Background: Developmental effects of exposure to endocrine disruptors can influence adult characters in mammals, but could also have evolutionary consequences. The aim of this study was to simulate an environmental exposure of an experimental population of mice to high amounts of nutritional phytoestrogens and to evaluate parameters of relevance for evolutionary change in the offspring. The effect of a continuous pre-and post-natal exposure to high levels of dietary isoflavones was evaluated on sexual maturity, morphometric parameters and DNA methylation status in mice. Adult mice male/female couples were fed ad libitum either with control diet (standard laboratory chow) or ISF diet (control diet plus a soy isoflavone extract at 2% (w/w) that contained the phytoestrogens genistein and daidzein). In the offspring we measured: i) the onset of vaginal opening (sexual maturation) in females, ii) weight and size in all pups at 7, 14, 21 and 42 days post-natal (dpn) and iii) DNA methylation patterns in skeletal α-actin (Acta1), estrogen receptor-α and c-fos in adults (42 dpn).

Lactation is the most energetically demanding period in the life cycle of female mammals, and its effects on digestive flexibility and the size of internal organs have been extensively studied in laboratory mice and rats since the early 1900s. However, there have been only two studies on this topic for wild rodent species. Here, we analyzed digestive flexibility--that is, changes in gut content, activity of digestive enzymes, and gut morphology--during lactation in the caviomorph rodent Octodon degus. In addition, we evaluated changes in the size of other internal organs and analyzed their relationship with the resting metabolic rate. We found that gut content, the dry masses of digestive chambers, the dry mass of liver, and resting metabolic rate were greater in lactating than in nonbreeding control females. In contrast, fat stores were higher in control subjects. Maltase and aminopeptidase-N specific activity did not change with lactation, and both enzymes had greater activity values in the middle portion of the small intestine. Thus, our data indicate that the previously reported increase in food assimilation that occurs during lactation in O. degus is related to a mass increase in several central organs, leading, in turn, to higher energetic costs. Fat stores may help to mitigate these costs, but, as expected for small animals, to a limited extent. Our study reveals a complex interplay among energy acquisition, storage, and expenditure processes that ultimately determine an organism's fitness.

DNA methylation is one of the epigenetic and hereditary mechanisms regulating genetic expression in mammalian cells. In this review, we propose how certain natural agents, through their dietary consumption, could induce changes in physiological aspects in mammalian mothers, leading to alterations in DNA methylation patterns of the developing fetus and to the emergence of new phenotypes and evolutionary change. Nevertheless, we hypothesize that this process would require (i) certain key periods in the ontogeny of the organism where the environmental stimuli could produce effects, (ii) particular environmental agents as such stimuli, and (iii) that a genomic persistent change be consequently produced in a population. Depending on the persistence of the environmental stimuli and on whether the affected genes are imprinted genes, induced changes in DNA methylation patterns could become persistent. Moreover, some fragments could be more frequently methylated than others over several generations, leading to biased base change and evolutionary consequences.

ABSTRACT.Purpose: To evaluate clinical outcomes of first-line immunomodulatory therapy (IMT) and prednisone alone or late IMT in Vogt-Koyanagi-Harada disease. Methods: Retrospective cohort study of 152 patients with Vogt-KoyanagiHarada disease evaluated in a referral uveitis clinic in Chile from 1985 to 2011. Medical records of these patients were reviewed. Demographic data, clinical evaluation, type of treatment, functional outcomes, glucocorticoid (GC) dose and complications were recorded. Multivariate logistic regression was used to identify prognostic factors of poor response to GC. Results: There were no significant differences between first-line IMT group and prednisone alone/late IMT group in terms of visual acuity (VA) improvement, complications and GC sparing effect. There was a trend for a higher frequency of systemic adverse effects leading to discontinuation of treatment in patients receiving IMT than in those receiving prednisone (14.6% and 6.5%, respectively). The subgroup of patients with poor response to GC who showed functional improvement had a significantly earlier time to IMT initiation than the patients who had no improvement. We identified following prognostic factors of poor response to GC: VA ≤20/200, fundus depigmentation, chronic disease and tinnitus at diagnosis. Patients with a prognostic factor (excluding tinnitus) and VA improvement had an earlier IMT initiation than those who had worse functional outcome. Conclusion: There were no differences in outcomes between first-line IMT and prednisone alone/late IMT in the entire VKH group. However, in a subset of patients, there was a significant better functional outcome with earlier IMT initiation.

