Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?

Telomeres are repetitive DNA sequences at the end of chromosomes that protect them from degradation. They have been the focus of intense research because short telomeres would predict accelerated ageing and reduced longevity in vertebrates. Oxidative stress is considered a physiological driver of the telomere shortening and, consequently, short lifespan. Among molecules fighting against oxidative stress, glutathione is involved in many antioxidant pathways. Literature supports that oxidative stress may trigger a compensatory "hormetic" response increasing glutathione levels and telomere length. Here, we tested the link between total glutathione concentration and telomere length in captive birds (zebra finches; Taeniopygia guttata). Total glutathione levels were experimentally decreased during birds' growth using a specific inhibitor of glutathione synthesis (buthionine sulfoximine; BSO). We monitored the birds' reproductive performance in an outdoor aviary during the first month of life, and their longevity for almost 9 years. Among control individuals, erythrocyte glutathione levels during development positively predicted erythrocyte telomere length in adulthood. However, BSO-treated females, but not males, showed longer telomeres than control females in adulthood. This counterintuitive finding suggests that females mounted a compensatory response. Such compensation agrees with precedent findings in the same population where the BSO treatment increased growth and adult body mass in females but not males. BSO did not influence longevity or reproductive output in any sex. However, early glutathione levels and adult telomere length interactively predicted longevity only among control females. Those females with "naturally" low (non-manipulated) glutathione levels at the nestling age but capable of producing longer telomeres in adulthood seem to live longer. The results suggest that the capability to mount a hormetic response triggered by low early glutathione levels can improve fitness via telomere length. Overall, the results may indicate a sex-specific link between glutathione and telomere values. Telomerase activity and sexual steroids (estrogens) are good candidates to explain the sex-biased mechanism underlying the early-life impact of oxidative stress on adult telomere length.

Spanish abstract Los telómeros son secuencias repetitivas de ADN que se encuentran al final de los cromosomas protegiéndolos de la degradación. Los telómeros han sido foco de intensa investigación ya que tener telómeros cortos predice un envejecimiento acelerado y una longevidad reducida en vertebrados. El estrés oxidativo se considera causante del acortamiento de los telómeros y, consecuentemente, una corta esperanza de vida. Entre las moléculas que luchan contra el estrés oxidativo, el glutatión está relacionado con numerosas vías metabólicas de otros antioxidantes. La literatura defiende que el estrés oxidativo podría desencadenar una respuesta hormética compensatoria, aumentando los niveles de glutatión y la longitud de los telómeros. En este trabajo testamos la relación entre los niveles de glutatión y la longitud de los telómeros en aves en condiciones de cautividad (diamantes mandarines; Taeniopygia guttata). Los niveles de glutatión fueron reducidos experimentalmente durante el desarrollo de las aves usando un inhibidor específico de la síntesis de glutatión (Buthionina sufolximina; BSO). El desempeño reproductivo de estas aves fue monitoreado en un aviario exterior durante los primeros meses de vida y la longevidad durante casi nueve años. Entre los individuos controles, los niveles de glutatión durante el desarrollo predijeron positivamente la longitud de los telómeros a edad adulta. Sin embargo, las hembras tratadas con BSO, pero no los machos, mostraron telómeros más largos a edad adulta que las hembras controles. Este hallazgo aparentemente contradictorio sugiere que las hembras desarrollaron una respuesta compensatoria. Tal compensación concuerda con los hallazgos anteriores obtenidos en la misma población: las hembras tratadas con BSO vieron aumentado su peso corporal a edad adulta, resultado no encontrado entre los machos. El tratamiento con BSO no afectó la longevidad o el desempeño reproductivo de ningún sexo. Sin embargo, los niveles de glutatión durante el desarrollo y la longitud de los telómeros a edad adulta predijeron interactivamente la longevidad de las hembras controles. Aquellas hembras con niveles bajos "naturales" (no manipulados) de glutatión cuando eran pollos pero que pudieron producir telómeros más largos a edad adulta vivieron más. Este resultado sugiere que la capacidad de desarrollar una respuesta hormética desencadenada por niveles bajos de glutatión durante el desarrollo puede mejorar la eficacia biológica a través de la longitud de los telómeros. De manera general, los resultados indicarían una relación específica del sexo entre los valores de glutatión y de telómeros. La actividad de la enzima telomerasa y los esteroides sexuales (estrógenos) son buenos candidatos para explicar este mecanismo dependiente del sexo que impulsa el impacto del estrés oxidativo sufrido durante el desarrollo en la longitud de los telómeros de adultos.

