. We have shown that this could be in part due to the high... more Abstract Females live longer than males. We have shown that this could be in part due to the higher levels of oestrogens in females, which protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. However, the low concentration of oestrogens makes it unlikely that they exhibit significant antioxidant capacity in the organism. Our results show that physiological concentrations of oestrogens activate the expression of manganese superoxide dismutase and glutathione peroxidase by oestrogen receptors and the mitogen-activated protein kinase and nuclear factor kappa B pathway. Moreover, when considering oestrogen replacement therapy, it is of utmost importance to take into account when to start the therapy after menopause. We have shown that only early-onset administration of oestrogen replacement therapy is effective on oestrogen deprivation associated with oxidative and metabolic stress. This is due to a change in oestrogen receptor distribution after oestrogen deprivation. Oestrogens are also involved in inflammatory processes. Their role on inflammation is very complex, because their effects are different depending on the doses and also on the oestrogen receptor distribution.
Females live longer than males in many mammalian species, including humans. This natural phenomen... more Females live longer than males in many mammalian species, including humans. This natural phenomenon can be explained on the basis of the mitochondrial theory of aging. Mitochondria are a major source of free radicals in cells. Mitochondria from female rats generate half the amount of hydrogen peroxide than those of males and have higher levels of mitochondrial reduced glutathione. The latter is due to females behaving as double transgenic in over-expressing antioxidant enzymes. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NFkappaB) signalling pathways, resulting in an upregulation of antioxidant enzymes. Moreover, the 16S rRNA expression, which decreases significantly with aging, is four times higher in mitochondria from females than in those from males of the same chronological age. On the contrary, the oxidative damage of mitochondrial DNA is fourfold higher in males than in females. Ovariectomy abolishes the gender differences between males and females and estrogen replacement rescues the effect of ovariectomy. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.
Females live longer than males. Work from our laboratory has shown that this may be due to the up... more Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevityassociated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes.
The validity of the free radical theory of aging has been recently questioned. Our aim was to tes... more The validity of the free radical theory of aging has been recently questioned. Our aim was to test whether there is oxidative stress in tissues critically involved in accelerated aging (senescence-accelerated mice, SAM) and whether this correlates with lower glucose consumption in vivo and behavioural tests. Positron emission tomography shows that brains of old SAM-prone animals consume less glucose than young ones. Behavioural characteristics, mitochondrial peroxide production, and damage in both the central nervous system and bone marrow stem cells also indicate that SAM-prone animals age faster than SAM-resistant ones. Our results support the role of the free radical theory of aging in critical tissues involved in aging and that this correlates with glucose consumption.
Females live longer than males in many mammalian species, including humans. Mitochondria from fem... more Females live longer than males in many mammalian species, including humans. Mitochondria from females produce approximately half the amount of H 2 O 2 than males. We have found that females behave as double transgenics overexpressing both superoxide dismutase and glutathione peroxidase. This is due to oestrogens that act by binding to the estrogen receptors and subsequently activating the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-jB) signalling pathways. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed.
Scientific evidence links physical activity to several benefits. Recently, we proposed the idea t... more Scientific evidence links physical activity to several benefits. Recently, we proposed the idea that exercise can be regarded as a drug. As with many drugs, dosage is of great importance. However, to issue a public recommendation of physical activity in aging is not an easy task. Exercise in the elderly needs to be carefully tailored and individualized with the specific objectives of the person or group in mind. The beneficial effects of exercise in two of the main age-related diseases, sarcopenia and Alzheimer's Disease, are dealt with at the beginning of this report. Subsequently, dosage of exercise and the molecular signaling pathways involved in its adaptations are discussed. Exercise and aging are associated with oxidative stress so the paradox arises, and is discussed, as to whether exercise would be advisable for the aged population from an oxidative stress point of view. Two of the main redox-sensitive signaling pathways altered in old skeletal muscle during exercise, NF-κB and PGC-1α, are also reviewed. The last section of the manuscript is devoted to the age-associated diseases in which exercise is contraindicated. Finally, we address the option of applying exercise mimetics as an alternative for disabled old people. The overall denouement is that exercise is so beneficial that it should be deemed a drug both for young and old populations. If old adults adopted a more active lifestyle, there would be a significant delay in frailty and dependency with clear benefits to individual well-being and to the public's health.
