In contrast, plaque brachytherapy places the source on the sclera

In contrast, plaque brachytherapy places the source on the sclera beneath (adjacent to) the tumor. Thus, in the treatment of posterior choroidal melanomas, radiation must travel through the sclera before entering the tumor and through the eye before exiting through normal anterior ocular tissues (26). Primarily because of dose gradient and side-scatter effects, plaque brachytherapy delivers

comparatively more radiation to subjacent sclera and adjacent ocular structures (13). The ABS-OOTF recognizes (Level 1 Consensus) that in the treatment of posterior uveal melanomas, there is less resultant radiobiologic effect on normal anterior ocular structures using low-energy (103Pd, 125I) plaque brachytherapy compared with proton beam. This relative dose sparing may explain why clinical studies have Selleck INCB024360 revealed more anterior segment complications and secondary enucleations Natural Product Library after charged particle therapy [107], [108], [110], [111], [112], [113] and [114]. External beam radiation techniques (proton, helium ion, gamma knife, and stereotactic radiosurgery) are also complicated

by mobile target volume (eye movement). Since eye plaques are sewn to the eye wall beneath their target volume, when the eye moves so does the plaque. In contrast, when a target volume is externally created to extend within the eye (all EBRT techniques), mobility of the eye makes intraocular dose deposition less predictable. This is why during proton therapy, eye movements must be constantly monitored and the patient reminded (as needed) to fixate on a reference target. This is because eye movements cause misapplication of protons within the eye. In addition, should larger tumor-free safety margins become necessary, more normal tissues (anterior and posterior) fall within the cylindrical target volume. In addition, proton beam facilities are vastly more expensive (Table 4) [115] and [116]. The ABS-OOTF survey indicates that proton beam has been used as an alternative to enucleation for tumors considered unsuitable for brachytherapy. This Oxymatrine includes tumors

that touch or surround the optic disc, for very large tumors and where 125I and 103Pd plaques are not available. In addition, a novel strategy tries to prevent secondary inflammation; “vitritis” or “toxic tumor syndrome” has been described after brachytherapy for large choroidal melanoma. Here, large uveal melanomas are first treated with proton beam and then removed by internal resection (102). There are only a few centers using this technique (ABS-OOTF Level 3 Consensus). Reporting the results of treatment is particularly challenging. Consider that when multiple centers use the same radionuclides source, they often differ in plaque construction, dosimetry, doses, and dose rate. Furthermore, until acceptance of the AJCC staging system, there existed no universal method to report the size of uveal melanomas.

Moreover, the GGE biplot provides greater insight, as it illustra

Moreover, the GGE biplot provides greater insight, as it illustrates the relationship between the genotype and its GE interaction [8]. However, the GGE biplot results need to be validated with the original data. According to the original data, genotypes G4 and G6 had respectively the highest and lowest mean yield performances across environments, an inference supported graphically by fitting the GGE model to the original data (Fig. 4 and Table 1), suggesting that the GGE biplot results are in agreement with the original yield data. These results are in accord Staurosporine mw with those of other studies [16] and [17] that found agreement between GGE biplot results and the

original yield data. Phenotypic yield stability is a trait of special interest for plant breeders and farmers. This trait can be quantified if genotypes are evaluated in different environments [30]. No correlation was found between yield ranks and stability ranks that were based on measuring GE interaction, including AMMI distance in the AMMI model; stability index in the GGE biplot; S2di MK-2206 molecular weight in the JRA; and σ2 in the YSi statistic, indicating that these stability indices describe static stability and accordingly could be used if selection is to be based primarily on stability. This conclusion is in agreement with other reports on cereal crops for which stability indices based on measuring GE effects are not correlated with mean yield in bread

wheat, durum wheat and barley [31]. It is also supported by other reports

[32], [33], [34], [35] and [36]. Helms [32] found that the correlations of oat yield with σ2 and S2di were poor. Jalaluddin and Harrison [33] reported no correlation of wheat grain yield with σ2 or S2di. Sneller et al. [35] also found no relationship of soybean yield with the statistics AMMI, σ2, and S2di. Many statistical methods have been developed to analyze data from MET to gain a better understanding and interpretation of observed GE interaction patterns, with the aim of identifying outstanding new cultivars with high stability in crop breeding programs. A worthwhile discussion of many of these methods and their efficiency in identifying superior Carbachol genotypes in MET data can be found in reviews [10], [11], [12], [13], [16], [17] and [18]. Fan et al. [14] and Mohammadi et al. [15] reported high rank correlations between GGE and YSi and concluded that YSi should be useful in selecting superior genotypes in the absence of GGE biplot software. Baxevanos et al. [37] also reported a high correlation between YSi and GGE distance. Goyal et al. [17] reported some agreement between JRA and GGE biplot methods in identifying stable genotypes with high yield performance. According to Goyal et al. [17], S2di and GGE biplot models were not in general agreement in identifying high-yielding and stable genotypes, a conclusion differing from that of Alwala et al. [16].