An age-related decline in the expression of a red carotenoid-based ornament in wild birds.

The past decades have provided valuable information on how animals age in the wild. However, examples of male reproductive senescence are scarce. In particular, few studies have described an age-related decline in the expression of conspicuous traits influencing mating success. Red ornaments could be good candidates to detect this decline because their expression may depend on the availability of pigments (carotenoids) related to oxidative stress, the latter frequently linked to senescence. Furthermore, it has been argued that efficient mitochondrial metabolism is key to express red carotenoid-based ornaments, and mitochondrial dysfunction is usually associated with senescence. We studied the age-linked expression of a red carotenoid-based trait: the yellow-to-red plumage coloration of male common crossbills (Loxia curvirostra). This coloration has recently been experimentally related to mitochondrial function. Here, we analyzed longitudinal plumage coloration data obtained throughout 28 years in free-living birds. We detected an initial increase in redness during the first 2 years of life and a subsequent decline. The relationship between color and age was unrelated to within-individual body mass variability. As far as we know, this is the first demonstration of an age-related ketocarotenoid-based color decrease detected by simultaneously testing within- and between-individual variability in wild animals.

Análisis de un programa de teleoftalmología para el cribado de retinopatía diabética en área rural tras cinco años / Five-year experience of tele-ophthalmology for diabetic retinopathy screening in a rural population

OBJETIVO: Estudiar la prevalencia de retinopatía diabética (RD) y los factores de riesgo asociados en la población incluida en un programa de teleoftalmología en área rural. Evaluar la capacidad diagnóstica de RD de los médicos de atención primaria (MAP) y su correcta coordinación con los oftalmólogos, cuantificando el ahorro generado. MATERIAL Y MÉTODOS: Estudio observacional transversal de una muestra aleatoria de 394 pacientes incluidos en el programa de teleoftalmología desde enero de 2010 a enero de 2015. Analizamos características clínicas, hallazgos de RD en las retinografías y la correcta derivación de imágenes por los MAP al servicio de oftalmología según los criterios establecidos: RD moderada o severa, baja agudeza visual (AV), mala calidad de imagen y presión intraocular (PIO) > 22 mmHg. Análisis estadístico con SPSS. Pruebas t de Student y χ 2. RESULTADOS: La prevalencia de RD fue del 12,1%. Los pacientes con hemoglobina glucosilada > 7,68% o tratados con combinación de antidiabéticos orales e insulina presentaron mayor riesgo de RD (p < 0,05). El 43,3% de los pacientes derivados correctamente a oftalmología presentaban retinopatía moderada o severa. Los pacientes no derivados a oftalmología de forma correcta pasaron de un 91,7% en 2010 a un 98,6% en 2014. Estimamos un ahorro global de 152.550,45€. CONCLUSIONES: El programa de teleoftalmología resulta útil como cribado de RD. Los MAP son capaces de discriminar los pacientes que requieren valoración oftalmológica, evitando consultas presenciales y generando ahorro

OBJECTIVE: To identify the prevalence and risk factors of diabetic retinopathy (DR) among rural inhabitants included in a tele-ophthalmology program. To analyse diagnostic accuracy among primary care physicians, concordance with ophthalmologists, and financial savings. MATERIAL AND METHODS: An observational randomised study was conducted on 394 patients included in a tele-ophthalmology program (from January 2010 to January 2015). An analysis was performed on the clinical characteristics, DR findings in retinography images, and correspondence between the request for a second interpretation by an ophthalmologist, and previously established criteria for it: presence of moderate to severe DR, vision loss, poor image quality and/or intraocular pressure > 22 mmHg. Statistical analysis was performed using the SPSS program (Student t and χ 2 tests). RESULTS: DR prevalence was 12.1%. Patients with glycosylated haemoglobin values > 7.68% or those treated with a combination of insulin and oral antidiabetic drugs showed a higher risk of DR (P < .05). 43.3% of patients correctly referred to ophthalmologists showed moderate to severe DR. Unnecessary referrals to specialists were improved from 91.7% in 2010 to 98.6% in 2014. It is estimated that the program has made a total saving of €152,550.45. CONCLUSIONS: Tele-ophthalmology programs are a useful tool in DR screening. Primary care physicians are able to distinguish patients who need specialist care, avoiding unnecessary referrals to ophthalmologists, and saving costs

The oxidative cost of reproduction depends on early development oxidative stress and sex in a bird species.

