Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates.

Alzheimer's disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic ß amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment.

Centenarians: An excellent example of resilience for successful ageing.

Centenarians are remarkable not only because of their prolonged life, but also because they compress morbidity until the very last moments of their lives, thus being proposed as a model of successful, extraordinary ageing. From the medical viewpoint, centenarians do not escape the physiological decline or the age-related diseases or syndromes (i.e. frailty), but the rate of such processes is slow enough to be counterbalanced by their increased intrinsic capacity to respond to minor stresses of daily life (i.e. resilience). These new concepts are reviewed in this paper. Allostatic stresses lead to a chronic low-grade inflammation that has led to the proposal of the "inflammaging" theory of ageing and frailty. The biology of centenarians, described in this review, provides us with clues for intervention to promote healthy ageing in the general population. One of the major reasons for this healthy ageing has to do with the genetic signature that is specific for centenarians and certainly different from octogenarians who do not enjoy the extraordinary qualities of centenarians.

Resveratrol shifts energy metabolism to increase lipid oxidation in healthy old mice.

OBJECTIVES: The objective of this work was to determine the specific mechanisms by which resveratrol inhibits lipogenesis and stimulates lipolysis. METHODS: Twelve male mice were individually introduced into a metabolic cage for 24 h to measure basal metabolic rate, prior to intervention. They were randomly divided into two groups, resveratrol (RSV) and control (C), and administered resveratrol intraperitoneally or vehicle, respectively, for two consecutive days. After 24 h, the metabolic energy expenditure was again determined for 24 h, before mice were sacrificed. Protein and gene expression of different enzymes related to metabolism in the hepatic tissue, adipose tissue and gastrocnemius of mice were analyzed by RT-PCR, western blot or ELISA. RESULTS: We report that resveratrol lowers the respiratory quotient in old mice and that this may be due to the activation of fatty acid mobilization from white adipose tissue (because hormone-activated lipase expression is increased) and fatty acid transport into mitochondria and eventual oxidation in muscle and liver (because transport enzymes and beta oxidation enzymes are also increased). Indeed, we have observed that resveratrol in vivo causes an increase in the expression and phosphorylation of AMPKα in liver, muscle and adipose tissue and an increase in the expression of acyl-CoA synthetase, of carnitine palmitoyl transferase 1 and of carnitine acylcarnitine translocase, all enzymes involved in lipid catabolism. On the other hand, the levels of acetyl-CoA carboxylase as well as those its product, i.e. malonyl CoA, are decreased. CONCLUSIONS: We conclude that a controlled dose of resveratrol activates fatty acid mobilization and degradation and inhibits fatty acid synthesis in old mice. This is the first time that these effects of resveratrol in lipid metabolism in healthy old (non-obese) animals are reported.

Exceptional human longevity is associated with a specific plasma phenotype of ether lipids.

A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state. This profile comprises higher level of alkyl forms derived from phosphatidylcholine with shorter number of carbon atoms and double bonds; and decreased content in alkenyl forms from phosphatidylethanolamine with longer chain length and higher double bonds. This compositional pattern suggests that ether lipids from centenarians are more resistant to lipid peroxidation, and that ether lipid signature expresses an optimized feature associated with exceptional human longevity. These results are in keeping with the free radical theory of aging.

Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians.

Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging).

Influence of different types of pulp treatment during isolation in the obtention of human dental pulp stem cells.

BACKGROUND: Different methods have been used in order to isolate dental pulp stem cells. The aim of this study was to study the effect of different types of pulp treatment during isolation, under 3% O2 conditions, in the time needed and the efficacy for obtaining dental pulp stem cells. MATERIAL AND METHODS: One hundred and twenty dental pulps were used to isolate dental pulp stem cells treating the pulp tissue during isolation using 9 different methods, using digestive, disgregation, or mechanical agents, or combining them. The cells were positive for CD133, Oct4, Nestin, Stro-1, CD34 markers, and negative for the hematopoietic cell marker CD-45, thus confirming the presence of mesenchymal stem cells. The efficacy of dental pulp stem cells obtention and the minimum time needed to obtain such cells comparing the 9 different methods was analyzed. RESULTS: Dental pulp stem cells were obtained from 97 of the 120 pulps used in the study, i.e. 80.8% of the cases. They were obtained with all the methods used except with mechanical fragmentation of the pulp, where no enzymatic digestion was performed. The minimum time needed to isolate dental pulp stem cells was 8 hours, digesting with 2mg/ml EDTA for 10 minutes, 4mg/ml of type I collagenase, 4mg/ml of type II dispase for 40 minutes, 13ng/ml of thermolysine for 40 minutes and sonicating the culture for one minute. CONCLUSIONS: Dental pulp stem cells were obtained in 97 cases from a series of 120 pulps. The time for obtaining dental pulp stem cells was reduced maximally, without compromising the obtention of the cells, by combining digestive, disgregation, and mechanical agents.

Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans.

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol.

High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease.

Susceptibility to invasive pneumococcal disease (IPD) correlates with age, younger children being the group with the highest burden of disease. The relevance of the innate immune response and particularly the role of mannose-binding lectin (MBL) in combating IPD is not well known. This is a 2-year prospective study (February 2011 to March 2013) including patients with IPD who attended two hospitals from Catalonia, Spain. Variables including attack rate of pneumococcal serotype (high or low invasive potential serotypes) and genotypes associated with low serum MBL levels were recorded. One hundred and forty-seven patients were included in the study. One hundred and two (69.4%) patients were children or adolescents <18 years and 45 (30.6%) were adults. Overall, low-MBL genotypes (O/O; XA/O) were detected in 23 (15.6%) patients. Children <2 years showed a higher frequency of low-MBL genotypes compared with other patients (31.0% vs. 11.9%; p = 0.031). Further sub-analysis revealed a higher proportion of low-MBL genotypes in children <2 years with IPD caused by opportunistic or low-attack-rate serotypes when compared with older patients (46.2% vs. 13.2%; p = 0.02). However, no statistically significant differences between the two groups were observed when including patients infected with invasive or high-attack-rate serotypes (18.8% vs. 10.0%; p = 0.59). Our data suggest that young children with a genetically determined low-MBL production are at a higher risk of developing IPD, particularly that caused by opportunistic or low-attack-rate pneumococcal serotypes.

Approaches to aspects of optimisation of protection in diagnostic radiology in six continents.

There has been an expansion in the use of x-ray imaging during the last 20 years. Effective arrangements for justification of exposures as well as for optimisation of protection are crucial. The amount of effort put into the latter, the way in which it is organised and the groups carrying this out vary across the globe. A simple survey of organisational arrangements relating to performance testing of x-ray equipment, management of patient dose and other aspects of implementing optimisation has been undertaken. A total of 137 completed survey forms were received from medical physicists in 48 countries. Results for individual countries from which more responses were received, or for groups of neighbouring ones, are compared to portray variations. Some performance testing of x-ray equipment was mandated in most countries (more than 90%), with the tests being performed primarily by hospital or private medical physicists, although other groups are involved. Testing of equipment prior to clinical use was generally high for most regions, but the frequency was lower in Latin America. There was considerable variation in the frequency and regularity of subsequent testing. The prevalence of patient dose surveys was high in Europe, but lower in other continents. Organisational arrangements for testing performance of x-ray equipment, patient dose surveys and implementing optimisation of protection in medical exposures across the globe can be divided into five main groups. Hospital medical physicists take the lead in western Europe and Australia with the involvement of radiographers. Private medical physicists test equipment in Brazil, the USA and New Zealand, and have some responsibility for optimisation in Brazil. University personnel have significant involvement, together with medical physicists in eastern Europe, but the extent of the coverage is uncertain. Government personnel and service engineers carry out equipment testing in many countries of Africa and Asia, while radiographers have a significant role in Thailand and other countries where the number of medical physicists is limited. In order for dose surveys to have an impact, action must be taken upon the findings, but there must be an effective link between surveyors and radiology facility staff to ensure that this is done.