Kinases and their inhibitors, phosphatases, are key regulators of

Kinases and their inhibitors, phosphatases, are key regulators of several cellular functions, and their appropriate learn more activity is required for the cellular homeostasis; on the contrary, their aberrant activation is crucial in driving oncogenesis. The concept that cancer-mutated kinases molecularly mark “druggable” targets has resulted in intensive efforts to

survey the kinome across a wide spectrum of human tumor types for mutations and to the development of several targeted inhibitors [3]. On this basis, we reasoned that, as in malignant proliferations, TK activation could play a role in IPF, although few data about molecular mechanisms involved in disease onset and progression are available. A confirmation of a role of TK activation

pathways in IPF would make them actionable with specific molecules, in a similar fashion to cancer-targeted therapy. We selected and analyzed 17 consecutive IPF samples derived from medical thoracoscopy cases from a cohort of patients aged ≥ 18 years who referred to our Institution for diagnosis and therapy. In all patients with IPF, the histopathologic examination revealed all of the major features of usual interstitial selleckchem pneumonia (UIP ) [temporally and architecturally heterogeneous interstitial fibrosis, with fibroblast foci (FF), microscopic honeycombing, subpleural and periseptal accentuation, and absence of histologic features specific of other diseases], which is a prerequisite for the diagnosis

of IPF. The final diagnosis of IPF was based on the diagnostic criteria of the American Thoracic Society/European Respiratory Society Consensus Classification System after evaluation of all clinical, laboratory, and instrumental data [4] and [5]. We also checked 40 non–small cell lung cancer (NSCLC) samples [20 adenocarcinoma (ADC) and 20 from squamous cell cancer] obtained through endobronchial, transbronchial, or transthoracic biopsy. Clinical characteristics of cases analyzed are reported in Table 1. Orotidine 5′-phosphate decarboxylase Immunohistochemical (IHC) analysis was performed with antibodies against phospho–mammalian target of rapamycin (P-mTOR) (1:100, rabbit monoclonal, clone 49 F9; Cell Signaling Technology, Danvers, MA), phosphatase and tensin homolog (PTEN) (1:400, mouse monoclonal, clone 6H2.1; Dako, Cernusco sul Naviglio, MI, Italy), phospho-MET (P-met) (1:100, rabbit monoclonal, clone D26; Cell Signaling Technology), and phospho-ezrin/radixin/moesin (P-ERM) (1:300, rabbit monoclonal, clone 41A3; Cell Signaling Technology) on 4-μm–thick paraffin sections. Tissue sections were incubated at 60°C overnight and then deparaffinized. The slides underwent 40 minutes of heat-mediated antigen retrieval in citrate buffer (pH 6) and incubated for 20 minutes with ready-to-use normal horse blocking serum. Primary antibody was incubated overnight at + 4°C.

These hypotheses will be demonstrated below In the Southern Ocea

These hypotheses will be demonstrated below. In the Southern Ocean, CM5_piStart PLX4032 research buy is generally too cold around 50°S and too warm south of 60°S in the surface as compared to observations (Fig. 8 top left). The warm surface anomalies do not extend at depth though, where CM5_piStart is generally too cold over

the whole water column (Fig. 9 top left). This surface warm bias remains relatively unchanged in CM5_RETRO. Yet it extends down to almost 1000 m as well as along the oceanic floor (except for weak anomalies of the opposite sign between 50 m and 100 m, suggesting a modification of the thermocline). This is consistent with the forced simulations (compare F5_CMIP5 and F1_CMIP3, Fig. 2). The suite of sensitivity experiments in forced mode suggests that this effect is due to the implementation of the partial steps (F2). Bottom waters along the Antarctic continental shelf are colder in CM5_piStart as compared to CM5_RETRO. This is indicative of an intensified AABW formation, in agreement with forced

