Short-term perinatal oxygen exposure may impair lung development in adult mice

BACKGROUND: Hyperoxia at resuscitation increases oxidative stress, and even brief exposure to high oxygen concentrations during stabilization may trigger organ injury with adverse long-term outcomes in premature infants. We studied the long-term effects of short-term perinatal oxygen exposure on cell cycle gene expression and lung growth in adult mice. METHODS: We randomized mice litters at birth to 21,40, or 100%O2 for 30 min and recovered in room air for 4 or 12 weeks. Cell cycle gene expression, protein analysis, and lung morphometry were assessed at 4 and 12 weeks. RESULTS: The principal component analysis demonstrated a high degree of correlation for cell cycle gene expression among the three oxygen groups. Lung elastin was significantly lower in the 100%O2 groups at 4 weeks. On lung morphometry, radial alveolar count, alveolar number, and septal count were similar. However, the mean linear intercept (MLI) and septal length significantly correlated among the oxygen groups. The MLI was markedly higher in the 100%O2 groups at 4 and 12 weeks of age, and the septal length was significantly lower in the 100%O2 groups at 12 weeks. CONCLUSION: Short-term exposure to high oxygen concentrations lead to subtle changes in lung development that may affect alveolarization. The changes are related explicitly to secondary crest formation that may result in alteration in lung elastin. Resuscitation with high oxygen concentrations may have a significant impact on lung development and long-term outcomes such as BPD in premature infants.

Elastin increases biofilm and extracellular matrix production of Aspergillus fumigatus

Abstract Aspergillus fumigatus is an opportunistic saprobe fungus that accounts for 90% of cases of pulmonary aspergillosis in immunosuppressed patients and is known for its angiotropism. When it reaches the respiratory tract, A. fumigatus interacts with structural components and blood vessels of the lungs, such as elastin. To understand the effect of this structural component, we examined the effect of elastin on the production and development of the biofilm of A. fumigatus. In RPMI containing 10 mg/mL of elastin, a significant increase (absorbance p < 0.0001; dry weight p < 0.0001) in the production of biofilm was observed in comparison to when RPMI was used alone, reaching a maximum growth of 18.8 mg (dry weight) of biofilm in 72 h. In addition, elastin stimulates the production (p = 0.0042) of extracellular matrix (ECM) and decreases (p = 0.005) the hydrophobicity during the development of the biofilm. These results suggest that elastin plays an important role in the growth of A. fumigatus and that it participates in the formation of thick biofilm.

Histochemical and immunohistochemical differences between solitary oral fibroma and fibrous papule of the face

Abstract: Background: The morphological similarities between fibrous papules of the face and multiple sporadic oral fibromas were mentioned long ago and a relationship between them has been reported in the literature. Objective: The aim of this study was to evaluate the participation of mast cells, elastin and collagen in a series of oral fibromas and fibrous papules of the face in order to better understand the possible role of these factors in fibrosis and the formation of these lesions. Methods: Thirty cases of oral fibroma involving the buccal mucosa and 30 cases of fibrous papules of the face were selected. Tissue samples were submitted to picrosirius red staining and immunohistochemistry using anti-elastin and anti-tryptase antibodies. Results: The percentage of tryptase-positive mast cells and expression of elastin were higher in cases of fibrous papules of the face (p < 0.05). In contrast, a higher intensity of collagen deposition was observed in oral fibromas. The results showed mast cell accumulation and higher elastin synthesis in fibrous papules of the face, and mast cell accumulation with higher collagen fiber synthesis in oral fibromas. Conclusion: These findings support the hypothesis that mast cells influence the development and growth of these lesions through different mechanisms.

Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Objectives To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP). Materials and Methods This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13). Results According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both). Conclusions Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause. .

Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation

OBJECTIVES: Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction. MATERIALS AND METHODS: Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction. RESULTS: Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN) was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction. CONCLUSION: Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adiposederived stem cells was most prominent after one week of chondrogenic induction.