No abstract

Non-infectious uveitis (NIU) is a group of disorders characterized by intraocular inflammation at different levels of the eye. NIU is a leading cause of irreversible blindness in working-age population in the developed world. The goal of uveitis treatment is to control inflammation, prevent recurrences, and preserve vision, as well as minimize the adverse effects of medications. Currently, the standard of care for NIU includes the administration of corticosteroids (CS) as first-line agents, but in some cases a more aggressive therapy is required. This includes synthetic immunosuppressants, such as antimetabolites (methotrexate, mycophenolate mofetil, and azathioprine), calcineurinic inhibitors (cyclosporine, tacrolimus), and alkylating agents (cyclophosphamide, chlorambucil). In those patients who become intolerant or refractory to CS and conventional immunosuppressive treatment, biologic agents have arisen as an effective therapy. Among the most evaluated treatments, TNF-a inhibitors, IL blockers, and anti-CD20 therapy have emerged. In this regard, anti-TNF agents (infliximab and adalimumab) have shown the strongest results in terms of favorable outcomes. In this review, we discuss latest evidence concerning to the effectiveness of biologic therapy, and present new therapeutic approaches directed against immune components as potential novel therapies for NIU.

The climatic variability hypothesis (CVH) states that species are geographically more widespread at higher latitudes because individuals have a broader range of physiological tolerance or phenotypic flexibility as latitude and climatic variability increase. However, it remains unclear to what extent climatic variability or latitude, acting on the phenotype, account for any observed geographical gradient in mean range size. In this study, we analyzed the physiological flexibility within the CVH framework by using an intraspecific population experimental approach. We tested for a positive relationship between digestive-tract flexibility (i.e., morphology and enzyme activities) and latitude and climatic and natural diet variability in populations of rufous-collared sparrows (Zonotrichia capensis) captured in desert (27°S), Mediterranean (33°S), and cold-temperate (41°S) sites in Chile. In accordance with the CVH, we observed a positive relationship between the magnitude of digestive-tract flexibility and environmental variability but not latitude. The greatest digestive flexibility was observed in birds at middle latitudes, which experience the most environmental variability (a Mediterranean climate), whereas individuals from the most stable climates (desert and cold-temperate) exhibited little or no digestive-tract flexibility in response to experimental diets. Our findings support the idea that latitudinal gradients in geographical ranges may be strongly affected by the action of regional features, which makes it difficult to find general patterns in the distribution of species.

Understanding physiological traits and ecological conditions that influence a species reliance on metabolic water is critical to creating accurate physiological models that can assess their ability to adapt to environmental perturbations (e.g., drought) that impact water availability. However, relatively few studies have examined variation in the sources of water animals use to maintain water balance, and even fewer have focused on the role of metabolic water. A key reason is methodological limitations. Here, we applied a new method that measures the triple oxygen isotopic composition of a single blood sample to estimate the contribution of metabolic water to the body water pool of three passerine species. This approach relies on Δ'17O, defined as the residual from the tight linear correlation that naturally exists between δ17O and δ18O values. Importantly, Δ'17O is relatively insensitive to key fractionation processes, such as Rayleigh distillation in the water cycle that have hindered previous isotope-based assessments of animal water balance. We evaluated the effects of changes in metabolic rate and water intake on Δ'17O values of captive rufous-collared sparrows (Zonotrichia capensis) and two invertivorous passerine species in the genus Cinclodes from the field. As predicted, colder acclimation temperatures induced increases in metabolic rate, decreases in water intake, and increases in the contribution of metabolic water to the body water pool of Z. capensis, causing a consistent change in Δ'17O. Measurement of Δ'17O also provides an estimate of the δ18O composition of ingested pre-formed (drinking/food) water. Estimated δ18O values of drinking/food water for captive Z. capensis were ~ −11‰, which is consistent with that of tap water in Santiago, Chile. In contrast, δ18O values of drinking/food water ingested by wild-caught Cinclodes were similar to that of seawater, which is consistent with their reliance on marine resources. Our results confirm the utility of this method for quantifying the relative contribution of metabolic versus pre-formed drinking/food water to the body water pool in birds.