simulations, and confirmed by deeper mixed layers (not shown) and meridional streamfunctions (below). Furthermore, along the Antarctic continent, surface water masses are saltier Pexidartinib solubility dmso in CM5_piStart, while they are fresher north of 50°S (Fig. 9 bottom right). Fig 10 shows that these salinity anomalies in the Southern Hemisphere are responsible for an increase of the density gradient across Low-density-lipoprotein receptor kinase the Southern Ocean (80°S–50°S) in CM5_piStart by roughly 15% as compared to CM5_RETRO. This consistent with intensified ACC in CM5_piStart, as described below. Regarding the tropical regions, Fig. 8 (bottom) shows that surface waters are colder by up to 1 °C and saltier by more than 1.5 psu in CM5_piStart as compared to CM5_RETRO in the southern part of the Indonesian Archipelago

(IA). This results from the implementation of tidal mixing, consistent with coupled simulations from Koch-Larrouy et al. (2009). Further north, offshore of southeastern Asia, CM5_piStart displays a strong fresh anomaly compared to observations while this anomaly was much weaker in CM5_RETRO. This difference between the two simulations can be partly tracked down to changes in atmospheric freshwater flux, as shown in Fig. 12, with larger precipitation into the ocean (blue colour) in CM5_piStart along 5°N and weaker along the Equator and 5°S in the Indian Ocean. These changes are the signature of a northward shift of the ITCZ, and induce the SSS anomalies seen in Fig. 8 (bottom right). Note that from Fig. 12, atmospheric freshwater changes are also very strong in the tropical Atlantic, similarly characterised by a northward shift of the mean ITCZ position (around 10°N). Stronger precipitation are also found along 10°S.

Each

buck was collected twice a week Immediately after c

Each

buck was collected twice a week. Immediately after collection, the ejaculates were maintained immersed in a warm Sirolimus water bath at 37 °C. Semen assessment was performed within approximately 15 min, and only those semen samples with at least 80% sperm progressive motility were selected for freezing. A total of 21 ejaculates (seven per animal) were used in this experiment. Color, aspect and volume were evaluated in fresh semen. Microscopic criteria such as sperm progressive motility (%) and mass activity (0–5 scale) were performed subjectively by light microscopy (Nikon, Eclipse E200, Tokyo, Japan) under 100× magnification. Structural integrity of plasma membrane was established by analyzing a slide stained with Bromo-phenol Blue under light microscopy (400×), counting 200 cells per slide. Following initial assessment, a 10 μL semen aliquot was diluted in 2 mL of buffered formalin (10%) and sperm concentration (sperm ×106 mL−1) was determined using

a Neubauer counting chamber. For sperm morphology evaluation, 200 sperm cells from random fields in Bengal Rose smears were analyzed by light microscopy, under PTC124 1000× magnification. Total sperm defects were counted in 200 cells, following classification as primary or secondary [23]. For the evaluation of sperm membrane integrity, a hypo-osmotic swelling test (HOST) was performed immediately Phosphoglycerate kinase after the semen collection, using a citric acid and fructose hypo-osmotic solution (100 mOsm/L). A total of 200 spermatozoa were counted using a phase-contrast microscope at 400× magnification, and spermatozoa presenting swollen coiled tails were considered as presenting a functional sperm membrane [13]. An extender consisting of 3.028 g Tris–hydroxymethyl-aminomethane, 1.78 g monohydrated citric acid and 1.25 g d-fructose, dissolved in 100 mL of distilled water, was used [33].

The osmosis of this solution was 295 mOsm/L and the pH 6.6. Two and a half percent of this solution was subsequently replaced by egg-yolk. Semen was initially divided in two aliquots and extended in Tris–egg yolk at room temperature (32 °C). Samples were kept in an isothermal box and transported to the laboratory. After 40 min, temperature into the isothermal box reached 15 °C (−0.30 °C/min), and the samples were transferred to a refrigerator for a further 30 min, where it reached 4 °C at −0.37 °C/min. Progressive motility was evaluated yet at 4 °C. After cooling, one semen aliquot was added to Tris–egg yolk plus glycerol in a final concentration of 6%, and the other was added to Tris–egg yolk plus DMF in a final concentration of 6%. Final dilution resulted in a sperm concentration of 150 × 106 sperm/mL. Each sample was packed into previously marked 0.