Evolución de los ingresos por maltrato infantil durante 15 años / Hospital admissions due to child maltreatment over a fifteen year period

Objetivo: Determinar la evolución de la incidencia de ingresos por maltrato entre 1995 y 2009 y describir sus principales características clínicas y epidemiológicas. Métodos: Estudio retrospectivo de los niños con diagnóstico de alta de maltrato durante 15 años en un hospital de tercer nivel. Resultados: Se incluyen 97casos (incidencia mediana: 0,5 maltratos por 1.000 niños ingresados y año). Aumentan los ingresos por maltrato físico y disminuyen los de abuso sexual. Cincuenta y uno (53,6%) eran se sexo femenino; edad mediana 3.3 años (p25-75: 7,6 meses-10,0 años). El motivo de consulta no estaba relacionado con maltrato en 42 (43,3%) casos. Los hematomas (43; 44,3%) fueron las lesiones más frecuentes. En 91 (93,8%) casos el agresor fue un familiar (77; 74,9%, uno o ambos padres). Conclusiones: El aumento de ingresos por maltrato físico hace necesario insistir en políticas de prevención. La disminución en los casos de abusos sexuales probablemente sea más por cambios en los circuitos de atención a las víctimas que por una disminución real. En casi la mitad de los casos la sospecha surgió tras el examen físico o ante resultados de pruebas complementarias, siendo aconsejable tener presente el maltrato en el diagnóstico diferencial de múltiples motivos de consulta. La mayoría de los maltratos se producen dentro del entorno familiar(AU)

Aim: To measure the incidence of admissions for maltreatment between 1995 and 2009 and to determine their main clinical and epidemiological characteristics. Methods: Retrospective review of children diagnosed with maltreatment over 15years in a third level hospital. Results: A total of 97 cases (median incidence 0.5 cases per 1000 children admitted per year) were found. There was an increasing rate of physical maltreatment, while those of sexual abuse declined. 51 (53.6%) female; median age 3.3 years (p25-75: 7.6 months-10.0 years). Just under half (43.3%) or 42 patients, had a primary complaint unrelated to abuse. The most common injuries were haematomas (43; 44.3%). In 91 (93.8%) cases the perpetrator was found to be a member of the child's own family (77; 74.9%, one of the parents or both). Conclusions: The increase in admissions for physical maltreatment stresses the need to insist in a prevention policy. The decrease in admissions for sexual abuse was probably attributable to changes in the care circuit rather than a real decrease. In almost half of the cases the suspicion of maltreatment arose upon physical examination or after complementary tests, making it advisable that maltreatment is included in the differential diagnosis in multiple consultations. The majority of maltreatment occurred in the context of the victim's family(AU)

[Hospital admissions due to child maltreatment over a fifteen year period]. / Evolución de los ingresos por maltrato infantil durante 15 años.

AIM: To measure the incidence of admissions for maltreatment between 1995 and 2009 and to determine their main clinical and epidemiological characteristics. METHODS: Retrospective review of children diagnosed with maltreatment over 15 years in a third level hospital. RESULTS: A total of 97 cases (median incidence 0.5 cases per 1000 children admitted per year) were found. There was an increasing rate of physical maltreatment, while those of sexual abuse declined. 51 (53.6%) female; median age 3.3 years (p25-75: 7.6 months-10.0 years). Just under half (43.3%) or 42 patients, had a primary complaint unrelated to abuse. The most common injuries were haematomas (43; 44.3%). In 91 (93.8%) cases the perpetrator was found to be a member of the child's own family (77; 74.9%, one of the parents or both). CONCLUSIONS: The increase in admissions for physical maltreatment stresses the need to insist in a prevention policy. The decrease in admissions for sexual abuse was probably attributable to changes in the care circuit rather than a real decrease. In almost half of the cases the suspicion of maltreatment arose upon physical examination or after complementary tests, making it advisable that maltreatment is included in the differential diagnosis in multiple consultations. The majority of maltreatment occurred in the context of the victim's family.

Organ doses and risks of computed tomography examinations in Recife, Brazil.