In the early 2000s, a new component of the cost of reproduction was proposed: oxidative stress. Since then the oxidative cost of reproduction hypothesis has, however, received mixed support. Different arguments have been provided to explain this. Among them, the lack of a life-history perspective on most experimental tests was suggested. We manipulated the levels of a key intracellular antioxidant (glutathione) in captive zebra finches (Taeniopygia guttata) during a short period of early life and subsequently tested the oxidative cost of reproduction. Birds were allowed to mate freely in an outdoor aviary for several months. We repeatedly enlarged or reduced their broods to increase or reduce, respectively, breeding effort. Birds whose glutathione levels were reduced during growth showed higher erythrocyte resistance to free radical-induced haemolysis when forced to rear enlarged broods. This supports the hypothesis predicting the occurrence of developing programmes matching early and adult environmental conditions to improve fitness. Moreover, adult males rearing enlarged broods endured higher plasma levels of lipid oxidative damage than control males, whereas adult females showed the opposite trend. As most previous studies reporting non-significant or opposite results used females only, we also discuss some sex-related particularities that may contribute to explain unexpected results.

Usefulness of surgical complexity classification index in cataract surgery process. / Utilidad del índice de complejidad quirúrgica en el proceso de cirugía de catarata.

OBJECTIVE: To evaluate the usefulness of surgical complexity classification index (SCCI) to predict the degree of surgical difficulty in cataract surgery. MATERIAL AND METHODS: This retrospective study includes data collected between January 2013 and December 2014 from patients who underwent cataract extraction by phacoemulsification at our hospital. A sample size of 159 patients was obtained by simple random sampling (P=.5, 10% accuracy, 95% confidence). The main variables were: recording and value of SCCI in electronic medical record (EMR), presence of exfoliation syndrome (XFS), criteria for inclusion in surgical waiting list (SWL), and functional results. SCCI was classified into 7 categories (range: 1-4) according to predictors of technical difficulty, which was indirectly estimated in terms of surgical time (ST). All statistical analyses were performed using SPSS v15.0 statistical software. RESULTS: Prevalence of XFS was 18.2% (95%CI: 11.9-24.5). In terms of quality indicators in the cataract surgery process, 96.8% of patients met at least one of the criteria to be included in SWL, and 98.1% gained ≥2 Snellen lines. The SCCI was recorded in EMR of 98.1% patients, and it was grouped for study into 2 categories: High and low surgical complexity. Statistically significant differences in the distribution of ST were found depending on the assigned SCCI (P<.005) and the presence of XFS (P<.005). CONCLUSIONS: The SCCI enables to estimate the degree of surgical complexity in terms of ST in cataract surgery, which is especially useful in those areas with high prevalence of XFS, because of the higher theoretical risk of surgical complications.

Five-year experience of tele-ophthalmology for diabetic retinopathy screening in a rural population. / Análisis de un programa de teleoftalmología para el cribado de retinopatía diabética en área rural tras cinco años.

OBJECTIVE: To identify the prevalence and risk factors of diabetic retinopathy (DR) among rural inhabitants included in a tele-ophthalmology program. To analyse diagnostic accuracy among primary care physicians, concordance with ophthalmologists, and financial savings. MATERIAL AND METHODS: An observational randomised study was conducted on 394 patients included in a tele-ophthalmology program (from January 2010 to January 2015). An analysis was performed on the clinical characteristics, DR findings in retinography images, and correspondence between the request for a second interpretation by an ophthalmologist, and previously established criteria for it: presence of moderate to severe DR, vision loss, poor image quality and/or intraocular pressure >22mmHg. Statistical analysis was performed using the SPSS program (Student t and χ(2) tests). RESULTS: DR prevalence was 12.1%. Patients with glycosylated haemoglobin values >7.68% or those treated with a combination of insulin and oral antidiabetic drugs showed a higher risk of DR (P<.05). 43.3% of patients correctly referred to ophthalmologists showed moderate to severe DR. Unnecessary referrals to specialists were improved from 91.7% in 2010 to 98.6% in 2014. It is estimated that the program has made a total saving of €152,550.45. CONCLUSIONS: Tele-ophthalmology programs are a useful tool in DR screening. Primary care physicians are able to distinguish patients who need specialist care, avoiding unnecessary referrals to ophthalmologists, and saving costs.