The ability of Ts-DF venom to induce more potent effects on secre

The ability of Ts-DF venom to induce more potent effects on secretory discharge as well as on vesicular transport mechanisms in the exocrine pancreas than Ts-MG venom needs to be verified. In conclusion, the observation of a smaller diversity of supposedly NaScTx in the Ts-DF venom may explain the lower toxicity of this venom when compared to Ts-MG. Also, the inability to induce acute pulmonary edema in rats could explain the absence of severe clinical symptoms and death in patients stung by scorpions

in the DF. Given the above Trametinib and considering the LD50 determined here, it can be inferred that the maximum amount of venom that could be inoculated by T. serrulatus from the DF during a sting would not be sufficient to induce the onset of symptoms of severe poisoning in humans, while the T. serrulatus scorpion releases about 450 μg of venom after electrical stimulation (data not shown). However it is noteworthy that scorpionism in the DF cannot be neglected because of the increased presence of T. serrulatus in this region. This can over time trigger the emergence of a public health problem. Financial support: FAPDF, CNPq

(306524/2012-0 and 564223/2010-7 to EFS and 308929/2011-0 to AMCP), PPG BioMol-UnB, CAPES, FAPEMIG and MCT-FINEP. Fagner Neves Oliveira (579427/2008-0) and Jimmy A. Guerrero Vargas (553137/2007-7) also received fellowship from CNPq. The authors greatly acknowledge Natiela B. de Oliveira, Caroline B. F. Mourão, Braulio S. S. Filho and Lucélia G. for Vieira for technical assistance. Jimmy A. Guerrero-Vargas is member of Grupo de Investigaciones Herpetologícas y Toxinológicas from Universidad del Cauca, Colombia. “
“Spiders Ruxolitinib clinical trial of the genus Loxosceles, commonly known as brown spiders, have a worldwide distribution with more than 100 species present in Europe, Africa, Oceania, Asia, North America, Central America, and South America ( Vetter, 2008). In Brazil, especially in the southern and southeastern regions, the predominant species are Loxosceles intermedia, Loxosceles gaucho, and Loxosceles laeta ( Pauli et al., 2006). Over

the last decade, research studies, motivated by the growing number of envenomation cases have reported that the spider distribution has become heterogeneous and includes urban areas ( da Silva et al., 2004 and Hogan et al., 2004; Chatzaki et al., 2012; Tambourgi et al., 2010). Envenomation cases in humans are characterized by two clinical manifestations: cutaneous and systemic loxoscelism. The former is characterized by the formation of a dermonecrotic lesion. The second, which is also known as cutaneous-visceral loxoscelism, presents clinical manifestations that may cause, in some situations, disseminated intravascular coagulation, acute renal failure and in rare cases, generalized rash and death (Futrell, 1992 and Swanson and Vetter, 2005). Several protocols for the treatment of Loxosceles envenomation have been proposed and tested.

The phytoplankton absorption coefficient aph(λ) was then obtained

The phytoplankton absorption coefficient aph(λ) was then obtained as the difference between ap(λ) and ad(λ). Veliparib manufacturer We also measured the absorption coefficient of coloured dissolved organic matter aCDOM (λ) [m−1] using a Unicam UV4-100 spectrophotometer. These measurements were made in 5 cm cuvettes on samples

filtered through a 0.2 μm acetate filter and relative to pure water (deionized and particle-free). The values of aCDOM(λ) were calculated by multiplying the baseline-corrected optical densities ODCDOM(λ) by ln(10) and dividing by the pathlength of 0.05 m. Assuming that aCDOM(λ) is negligible at wavelengths roughly above 680 nm, any measured offset was subtracted to obtain the final aCDOM(λ). The scattering coefficients of particles bp(λ) [m−1] were calculated as the difference between the spectral attenuation and absorption coefficients by non-water constituents (dissolved

and particulate) – cn(λ) and an(λ) respectively. The latter were measured in situ in the near-surface layer (ca 1.5 m depth) using a spectral absorption-attenuation meter (WET Labs ac-9) at nine wavelengths (412, 440, 488, 510, 532, 555, 650, 676, 715 nm) and a 25 cm pathlength. Corrections for in situ temperature and salinity effects on the optical properties of water were applied according to Pegau et buy NVP-BEZ235 al. (1997). A correction for the incomplete recovery of the scattered light in the absorption tube of the ac-9 instrument (the so-called proportional method) was used according to Zaneveld et al. (1994). The backscattering coefficients of particles