Computed tomography (CT) examinations have increased significantly in recent years due to technological innovations. In some industrialised countries, CT contributes to the population dose as much as background radiation. In developing countries, the uses and risks of CT have not been well characterised. The purpose of this investigation was to assess potential stochastic and deterministic radiation effects from common CT exams performed in six hospitals of Recife, Pernambuco. Scanning parameters and patient gender and age were collected for a total of 285 patients undergoing CT examinations of the head (90), chest (75), abdomen (60) and abdomen-pelvis (60). The organ doses, which were calculated using the ImPACT dosimetry calculator, varied significantly among institutions. Organs such as the brain, the heart and the eye lenses, which exhibited doses as high as 85, 42 and 100 mGy, respectively, are of concern for the production of cerebrovascular and cardiovascular diseases and cataracts. Effective cancer risks were calculated using Brenner methodology and BEIR-VII risk factors. They range from 1.8 to 110.2 cases per 100000 persons for cancer induction and from 1.5 to 63.0 cases per 100000 for cancer mortality. To reduce doses, a quality assurance programme that includes procedural justification and radiation protection optimisation should be implemented.

Hormonal regulation of pro-inflammatory and lipid peroxidation processes in liver of old ovariectomized female rats.

There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in pro-inflammatory cytokines. On the other hand, oxidative stress has been implicated in the pathogenesis of several alterations due to menopause, and can arise through the increased production of lipid peroxides (LPO) and/or a deficiency of antioxidant defense. The aim of the present study was to investigate the effect of aging and ovariectomy on various physiological parameters related to inflammation and oxidative stress in livers obtained from old female rats and the influence of chronic exogenous administration of estrogens, phytoestrogens and growth hormone on these. Thirty-six female Wistar rats of 22 months of age were used in the present study. Twelve of them remained intact, and the other 24 had been ovariectomized at 12 months of age. Intact animals were divided into two groups and treated for 10 weeks with GH or saline, and ovariectomized animals were divided into four groups and treated for the same time with GH, estrogens, phytoestrogens or saline. A group of 2 month old intact female rats was used as young control. Protein expression of iNOS, HO-1, IL-6, TNFalpha, and IL-1beta were determined by Western blot analysis. The levels of NO( x ), LPO, TNFalpha, IL-1beta, IL-6 and IL-10 were determined in different fractions of the liver. Levels of LPO in the liver homogenates as well as iNOS protein expression and NO( x ) levels were increased in old rats as compared to young animals; this effect was more evident in ovariectomized animals. Pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 were significantly increased and anti-inflammatory IL-10 decreased during ageing and after ovariectomy. Aging also significantly increased expression of HO-1 protein and ovariectomized rats showed an additional increase. Hormonal administration to the ovariectomized groups decreased NO( x ), LPO levels and pro-inflammatory cytokines as compared with untreated rats. Significant rise in IL-10 and reductions in the iNOS, IL-6, TNFalpha and IL-1beta proteins expression were also found. Oxidative stress and inflammation induced during aging in the liver are more marked in castrated than in intact old females. Administration of the different hormonal replacement therapies was able to inhibit the induction of pro-inflammatory cytokines and iNOS, decreased the levels of oxidative stress markers and had therapeutic potential in the prevention of liver injury.

A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis.

Inflammation and neurodegeneration may have differential impacts on disease evolution in the different forms of multiple sclerosis. However, a beneficial effect of immunomodulatory drugs should not be ruled out in primary progressive multiple sclerosis. Our aim is to investigate the safety and efficacy of interferon beta-1b in primary progressive multiple sclerosis. We conducted a double-blind, stratified, randomized, parallel group, phase II pilot study where patients with primary progressive multiple sclerosis or 'transitional' forms of multiple sclerosis received interferon beta-1b at doses of 8 MIU or placebo for 24 months. The main objective of the study was to investigate the safety and tolerability of interferon beta-1b. The primary efficacy variable was the time to neurological deterioration (Expanded Disability Status Scale) confirmed at 3 months. Seventy-three patients were included and three dropped out the study. More patients in the treatment arm had at least one related adverse event (94.4% versus 45.9%; p < 0.001); no other significant differences in safety endpoints were observed. Time to neurological deterioration was not different between trial arms (log-rank test, p = 0.3135). Statistically significant differences favoring treatment were observed for the Multiple Sclerosis Functional Composite score at several timepoints, T1 and T2 lesion volume changes at 12 and 24 months, mean number of active lesions and proportion of patients with active lesions at 24 months. We conclude that interferon beta-1b is safe and well tolerated in patients with primary progressive multiple sclerosis and transitional multiple sclerosis. Positive effects of interferon beta on secondary clinical and magnetic resonance imaging outcomes were observed, but a beneficial effect on Expanded Disability Status Scale progression was not demonstrated.

Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection.

HIV-infected patients have a higher risk of developing cutaneous reactions than the general population, which has a significant impact on patients' current and future care options. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. HIV-infected patients just at the beginning of antiretroviral treatment can frequently show a wide variety of adverse drug effects such as drug rashes, hyperpigmentation, hair loss, hypersensitivity reactions, injection site reaction, urticarial reaction, erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome. The early detection and treatment of cutaneous adverse drug reactions, plus identification of the causative agent, are essential to prevent the progression of the reaction, preventing additional exposures and ensuring the appropriate use of medications for the current condition and keeping in mind others, such as patient age. This article emphasizes the most common features of an antiretroviral drug-induced cutaneous reaction from protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors, fusion inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors and inhibitors of the CCR5 chemokine receptor, paying special attention to the newest drugs approved for the treatment of HIV infection, such as tipranavir, darunavir, etravirine, enfuvirtide, raltegravir and maraviroc.

Abuso sexual infantil. Características de las consultas y manejo desde el servicio de urgencias / Child sexual abuse. Patient characteristics and management from the emergency department

Introducción: Los conflictos familiares podrían ser una de las causas del incremento delas consultas a urgencias por sospecha de abuso sexual. El objetivo de este trabajo es describir las características de los niños valorados en urgencias por sospecha de abusosexual. Método: Revisión retrospectiva de los casos valorados durante los primeros 7 meses de2004.Resultados: Se atendieron 48 consultas, dos por abuso agudo. La edad media fue de6,8 (SD 3,6 años), 42 fueron niñas. En el 85,4% la exploración física fue normal. Se completó el estudio en la Unidad multidisciplinar específica en 37 pacientes, 25 tenían a los padres separados. En 10 niñas el diagnóstico fue de abuso. Todos los agresores fueron hombres, principalmente familiares. No se hallaron diferencias entre la conclusión de abuso y el sexo del paciente, la presencia de una exploración física normal y la situación de separación de los padres. Conclusiones: En urgencias es difícil evaluar adecuadamente las consultas por abuso sexual. La mayoría no requieren actuación inmediata, y es imprescindible la actuación coordinada con Unidades multidisciplinares especializadas, que confirman un tercio delos casos. Las niñas son las principales víctimas y el agresor, una persona conocida (AU)

Background: Family conflicts may be one of the reasons for the increase in visits for suspected child sexual abuse in Emergency Departments. The aim of the study was to report the characteristics of the children who present to Emergency Department with suspected sexual abuse. Methods: Retrospective review of all the children evaluated for suspected sexual abuse in the Emergency Department during the first seven months of 2004.Results: A total of 48 patients were attended two for acute sexual abuse. The mean age was 6.8 years (SD 3.6 years),42 were girls. Physical examination was normal in 85.4%. The study was completed in the Multidisciplinary Abuse Unit in 37 patients; 25 of when had divorced parents. In 10 girls sexual abuse was established. All rapists were men, mainly relatives of the children. No differences were found in the diagnoses of abuse, patient sex, normal physical examination or the divorced state of the parents. Conclusions: Confirmation of suspected sexual abuse in the Emergency Department is difficult. Most cases do not require immediate intervention and cooperation with a Multidisciplinary Abuse Unit is necessary. One third of child abuse suspicions are confirmed. The victims are mainly girls and the aggressors are usually persons close to the children (AU)

Role of mitochondrial oxidative stress to explain the different longevity between genders: protective effect of estrogens.

Females live longer than males. Work from our laboratory has shown that this may be due to the up-regulation of longevity-associated 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. Estrogen administration, however, has serious undesirable effects and of course, cannot be administered to males because of its powerful feminizing effects. Thus, we tested the effect of genistein, a phytoestrogen of high nutritional importance whose structure is similar to estradiol, on the regulation of the expression of antioxidant, longevity-related genes and consequently on oxidant levels in mammary gland tumour cells in culture. Phytoestrogens mimic the protective effect of oestradiol using the same signalling pathway. The critical importance of up-regulating antioxidant genes, by hormonal and dietary manipulations, to increase longevity is discussed.

Long-term emotional state of multiple sclerosis patients treated with interferon beta.