Estudo estrutural do pênis de fetos humanos normais e anencéfalos no segundo trimestre de gestação / Structural study of the penis of normal and anencephalic human fetuses in the second trimester of pregnancy

A anecencefalia é o Defeito do Tubo Neural (DTN) mais severo em fetos humanos. Há uma demanda crescente para reposição tissular em doenças crônicas e cirurgias reconstrutoras. Tecidos fetais têm sido utilizados como substitutos para órgãos sólidos. Comparar a estrutura e morfologia do corpo cavernoso e corpo esponjoso de pênis de fetos humanos anencéfalos e de controle a fim de propor um novo modelo para estudos biológicos e transplantes teciduais. Foram estudados 11 pênis de fetos de controle de 14 a 23 Semanas Pós Concepção (SPC), e cinco pênis de fetos anencéfalos de 18 a 22 SPC. Os órgãos foram removidos e processados pelas técnicas histo e imunohistoquímicas rotineiras. A análise do tecido conjuntivo, células musculares lisas e fibras elásticas foram realizadas em lâminas dos espécimes. Os dados foram expressos em Densidade de àrea (Da) utilizando-se um software de processamento digital. As médias foram comparadas utilizando-se o Teste - T não pareado e quando aplicável, a regressão linear simples foi utilizada. Foi considerada significância estatística se p<0,05. O septo intercavernoso encontrava-se presente em todas as amostras. Não foram observadas diferenças da Da do tecido colágeno e musculatura lisa dos pênis de fetos anencéfalos quando comparados aos normais. A regressão linear simples sugere que durante o desenvolvimento humano há um aumen2to gradual do tecido colágeno (R2=0,45) e uma diminuição da musculatura lisa (R =0,62) no corpo cavernoso de ambos os grupos. A elastina encontrava-se presente apenas em fetos a partir da 20ª SPC. Não houve diferença na estrutura da genitália entre fetos normais e enencéfalos. Apresença da elastina em fetos a partir da 20ª SPC é um dado objetivo da manutenção da capacidade de ereção nestes grupos. A histo e imunohistoquímica sugerem que o desenvolvimento do pênis destes fetos encontra-se inalterado. Futuros estudos deverão ser realizados com o objetivo de avaliar fetos anencéfalos como um potencial ...

Anencephaly is the most severe neural tube defect (NTD) in human fetuses. There is an increasing need for tissue replacement in chronic diseases and reconstructive surgeries. Fetal tissues have been used as a substitute for native organs. Compare the structure and morphology of the corpora cavernosa and spongiosum of penises from anencephalic and normal human fetuses to propose a new model for biological studies and tissue transplantation. We studied 11 penises from normal human fetuses, aged 14 to 23 weeks post-conception (WPC), and 5 penises from anencephalic fetuses, aged 18 to 22 WPC. The organs were removed and processed by routine histological and immunolabeling techniques. Analysis of connective tissue (Cot), smooth muscle (SMC) and elastic fibers (EF) were performed in sections. Data were expressed as area density (Ad) using digital processing and software. Means were statistically compared using the unpaired t test and linear regression was performed. Statistical significance was considered if p < 0.05. The Intracavernosal septum was present in all samples. We did not observe differences in the Ad of Cot and SMC in the penises of anencephalic fetuses when compared to normal ones. The simple linear regression suggested that during human development there is a gradual increase in Cot (R2= +0.45) and a decrease of SMC (R2=- 0.62) in the corpora cavernosa in both groups studied. Elastin was observed only in fetuses from 20th WPC. There was no difference in the structure of the corpora cavernosa and corpus spongiosum of anencephalic fetuses compared to normal ones. Elastin was documented from 20th WPC, which suggests the maintenance of erectile function. Histochemistry and immunolabeling suggested that penile shaft development is maintained and unaltered in anencephalic fetuses. Further studies should be performed to analyze anencephalic fetuses as a potential tissue donating group and a model for biological studies

Lung morphometry, collagen and elastin content: changes after hyperoxic exposure in preterm rabbits

INTRODUCTION: Elastic and collagen fiber deposition increases throughout normal lung development, and this fiber network significantly changes when development of the lung is disturbed. In preterm rats and lambs, prolonged hyperoxic exposure is associated with impaired alveolization and causes significant changes in the deposition and structure of elastic fibers. OBJECTIVES: To evaluate the effects of hyperoxic exposure on elastic and collagen fiber deposition in the lung interstitial matrix and in alveolarization in preterm rabbits. METHODS: After c-section, 28-day preterm New-Zealand-White rabbits were randomized into 2 study groups, according to the oxygen exposure, namely: Room air (oxygen = 21 percent) or Oxygen (oxygen > 95 percent). The animals were killed on day 11 and their lungs were analyzed for the alveolar size (Lm), the internal surface area (ISA), the alveoli number, and the density and distribution of collagen and elastic fibers. RESULTS: An increase in the Lm and a decrease in the alveoli number were observed among rabbits that were exposed to hyperoxia with no differences regarding the ISA. No difference in the density of elastic fibers was observed after oxygen exposure, however there were fewer collagen fibers and an evident disorganization of fiber deposition. DISCUSSION: This model reproduces anatomo-pathological injuries representing the arrest of normal alveolar development and lung architecture disorganization by just a prolonged exposition to oxygen. CONCLUSIONS: In the preterm rabbit, prolonged oxygen exposure impaired alveolization and also lowered the proportion of collagen fibers, with an evident fiber network disorganization.