bbp(λ) [m−1] were estimated from in situ measurements performed in the near-surface layer (ca 1.5 m depth) using a spectral backscattering meter (HOBI Labs Hydroscat-4) at four wavelengths (420, 488, 550 and 620 nm). The raw data from the instrument, i.e. values of volume scattering function Nintedanib (BIBF 1120) at an angle of 140°, β(140) were used for estimating bbp according to the method described in Maffione & Dana (1997) and Dana & Maffione (2002). A correction for the incomplete recovery of backscattered light in highly attenuating waters (the so-called sigma-correction) was applied in accordance with the instrument User’s Manual ( HOBI Labs 2008) using data on absorption and attenuation coefficients measured with the ac-9 instrument. The volume scattering functions of particles for a light wavelength of 532 nm, βp,532(θ) [m−1 sr−1], were also measured in situ in the near-surface layer of seawater for a portion of our samples (collected between April 2008 and September 2009). This was done with a WET Labs ECO volume scattering function meter at angles of 100, 125 and 150°. The raw data measured with this instrument were corrected for the dark counts of the detector (determined at each station) and then calibrated according to the manufacturer’s specification.

Microglia are derived from hematopoietic stem cells in bone marro

Microglia are derived from hematopoietic stem cells in bone marrow. Some of these stem cells differentiate as monocytes and further differentiate as microglia in the brain (Ritter et al., 2006). Pb is sequestered in bone marrow. Studies are needed to examine whether Pb in bone marrow disrupts critical replenishment of the hematopoietic daughter cell pool, thus reducing the migration of adequate progenitor cell numbers to the brain. Finally, reduced numbers of IBA-1 labeled microglia may suggest that early chronic Pb exposure resulted in direct destruction of microglia. Astrocytes are

typically noted to be the brain’s “lead-sink.” The primary role of microglia however is to scavenge the Androgen Receptor antagonist brain for debris; further studies are needed to examine whether Selleckchem Androgen Receptor Antagonist microglia are destroyed by scavenged Pb particles. Very recent studies have illuminated the critical role of microglia in

brain development (Paolicelli et al., 2011). Additional studies are needed to examine whether pruning abnormalities are evident in mice with early chronic Pb exposure, and whether reduced numbers of functional microglia in lead exposed animals compromises the neuroimmune response system. Given the potential neurodegenerative effects of disrupted neuroimmune function, we also examined DG volume. As compared with controls, DG volume in both exposure groups was significantly decreased, and exposure groups did not differ significantly. Because both exposure groups received chronic dosing, the lack of difference between low and higher exposure groups with regard to DG volume suggested that the chronicity of exposure may have had more neuropathological significance than the amount of Pb to which the mice were exposed. Studies are needed to compare DG volume differences in cases of chronic versus acute exposure, to test how chronicity of

exposure influences the effects of early chronic Pb exposure on brain structure volume. Reduced DG volume could suggest either developmental delay of structure volume, or tissue deterioration in Pb-exposed animals. The lack of difference between low and higher Pb exposure groups suggested that whatever qualitative differences may exist between early chronic Pb exposure levels, Nintedanib (BIBF 1120) delay and/or deteriorative effects on development of dentate gyrus volume are not distinguishable in animals with low and higher exposures. We also examined the association between microglia number and DG volume, and regression analysis suggested that microglia number accounted for only a small amount of variation in DG volume, thus the volumetric differences are likely attributable to other sources, for example, disrupted integrity and/or numbers of other types of glia and/or neurons. Astrocytes are functionally linked to microglia (Section 1) and are far more abundant than microglia.

This is due, among other things, to the presence of

short

This is due, among other things, to the presence of

short-wave radiation known as Potentially Destructive Radiation (PDR), i.e. radiation in the spectral interval λ < 480 nm, especially that radiation readily absorbed by chlorophyll a in the Soret band. This problem is discussed in detail in Woźniak & Dera (2007). Chlorophyll molecules excited in this way have a good chance of shifting from the singlet state to the long-lived triplet state, which enhances the probability of their coming into contact with molecules of oxygen O2 and being photo-oxidized. To protect itself from such an eventuality, a plant synthesizes photoprotecting carotenoids, whose role it is to capture this excitation energy of chlorophyll molecules and then to dissipate it in a radiationless check details manner, which increases the quantum yield of heat production ΦH. The principal compound among the photoprotecting carotenoids is zeaxanthin, which is formed from violaxanthin in the so-called xanthophyll cycle ( Ruban & Horton 1999). The xanthophyll cycle consists of a whole set of processes, yet to be fully understood, in which mutual conversions of membrane xanthophylls take place in the thylakoids, especially the conversion of violaxanthin MAPK Inhibitor Library to zeaxanthin. The current state of knowledge of this problem is analysed in detail in the papers by Morosinotto et al. (2003), Latowski