OBJECTIVE: To assess the long-term emotional state of multiple sclerosis (MS) patients treated with interferon beta (IFNbeta) for at least four years. METHODS: Patients who had started IFNbeta therapy prior to 2000 with a baseline psychological assessment were identified and scheduled for long-term emotional assessment with the following questionnaires--the Hamilton Depression Rating Scale, the Beck Depression Inventory and the State-Trait Anxiety Inventory. RESULTS: A total of 262 patients started IFNbeta therapy in our MS clinic within the period 1995-1999. Baseline emotional assessment was available from 246 MS patients. Long-term assessment was conducted on 234 patients. After a mean follow-up of 65 months (43-98), 52 patients (22.3%) had withdrawn from IFNbeta therapy. The comparisons, obtained from baseline and follow-up scores, showed an improvement in the depressive and anxiety symptoms of patients who adhered to IFNbeta treatment. Logistic regression analysis indicated that an increase in physical disability and the presence of depressive symptoms at baseline were best predictors for long-term depressive symptoms. CONCLUSIONS: The present results support the absence of emotional worsening in MS patients treated with IFNbeta for a long period of time. Increased disability and the presence of baseline depressive symptoms predicted the presence of depressive symptoms at follow-up.

Percepción de dolor y fibromialgia / Pain perception and fibromyalgia

Introducción. Los factores psicológicos y los procesos de autorregulación, si bien raramente causan dolor, poseen la entidad suficiente para exacerbarlo y contribuir a su mantenimiento, pero la percepción y las creencias asociadas pueden influir en su afrontamiento y en la sensación de intensidad. La percepción del dolor adquiere especial relevancia en el caso de la fibromialgia, ya que la sensibilidad anormal a la presión digital en los llamados tender points constituye el factor principal para su diagnóstico diferencial.Método. Se pretende determinar las diferencias en la percepción del dolor y en las creencias sobre éste que aparecen en un grupo de pacientes con fibromialgia (n = 36), un grupo control con dolor crónico por patología objetivizada del aparato locomotor no inflamatoria (n = 44) y otro grupo control formado por personas sanas (n = 31). La percepción y creencias del dolor se evaluaron mediante versiones españolas de los autoinformes West Haven Yale Multidimensional Questionnaire (WHYWPI) y Pain Percepcions and Beliefs Inventory (PBAPI).Resultados. La diferencia entre pacientes con dolor crónico no se encuentra relacionada con la percepción global del dolor, sino que ésta reside en la mayor percepción del dolor como inhabilitante para realizar actividades cotidianas por parte de los fibromiálgicos. Utilizan estrategias de escape-evitación en su quehacer diario sobre la creencia de que el dolor incapacita y por ello la actividad física debe evitarse.Conclusiones. La percepción y las creencias sobre el dolor pueden ser consideradas relevantes tanto en protocolos de evaluación como en programas de intervención sobre patologías asociadas con dolor crónico

Introduction. Although psychological factors and self-regulation processes rarely cause pain they have enough importance to exacerbate pain and contribute to its maintenance. Nevertheless, pain perception and associated beliefs can influence its confrontation and the sensation of intensity. Pain perception in fibromyalgia acquires special relevance due to an abnormal sensitivity to digital pressure on the so-called «tender points». This constitutes the main factor for its differential diagnosis.Method. The aim of the present study is to determine differences in pain perception and associated beliefs that appear between a group of patients with fibromyalgia (n = 36), a control group with chronic pain with objectified non-inflammatory locomotion apparatus pathology (n = 44) and a control group with healthy subjects (n = 31). Pain perception and beliefs concerning pain were assessed using Spanish versions of the following self-reports: West Haven Yale Multidimensional Questionnaire (WHYWP) and Pain Perceptions and Beliefs Inventory (PBAPI).Results. Results show that the difference between patients with chronic pain is not related to pain global perception, but rather to greater perception of pain as more incapacitating when carrying out every day activities in fibromyalgic patients. In this sense, these people use escape-avoidance strategies in their every day lives believing that pain incapacitates them and therefore that physical activity should be avoided.Conclusions. Measurement of pain perceptions and beliefs could be considered relevant for assessment and for intervention programs on pathologies associated with chronic pain