Avaliação dos efeitos do oleo extraido dos grãos verdes de Coffea arabica L. e dos fitoesterois de Brassica campestris L na melhora da celulite e da gordura localizada / Study of the effects obtained with the oil extracted from the green seeds of Coffea arabica L. and phytoesterols of Brassica campestris L. in the cellulite improvement

Clinicamente, a celulite é definida como uma alteração na topografia da pele que ocorre principalmente em mulheres, na região pélvica, abdômen e membros inferiores, caracterizando-se pelo aspecto de "casca de laranja". Etiologicamente, celulite é definida como uma desordem metabólica localizada do tecido subcutâneo que provoca uma alteração na forma corporal, onde muitas estruturas são alteradas na derme, na micro circulação e, também, no tecido adiposo. Este fenômeno, por sua vez, está associado com modificações morfológicas, histoquímicas e bioquímicas na pele e resultam nas alterações que levam ao desconforto estético e à aparência clínica da celulite. Partes destas alterações decorrem do acúmulo de lipídeos no interior de adipócitos, células chave no equilíbrio lipólise-lipogênese, o qual é visto hoje como uma unidade glandular funcional capaz de promover uma relação direta com o sistema nervoso central. Pesquisas atuais indicam que a busca por substâncias capazes de promover a homeostase dermo-hipodérmica através de uma ação lipolítica direta, aliada ao estímulo da produção de fatores de crescimento, especialmente TGF-? e GM-CSF, bem como de proteínas da matriz extracelular, como colágeno, elastina e GAGs, além de substâncias reguladoras do metabolismo adipocitário. Tendo em vista a complexidade clínica e estética da celulite, bem como as alterações bioquímicas dérmicas e hipodérmicas, buscamos neste trabalho avaliar os efeitos da associação entre o extrato oleoso dos grãos verdes de café (Coffea arabica L.) (OC) e os fitoesteróis de canola (Brassica campestris L.) (F), cuja combinação resulta no produto Slimbuster® L (SBL). Para isto, avaliamos neste estudo os efeitos in vitro (fibroblastos e adipócitos humanos), ex-vivo (fragmentos de pele humana) e clínicos (voluntários humanos) de SBL...

Cellulite is an alteration of the topography of the skin that occurs mainly in women on the pelvic region, lower limbs and abdomen. It is characterized by a padded or 'orange peel' appearance. In according with its etiology, cellulite is defined as a metabolic located disorder of the subcutaneous tissue that provokes an alteration in the physical form, where many structures are alterated in the dermis, in the microcirculation and within the adipocytes. This phenomenon is associated to morphological, histochemical and biochemical modifications in the skin, culminating in the alterations that lead to the aesthetic discomfort and to the clinical appearance of the cellulitis. These alterations are consequence, in parts, from the lipid accumulation into the adypocites, crucial cells in the lypolisis-lipogenesis balance, and it is considerate as a glandular functional unity able to promote a fine-tune interaction with the central nervous system. Recent studies indicate the search for active substances with the ability of promote the dermo-hypodermic homeostasis through lipolytic action, allied to the stimulus of the production of growth factors, mainly TGF-? and GM-CSF, proteins of extracellular matrix, such as collagen, elastin and glycosaminoglycans, as well as substances ables to regulate the adipocyte metabolism. According to the clinical and aesthetic complexity of the cellulitis, as well as the biochemical alterations in the dermis and hypodermis, in this work we evatuate the effects...

The Increased Expression of Matrix Metalloproteinases Associated with Elastin Degradation and Fibrosis of the Ligamentum Flavum in Patients with Lumbar Spinal Stenosis