et al. (2004), Standfuss et al. (2005) and Grzyb et al. (2006). The graphs shown mafosfamide in Figure 2 may also suggest that this quantum yield is dependent

not only on natural irradiance but also on other environmental parameters. These are: • a decrease in yield ΦH with increasing basin trophicity Ca(0), visible on all the plots in Figure 2 in the intervals of medium and low P AR irradiances; It should be noted, however, that the variability in the quantum yield of heat production ΦH ssociated with the basin trophicity Ca(0) at medium and low irradiances is small. These quantum yields most frequently lie within the limits from 0.7 ≤ ΦH ≤ 0.9, and hence in a narrow range of values with a half-width of roughly 20%. This also applies to the second feature of the variability in ΦH, that is, its model dependence on temperature. We anticipate, therefore, that these features may be encumbered by errors due to the inaccuracy of the model derived and presented in this paper. It was not developed on the basis of a statistical analysis of direct empirical measurements but indirectly, using two other model descriptions – those of the quantum yield of photosynthesis in the sea and the quantum yield of chlorophyll a fluorescence. These discrepancies, as already mentioned, may relate especially to the modelled changes in the yield ΦH caused by changes in trophicity and water temperature. Nevertheless, as shown above, the model description of the dependences of ΦH is correct and physically justified.

Yamazaki et al 12 quantificaram

a expressão de interleuci

Yamazaki et al.12 quantificaram

a expressão de interleucina (IL) 5 e 13 em adultos com EEo. Aeroalergénios e alergénios alimentares, incluindo ácaros do pó doméstico, pólenes como a artemísia e fungos como o Aspergillus, leite e soja, induziam nestes doentes uma produção de IL-5 significativamente superior à dos controlos atópicos, sugerindo que ambos os alergénios, inalatórios e alimentares, podem ter um papel importante na patogénese da EEo em adultos. A eficácia clínica Proteasome inhibitor e histológica das dietas de evicção de determinados alimentos13 e das dietas elementares14 fundamenta o papel da alergia nesta patologia, existindo até à data mais evidência na criança do que no adulto. As variações sazonais paralelas da inflamação eosinofílica esofágica e brônquica apoiam igualmente o papel dos aeroalergénios na patogénese desta doença15. Paralelamente, tem sido reportada a existência de predisposição genética. Cerca de 10% dos pais de doentes com EEo têm história de estenoses esofágicas e 8% confirmação histológica de EEo6. Polimorfismos no gene humano CCL26 (eotaxina-3) foram associados a um aumento da suscetibilidade para EEo16. O papel do esófago no processo de sensibilização ainda não está bem estabelecido. Não se sabe se

esta ocorre primariamente no esófago ou se surge infiltração eosinofílica após sensibilização noutro local do trato digestivo Dynein ou no trato respiratório17. O número de linfócitos T, células dendríticas e mastócitos está aumentado na camada epitelial do esófago Thiazovivin solubility dmso destes doentes, bem como as citocinas de perfil Th2 (IL-4, IL-5 e IL-13) e a eotaxina 318 and 19. O mecanismo

de ativação dos basófilos, com consequente libertação de histamina e outros mediadores e migração de eosinófilos, não está claro mas não parece ser exclusivamente mediado pela IgE20. Os eosinófilos e os diferentes mediadores inflamatórios que estes libertam desenvolvem e perpetuam o processo inflamatório local, levando a alterações macroscópicas e histológicas, bem como a alterações estruturais e funcionais17. As manifestações clínicas variam de acordo com a idade. Na idade pediátrica, a recusa alimentar, a dor abdominal, as náuseas e os vómitos são sintomas frequentes; por vezes, também surge má progressão ponderal. No adulto, os sintomas predominantes são a disfagia, a impacção alimentar e a pirose5. Os aspetos endoscópicos que surgem mais frequentemente nestes doentes, apesar de não serem patognomónicos, são edema e friabilidade da mucosa do esófago, estrias longitudinais, ponteados ou exsudados esbranquiçados, anéis circulares fixos ou transitórios que podem dar o aspeto de «traquealização» do esófago e estreitamento do lúmen. No entanto, alguns estudos têm reportado uma aparência normal da mucosa em 17 a 30% dos doentes.