Factores psicológicos favorecedores de la abstinencia alcohólica en un grupo de alcohólicos rehabilitados / Positive psychological factors in the alcoholic abstinence on a group of rehabilitated alcoholic individuales

Objetivos: Caracterizar los factores psicológicos favorecedores de la abstinencia alcohólica en un grupo de abstinentes alcohólicos, los específicos, caracterizar los mecanismos autorreguladores de la personalidad de los abstinentes (sistema motivacional, autovaloración y dimensión temporal), e identificar las diferencias entre abstinentes y consumidores con relación a las variables de estudio. Métodos: investigación cualitativa-descriptiva de corte transversal y con diseño no experimental. Se emplearon la Entrevista, el Cuestionario de Factores, así como los tests psicológicos Registro de la Actividad y Métodos Directo e Indirecto y la Escala autovalorativa Dembo-Rubinstein. Resultados: Se evidenciaron diferencias en ambos grupos con respecto a las categorías de estudio y se observó un predominio de factores favorecedores de la abstinencia alcohólica en los abstinentes, mientras que en los consumidores predominaron los factores de riesgo de la abstinencia.Conclusiones: Los mecanismos autorreguladores de la personalidad en abstinentes alcohólicos se caracterizan por una motivación por el cambio muy buena, una autovaloración, perspectiva temporal y dimensión temporal adecuadas.Los factores psicológicos favorecedores de la abstinencia alcohólica en los alcohólicos abstinentes son: optimismo ante situaciones difíciles, solidaridad con otros alcohólicos, asistencia regular a grupos de Alcohólicos Anónimos (AA) y/o psicoterapéuticos, autovaloración positiva hacia el autocontrol emocional, la dimensión temporal y empleo útil del tiempo, conciencia de enfermedad, confianza en la rehabilitación, no creen poder consumir alcohol con control, creen en Dios o en poder superior, desarrollan valores morales, estables en pareja, laboral, buen humor, con planes futuros, entre otros(AU)

Objectives: to characterize the specific positive psychological factors in the alcoholic abstinence on a group of rehabilitated alcoholic individuals; to characterize the personality self regulators mechanisms of the abstinent individuals (motivational system, self assessment and temporal dimension); to identify the difference between abstinent individual and consumers according to the study variable. Methods: a non experimental design, transversal and descriptive- qualitative research was carried out. The questionnaire of Factors, Interview and the psychological tests Register of Activities and Direct and Indirect Methods and Dembo Rubenstein Self –Assessment Scale were used.Results: there were found differences between both groups according to the categories of study and a prevalence of positive factors in the alcoholic abstinence on the group of alcoholic individual, meanwhile on the group of consumers the risks of the abstinence prevailed. Conclusions: the personality self regulators mechanisms of the abstinent individuals are: optimism before complex situations, positive self assessment towards emotional self control, temporal dimension, useful use of time, awareness of the disease, trust on rehabilitation therapy, they do not believe that they are able to consume alcohol with control, they believe in God or in a Superior Divinity Power, they develop moral principles, they become stable with their couple and also with their work´s duties, they become liable with other alcoholic individuals, they are able to make plans for the future and to have a good disposition, they also have a regular participation to Anonym Alcoholic Groups or to Psychotherapy Groups among other characteristics(AU)

Testosterone-mediated trade-offs in the old age: a new approach to the immunocompetence handicap and carotenoid-based sexual signalling.

The immunocompetence handicap hypothesis proposes that testosterone mediates a trade-off between sexual signalling and immunocompetence in males. Such a trade-off could favour the reliability of sexual signals on the basis that testosterone required for signal expression also promotes immunosuppression. However, the immunosuppressive activity of testosterone has not been convincingly demonstrated. We propose that the optimal solution to the testosterone-mediated trade-off should change with age, explaining ambiguous results in the past. Testosterone and ageing would promote two simultaneous immunosuppressive challenges unaffordable for low-quality males. Oxidative stress, as intimately related to ageing and immunosenescence, could contribute to enhance signal reliability. In this context, traits coloured by carotenoids (yellow-red traits) could play a crucial role due to the immunostimulatory and antioxidant properties of these pigments. Here, old and middle-aged male red-legged partridges were treated with testosterone or manipulated as controls. In the presence of high-testosterone levels, middle-aged males increased both circulating carotenoid levels and colour expression, whereas their cell-mediated immunity was not significantly altered. However, in old males, neither circulating carotenoids nor sexual signalling increased when treated with testosterone, but immunosuppression was detected. The link between testosterone and carotenoids could favour the reliability of sexual signals throughout the life.