BACKGROUND: One of the characteristics of spinal stenosis is elastin degradation and fibrosis of the extracellular matrix of the ligamentum flavum. However, there have been no investigations to determine which biochemical factors cause these histologic changes. So we performed the current study to investigate the hypothesis that matrix metalloproteinases (MMPs), which possess the ability to cause extracellular matrix remodeling, may play a role as a mediator for this malady in the ligamentum flavum. METHODS: The ligamentum flavum specimens were surgically obtained from thirty patients with spinal stenosis, as well as from 30 control patients with a disc herniation. The extents of ligamentum flavum elastin degradation and fibrosis were graded (grade 0-4) with performing hematoxylin-eosin staining and Masson's trichrome staining, respectively. The localization of MMP-2 (gelatinase), MMP-3 (stromelysin) and MMP-13 (collagenase) within the ligamentum flavum tissue was determined by immunohistochemistry. The expressions of the active forms of MMP-2, MMP-3 and MMP-13 were determined by western blot analysis, and the blots were quantified using an imaging densitometer. The histologic and biochemical results were compared between the two conditions. RESULTS: Elastin degradation and fibrosis of the ligamentum flavum were significantly more severe in the spinal stenosis samples than that in the disc herniation samples (3.14 +/- 0.50 vs. 0.55 +/- 0.60, p < 0.001; 3.10 +/- 0.57 vs. 0.76 +/- 0.52, p < 0.001, respectively). The expressions of the active form of MMPs were identified in all the ligamentum flavums of the spinal stenosis and disc herniation patients. The expressions of active MMP-2 and MMP-13 were significantly higher in the spinal stenosis samples than that in the disc herniation samples (both p < 0.05). The expression of active MMP-3 was slightly higher in the spinal stenosis samples than that in the disc herniation samples, but the difference was not statistically significant (p = 0.131). MMP-2, -3, and -13 were positively stained on the ligamentum flavum fibroblasts. CONCLUSIONS: The current results suggest that the increased expression of active MMPs by the ligamentum flavum fibroblasts might be related to the elastin degradation and fibrosis of the ligamentum flavum in the patients who suffer with lumbar spinal stenosis.

Effects of Infrared Radiation on Skin Photo-Aging and Pigmentation

Infrared radiation is increasingly and uncritically used for cosmetic and wellness purposes, despite the poorly understood biologic effects of such treatments on humans. In the present study, we investigated the effects of infrared radiation on collagen and elastin production in dermal fibroblasts, as well as the clinical and histopathologic effects of infrared radiation on photo-aged facial skin lesions. In order to determine the effects of infrared radiation on collagen and elastin production, dermal fibroblasts were exposed to infrared radiation for varying lengths of time and collagen and elastin contents were subsequently determined. Additionally, 20 patients with mild to moderate facial wrinkles and hyperpigmented lesions received daily treatments of far infrared radiation (900 to 1000micronm) for six-months. During the treatment, patients and a medical observer conducted independent photographic and clinical evaluations every 4 weeks, and skin biopsies were obtained for histological analysis at baseline and one month post-treatment. We found that the content of collagen and elastin produced by the fibroblasts increased after infrared radiation, and that this increase was proportional to the duration of irradiation exposure. Following 6 months of treatment, all patients reported good (51-75%) improvements in skin texture and roughness. Additionally, patients noted fair (25-50%) improvement in color tone of the skin; however, improvements in hyperpigmented lesions were not observed. Objective medical evaluation of the patients indicated that roughness and laxity were fairly improved, but there was no significant improvement in hyperpigmented lesions. Histological examination failed to reveal any differences as well. These results suggest that infrared radiation may have beneficial effects on skin texture and wrinkles by increasing collagen and elastin contents from the stimulated fibroblasts. Therefore, skin treatment with infrared radiation may be an effective and safe non-ablative remodeling method, and may also be useful in the treatment of photo-aged skin.

The role of the collagenous and elastic system fibers in modulating bronchoconstriction

The distribution and conformational changes of the fibers of the collagenous and elastic systems in guinea pig airways after a contractile agonist challenge are described. We observed a distinct pattern of behavior within the mucosal fibers during bronchoconstriction. Part of the fibers of the two systems tend to follow the epithelial invaginations towards the airway lumen, while the remaining ones seem to be attached to the internal smooth muscle. These layers of fibers in the mucosa are interconnected to one another and to the adventitial network by slender fibers. We suggest that the configuration and behavior of these fibers during bronchoconstriction may contribute to airway reopening after the contractile stimulus has ceased. The possible role of this mechanism in the pathophysiology of human asthma is discussed.