The use of [(99m)Tc]glucarate has been reported as an infarct-avid agent with the potential for v... more The use of [(99m)Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [(99m)Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [(99m)Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors. Glucarate in a kit formulation was labeled with (99m)Tc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [(99m)Tc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a micro-single photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis...
Females live longer than males. Oestrogens protect females against aging by up-regulating the exp... more Females live longer than males. Oestrogens protect females against aging by up-regulating the expression of antioxidant, longevity-related genes such as glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). The mechanism through which oestrogens up-regulate those enzymes remains unidentified, but may have implications for gender differences in lifespan. We show that physiological concentrations of oestradiol act through oestrogen receptors to reduce peroxide levels in MCF-7 cells (a mammary gland tumour cell line). Oestradiol increases MAP kinase (MAPK) activation as indicated by ERK1 and ERK2 phosphorylation in MCF-7 cells, which in turn activates the nuclear factor kappa B (NFkappaB) signalling pathways as indicated by an increase in the p50 subunit of NFkappaB in nuclear extracts. Blockade of MAPK and NFkappaB signalling reduces the antioxidant effect of oestradiol. Finally, we show that activation of MAPK and NFkappaB by oestrogens drives the expression of the antio...
Science of aging knowledge environment : SAGE KE, Jan 8, 2005
Females live longer than males in many species, including humans. We have traced a possible expla... more Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males.
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological proc... more RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging, lifespan and metabolic parameters were analyzed in aged RasGrf1(-/-) mice. We observed that mice deficient for RasGrf1(-/-) display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals. Aged RasGrf1(-/-) displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1(-/-). IGF-I levels were lower in RasGrf1(-/-) than in controls. Furthermore, SIRT1 expression was increased in RasGrf1(-/-) animals. Consistent with this, the blood metabolomic profiles of RasGrf1-deficient mice resembled those observed in calorie-restricted animals. In addition, cardiac glucose consumption as d...
Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts... more Resveratrol is a natural polyphenol which can be found in many plants and fruits, such as peanuts, mulberries, blueberries and, above all, in grapes and red wine. Its synthesis is regulated by the presence of stressful factors, such as fungal contamination and ultra-violet radiation. In plants, it plays a role as a phytoalexin, showing a capacity to inhibit the development of certain infections. Plant extracts which contain resveratrol have been employed by traditional medicine for more than 2000 years. Resveratrol was first isolated, and its properties were initially studied with scientific methods, thirty years ago. Its in vitro properties have been extensively studied and demonstrated. It is worth highlighting its activity as an anti-cancer agent, platelet anti-aggregation agent, anti-inflammatory, antiallergenic, etc. The activity of its in vivo properties are not so clear. There are many studies that report benefits on the cardiovascular system, illnesses such as diabetes, and ...
Journal of Clinical and Experimental Dentistry, 2014
The aim of this work was to review de literature about the role of mesenchymal stem cells in bone... more The aim of this work was to review de literature about the role of mesenchymal stem cells in bone regenerative procedures in oral implantology, specifically, in the time require to promote bone regeneration. [corrected] A bibliographic search was carried out in PUBMED with a combination of different key words. Animal and human studies that assessed histomorphometrically the influence of mesenchymal stem cells on bone regeneration procedures in oral implantology surgeries were examined. Reults: - Alveolar regeneration: Different controlled histomorphometric animal studies showed that bone regeneration is faster using stem cells seeded in scaffolds than using scaffolds or platelet rich plasma alone. Human studies revealed that stem cells increase bone regeneration. - Maxillary sinus lift: Controlled studies in animals and in humans showed higher bone regeneration applying stem cells compared with controls. - Periimplantary bone regeneration and alveolar distraction: Studies in animals showed higher regeneration when stem cells are used. In humans, no evidence of applying mesenchymal stem cells in these regeneration procedures was found. Stem cells may promote bone regeneration and be useful in bone regenerative procedures in oral implantology, but no firm conclusions can be drawn from the rather limited clinical studies so far performed. Key words:Mesenchymal stem cells, bone regeneration, dental implants, oral surgery, tissue engineering.