The oxidation handicap hypothesis and the carotenoid allocation trade-off.

The oxidation handicap hypothesis proposes that testosterone mediates the trade-off between the expression of secondary sexual traits and the fight against free radicals. Coloured traits controlled by testosterone can be produced by carotenoid pigments (yellow-orange-red traits), but carotenoids also help to quench free radicals. Recently, it has been shown that testosterone increases the amount of circulating carotenoids in birds. Here, a testosterone-mediated trade-off in the carotenoid allocation between colour expression and the fight against oxidative stress is proposed. Male red-legged partridges were treated with testosterone, anti-androgens or manipulated as controls. Testosterone-treated males maintained the highest circulating carotenoid levels, but showed the palest red traits and no evidence of oxidative damage. Increased levels of a key intracellular antioxidant (i.e. glutathione) indicated that an oxidative challenge was in fact induced but controlled. The trade-off was apparently solved by reducing redness, allowing increased carotenoid availability, which could have contributed to buffer oxidative stress.

Energetic reserves, leptin and testosterone: a refinement of the immunocompetence handicap hypothesis.

The immunocompetence handicap hypothesis (ICHH) assumes that testosterone (T), required for the expression of sexual traits, can also incur a cost due to its immunosuppressive properties. However, T-dependent immunosuppression could also arise as an indirect consequence of energy reallocation from the immune system to other metabolic demands. Leptin is mostly produced in lipogenic tissues and its circulating level is positively correlated with the amount of lipid reserves. Leptin also has an important role as immunoenhancer and we suggest that this hormone could play a role as a mediator of the immunosuppressive effect of testosterone. In particular, we propose that only the individuals able to maintain large lipid reserves (with high leptin levels), while sustaining high testosterone levels, might be able to develop sexual displays without an impairment of their immune defences. Here, we tested one of the assumptions underlying this extension of the ICHH: leptin administration should attenuate testosterone-induced immunosuppression. T-implanted and control male zebra finches (Taeniopygia guttata) received daily injections of leptin or phosphate buffered saline. T-implants initially depressed the phytohaemagglutinin-induced immune response. However, T-birds injected with leptin enhanced their immune response to the level of control birds. These results open a new perspective on the study of the ICHH.

A biochemical study of fasting, subfeeding, and recovery processes in yellow-legged gulls.

An investigation of the effects of fasting, subfeeding, and refeeding on plasma biochemistry was carried out on 22 captive yellow-legged gulls Larus cachinnans Pallas. These birds showed the same fasting endurance model described in other species, but with an important decrease in glucose plasma concentration and very great differences between individuals when reaching the deterioration limit, suggesting a moderate physiological adaptation to long periods of fasting. A different model was proposed in subfed gulls in relation to fasted gulls, based on lipid and protein use, which could be reflected by changes in nitrogen wastes and triglyceride levels in this experiment. Thus, the subfed gulls might use protein directly from the diet as an energy source, thereby reducing the use of fat stores. The gulls quickly recovered body mass during the refeeding period, but while some plasma substances quickly reached their initial values, others showed many changes before the end of the experiment, which could reflect a process of metabolic restabilization. These results contribute to a better knowledge of fasting, subfeeding, and refeeding processes in birds and can be added to a recent study about fasting in gulls.

[Traumatic maculopathies]. / Maculopatías traumáticas.

PURPOSE/METHODS: We reviewed all patients seen urgently on our Hospital and we studied those that present contusive pathology of the anterior pole with macular repercusion. RESULTS/CONCLUSIONS: Post-traumatic maculopathies are usually produced by contusion, namely: rupture of the choroid, chorioretinitis sclopetaria, postraumatic macular hole, commotio retinae (Berlin's oedema) and Purtscher's retinopathy was reported. With the presentation of these clinical cases, some of which are very typical, we aim to show the functional sequelae some patients suffer.

Maculopatías traumáticas / Traumatic maculopathies

Objetivo/Método: Revisamos todos los pacientes vistos de urgencia en nuestro Hospital y estudiamos aquellos que presentan patología contusiva del polo posterior con repercusión macular. Resultados/Conclusiones: Las contusiones originan frecuentemente maculopatías postraumáticas; citaremos: la ruptura coroidea, la coriorretinitis esclopetaria, el agujero macular, el edema de Berlin y la retinopatía de Purtscher. Con la presentación de estos casos clínicos, algunos muy típicos, pretendemos demostrar las secuelas funcionales que sufren algunos pacientes (AU)