Las fibras elásticas y el pulmón / The elastic fibers and the lung

La matriz extracelular (ME) del tejido conectivo pulmonar se diferencia en membranas basales y matriz intersticial. Esta última se constituye por un armazón de proteínas colagénicas fibrosas y de fibras elásticas amorfas, que están embebidas dentro de una sustancia basal viscoelástica compuesta por proteoglicanos y glicoproteínas. La ME le proporciona al pulmón sus propiedad mecánicas. Las colágenas proveen tensión, mientras que las fibras elásticas permiten el desarrollo de la expansión elástica, con la subsecuente recuperación característica de este órgano. Las fibras elásticas se constituyen por fibras amorfas de elastina polimérica combinada con ciertas glicoproteínas conocidas como microfibrillas, con proporciones variables según su estadio ontogénico. Este material amorfo constituye toda una malla que comprende un armazón continuo, por todo el pulmón, y en conexión estrecha con las fibras de colágena permite la actividad mecánica del pulmón. La elastina es una molécula altamente hidrofóbica, con una relación intron: exón de 15:1, sintetizada junto con un receptor que guía su polimerización en sitios determinados por las microfibrillas previamente depositadas

Production of serine chymotrypsin-like elastate by aspergillus fumigatus strains

Treinta y cuatro cepas de Aspergillus fumigatus aisladas del aire, crín de caballo, suelo agrícola y del hombre, fueron examinadas con el fin de evaluar la producción de elastasa. Las cepas de Aspergillus fumigatus fueron cultivadas en un medio sólido con elastina, apreciándose en ella su amplio solubilización por la acción del hongo. Los aislamientos fúngicos provenientes de muestras aisladas del hobre y de suelos agrícolas fueron detectados como los más altos productores de elastasa. Ocho de las 34 cepas fueron desarrollas en 4 diferentes medios líquidos en las cuales se investigó la actividad proteolítica total y específica. Los resultados de este experimento sugieren que la producción de elastasa es inducida por la presencia de elastina como sustrato y que la primera es una enzima semejante a la quimiotripsina. El perfil inhibitorio comprobó que la elastina de A.fumigatus, es una serina-proteinasa

Development of elastin layers in the aortic wall of human fetuses

The presence of elastin layers in the aortic walls of twelve human fetuses was confirmed with scanning electron microscope pictures after hot alkali treatment and histochemical examination. In addition, the number of elastin layers in aortic walls of 5 different segments were compared in fetuses of varying ages. Aldehyde fuchsin stained slides of elastin ascending aortas showed a range between 27 and 55 layers of elastin in fetuses of 8 weeks to 32 weeks. However, in the lower abdominal aortas, elastin layers decreased from 28 to only 3 layers for fetuses of the same age. Furthermore, as elastin layers decreased from ascending aorta to abdominal aorta with the progression of fetal life, similar changes in the elastin lamellae were observed. These results suggest that while aortas grow rapidly in length, the medial elastin thickens slowly, perhaps due to slow development of hydrodynamic forces and pressures. Also the adventitial elastin appears to lose out gradually along the length from ascending aorta to abdominal aorta.

Actividad proteolítica y elastásica de Pseudomonas aeruginosa / Study of the enzymatic activity of 20 strains of Pseudomonas aeruginosa

Se estudia la capacidad productora de proteasas extracelulares de cepas de Pseudomonas aeruginosa, usándose como sustrato gelatina, caseína y elastina. Se usan tres medios de cultivo de distinta complejidad y contenido proteico para medir dicha actividad: a) medio base mineral constituído por sales y extracto de levadura; b) medio dializante, formado por pequeños péptidos que atraviesan el saco de diálisis, provenientes de caldo-cerebro-corazón más glucosa 50 mM y c) medio complejo constituído por caldo-cerebro-corazón. Se selecciona éste último por ser el mejor productor de las enzimas. La purificación de las mismas se efectuó por precipitación con sulfato de amonio al 60% y filtración molecular por Sephadex G - 100. El número de enzimas que actuaron sobre caseína se determinó por zimograma, previa separación en geles de poliacrilamida, número que se corroboró por cromatografía en Sephadex. Las 20 cepas estudiadas se seleccionaron por licuar la gelatina. Todas actuaron sobre caseína y el 80% degradó la elastina. El 25% de las cepas mostraron la presencia por zimograma, de dos formas moleculares; el resto una sola. El número de éstas fue independiente del medio de cultivo empleado, ya que dicho porcentaje se obtuvo trabajando con un mismo medio. Tampoco se encontró dependencia con el origen del material del cual se aisló la cepa. Las cepas recién aisladas fueron buenas productoras de enzimas proteolíticas, no así las mantenidas en el laboratorio. La actividad enzimática se fue perdiendo con el envejecimiento de las cepas, desapareciendo también las formas moleculares menos activas reveladas por el zimograma. La tinción de los geles de poliacrilamida reveló la presencia de polipéptidos, no así de lipo-y glicoproteínas