Antioxidant properties of resveratrol have been intensively studied for the last years, both in v... more Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant. In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect. We used mammary gland tumor cells (MCF-7), which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy). Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM). This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels. Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway.
Revista Española de Geriatría y Gerontología, 2010
El anciano en situación crítica: nuevos retos en la asistencia geriátrica del futuro A. López-Sot... more El anciano en situación crítica: nuevos retos en la asistencia geriátrica del futuro A. López-Soto y E. Sacanella
High rates of stem cell proliferation are important in regenerative medicine and in stem cell ban... more High rates of stem cell proliferation are important in regenerative medicine and in stem cell banking for clinical use. Ambient oxygen tensions (21% O2) are normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% O2. We compared proliferation of human dental pulp stem cells (hDPSCs) cultured under 21% versus 3% O2. The rate of hDPSC proliferation is significantly lower at 21% O2 compared to physiological oxygen levels due to enhanced oxidative stress. Under 21% O2, increased p38 phosphorylation led to activation of p21. Increased generation of reactive oxygen species and p21 led to activation of the NRF-2 signaling pathway. The upregulation of NRF-2 antioxidant defense genes under 21% O2 may interact with cell-cycle-related proteins involved in regulating cell proliferation. Activation of p38/p21/NRF-2 in hDPSCs cultured under ambient oxygen tension inhibits stem cell proliferation and upregulates NRF-2 antioxidant defenses.
All books in this series illustrate point-of-care testing and critically evaluate the potential o... more All books in this series illustrate point-of-care testing and critically evaluate the potential of antioxidant supplementation in various medical disorders associated with oxidative stress. Future volumes will be updated as warranted by emerging new technology, or from studies reporting clinical trials.
Dendron-bearing Cetuximab is thus used for treatment of colon, head, and neck cancer, so as to co... more Dendron-bearing Cetuximab is thus used for treatment of colon, head, and neck cancer, so as to combine high specific activities brought by multilabeling to achieve a more effective targeted radionuclide therapy as it has been shown for Zevalin and Rituximab. The dendron to antibody ratio was determined by MALDI-TOF MS. These new conjugates have been radiolabeled by 64 Cu and 90 Y and higher specific activities have been obtained compared to monochelator-labeled antibody. positron emission tomography imaging in mice showed a significant tumour accumulation. Here we discuss the relationships between dendron to antibody ratio, antigen affinity and specific activity of monochelator and dendron-labeled Cetuximab conjugates.
Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer&a... more Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip strength and some exacerbation of the behavioral and psychological symptoms of dementia (BPSD)-like involving active exploratory activities. A similar major cognitive impairment was observed of ovariectomized 3xTg-AD mice in comparison with sham-operated 3xTg-AD mice. A reduction of bodily fitness and lack of retention of memory were observed in the ovariectomized non-transgenic mice. Physical exercise protected against all deleterious behaviors and normalized learning and memory. It also protected against body frailty, as expected. Analyses of hippocampal key markers of antioxidant and neuroplasticity signaling pathways, showed that ovariectomy impairs the activation of CREB through physical exercise. Furthermore, molecular and behavioral correlates suggested a central role of BDNF in the neuroprotection mediated by physical exercise therapy against apathy and memory loss induced by ovariectomy and the AD-genotype.
Introduction: The use of [ 99m Tc]glucarate has been reported as an infarct-avid agent with the p... more Introduction: The use of [ 99m Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [ 99m Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [ 99m Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors. Methods: Glucarate in a kit formulation was labeled with 99m Tc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [ 99m Tc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a microsingle photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis and metastatic deposit localization. Results: The Glucarate kits exhibited a stable shelf life of 6 months. [ 99m Tc]Glucarate was obtained with radiochemical purity greater than 95%. Biodistribution studies demonstrated moderate tumor uptake coupled with high renal clearance. Tumor-to-muscle ratios were 4.85 and 5.14 at 1 and 4 h post injection. MRI analysis showed tumors with dense cellular growth and moderate central necrosis. [ 99m Tc]Glucarate uptake in the primary MDA-MB-435 shoulder tumors and metastatic lesions were clearly visualized with micro-SPECT/CT imaging. Conclusions: Selective tumor uptake and rapid clearance from nontarget organs makes [ 99m Tc]glucarate a potential agent for breast cancer imaging that awaits validation in a clinical trial.
Preliminary findings have suggested that (99m)Tc-glucarate has tumor-seeking properties. The purp... more Preliminary findings have suggested that (99m)Tc-glucarate has tumor-seeking properties. The purpose of this study was to explore the potential of this tracer to evaluate malignant head and neck tumors by means of SPECT/CT software fusion imaging. Eleven male patients with advanced head and neck carcinoma were included in the study: 9 with locally advanced disease and 2 with clinical suspicion of local relapse. Scanning started 3-6 h after the injection of 1,110 MBq of (99m)Tc-glucarate. Planar and SPECT images of the head, neck, and thorax were acquired. Three-dimensional images were also coregistered with CT. We found (99m)Tc-glucarate uptake in all suspected lesions. SPECT/CT fusion imaging was helpful in all cases for topographically localizing the tracer foci. (99m)Tc-glucarate can be considered a potential tracer for the evaluation of patients with head and neck tumors.
Hormone Molecular Biology and Clinical Investigation, 2000
Abstract Females live longer than males. We have shown that this could be in part due to the high... more Abstract Females live longer than males. We have shown that this could be in part due to the higher levels of oestrogens in females, which protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. However, the low concentration of oestrogens makes it unlikely that they exhibit significant antioxidant capacity in the organism. Our results show that physiological concentrations of oestrogens activate the expression of manganese superoxide dismutase and glutathione peroxidase by oestrogen receptors and the mitogen-activated protein kinase and nuclear factor kappa B pathway. Moreover, when considering oestrogen replacement therapy, it is of utmost importance to take into account when to start the therapy after menopause. We have shown that only early-onset administration of oestrogen replacement therapy is effective on oestrogen deprivation associated with oxidative and metabolic stress. This is due to a change in oestrogen receptor distribution after oestrogen deprivation. Oestrogens are also involved in inflammatory processes. Their role on inflammation is very complex, because their effects are different depending on the doses and also on the oestrogen receptor distribution.
Females live longer than males in many mammalian species, including humans. This natural phenomen... more Females live longer than males in many mammalian species, including humans. This natural phenomenon can be explained on the basis of the mitochondrial theory of aging. Mitochondria are a major source of free radicals in cells. Mitochondria from female rats generate half the amount of hydrogen peroxide than those of males and have higher levels of mitochondrial reduced glutathione. The latter is due to females behaving as double transgenic in over-expressing antioxidant enzymes. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NFkappaB) signalling pathways, resulting in an upregulation of antioxidant enzymes. Moreover, the 16S rRNA expression, which decreases significantly with aging, is four times higher in mitochondria from females than in those from males of the same chronological age. On the contrary, the oxidative damage of mitochondrial DNA is fourfold higher in males than in females. Ovariectomy abolishes the gender differences between males and females and estrogen replacement rescues the effect of ovariectomy. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.
Females live longer than males. Work from our laboratory has shown that this may be due to the up... more Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevityassociated genes by estrogens. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein kinase and nuclear factor kappa B signalling pathways, resulting in an up-regulation of antioxidant enzymes.
The validity of the free radical theory of aging has been recently questioned. Our aim was to tes... more The validity of the free radical theory of aging has been recently questioned. Our aim was to test whether there is oxidative stress in tissues critically involved in accelerated aging (senescence-accelerated mice, SAM) and whether this correlates with lower glucose consumption in vivo and behavioural tests. Positron emission tomography shows that brains of old SAM-prone animals consume less glucose than young ones. Behavioural characteristics, mitochondrial peroxide production, and damage in both the central nervous system and bone marrow stem cells also indicate that SAM-prone animals age faster than SAM-resistant ones. Our results support the role of the free radical theory of aging in critical tissues involved in aging and that this correlates with glucose consumption.
Females live longer than males in many mammalian species, including humans. Mitochondria from fem... more Females live longer than males in many mammalian species, including humans. Mitochondria from females produce approximately half the amount of H 2 O 2 than males. We have found that females behave as double transgenics overexpressing both superoxide dismutase and glutathione peroxidase. This is due to oestrogens that act by binding to the estrogen receptors and subsequently activating the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-jB) signalling pathways. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of upregulating antioxidant genes, by hormonal and dietary manipulations, in order to increase longevity is discussed.
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