Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque

The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques.Ovariectomized rhesus macaques (n 66) were treated with estradiol (E-2), E-2 plus progesterone, E-2 followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid- and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR).MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E-2 alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E-2 stimulated MMP-26 expression in the early and mid-secretory phases (P 0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P 0.01) despite continued E-2 plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR.Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid- and late secretory phases may play a role in the receptive window for embryo implantation.

Functional and Structural Adaptations in the Pancreatic alpha-Cell and Changes in Glucagon Signaling During Protein Malnutrition

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Doença arterial coronariana: Um novo paradigma na AIDS

The HIV-infected individuals have been identified as a peculiar group whose propensity to the development of abnormalities in lipids metabolism supports the hypothesis that AIDS itself can be considered as an independent risk factor for the occlusive diseases development. The AIDS progression, as well as the therapy against HIV has been capable to show an array of metabolic disturbances that HIV-infected patients are prone to. These metabolic alterations affect the fate of plasmatic lipids and homocysteine as a result of three factor mainly: (i) the viral infection per se which triggers the development of hypertriglyceridemia and hipocholesterolemia; (ii) multiple vitamins and micronutrients deficiencies, that favors an onset of hyperhomocysteinemia; (iii) the state-of-the-art therapy for HIV infection, which is accompanied to idiosyncratic effects encompassing the lipid metabolism. In this context, a variety of risk factors to atherosclerosis can be identified in the HIV-infected individual. Of note, it must be considered that once life expectancy of these patients has been expanded due to the effective therapy, on the other hand they can accelerate atherosclerotic disease or its pathological appearance in the same extent.

Effects of nitric oxide and arginine vasopressin on sodium intake induced by central angiotensin II. Part 2

We study the effects of angiotensin receptors antagonists, arginine vasopressin receptor antagonist, L-arginine and L-NAME, injected into supraoptic nucleus of the hypothalamus (SON) on sodium intake induced by the injection of angiotensin II (ANGII). Holtzman rats weighing 200-250 g with canulae implanted into the SON were used. The drugs were injected in 0.5 μL over 30-60 sec. Sodium intake after injection of saline SAL+SAL 0.15 M NaCl was 0.10±00.1 mL 2 h -1; SAL+ANGII injected into SON increased sodium intake. Losartan injected prior to ANGII into SON decreased sodium intake induced by ANGII. PD123319 injected prior to ANGII produced no changes in sodium intake induced by ANGII. AVPA receptor V 1 antagonist injected prior to ANGII reduced sodium intake with a less intensity than losartan. L-arginine injected prior to ANGII decreases sodium intake at a same intensity than losartan. L-NAME injected prior to ANGII potentiated sodium intake induced by ANGII. Losartan injected simultaneously with L-arginine prior to ANGII blocked the natriorexigenic effect of ANGII. These results confirm the importance of SON in the control of sodium intake. Also suggest that both AT 1 and arginine vasopressin V 1 receptors interact with nitrergic pathways within the SON influencing the sodium metabolism by changing sodium appetite induced by ANGII. © 2007 Asian Network for Scientific Information.

Variation in the CXCR1 gene (IL8RA) is not associated with susceptibility to chronic periodontitis

Background: The chemokine receptor 1 CXCR-1 (or IL8R-alpha) is a specific receptor for the interleukin 8 (IL-8), which is chemoattractant for neutrophils and has an important role in the inflammatory response. The polymorphism rs2234671 at position Ex2+860G > C of the CXCR1 gene causes a conservative amino acid substitution (S276T). This single nucleotide polymorphism (SNP) seemed to be functional as it was associated with decreased lung cancer risk. Previous studies of our group found association of haplotypes in the IL8 and in the CXCR2 genes with the multifactorial disease chronic periodontitis. In this study we investigated the polymorphism rs2234671 in 395 Brazilian subjects with and without chronic periodontitis. Findings. Similar distribution of the allelic and genotypic frequencies were observed between the groups (p > 0.05). Conclusions: The polymorphism rs2234671 in the CXCR1 gene was not associated with the susceptibility to chronic periodontitis in the studied Brazilian population. © 2011 Scarel-Caminaga et al; licensee BioMed Central Ltd.

An Integrative Genomic and Transcriptomic Analysis Reveals Potential Targets Associated with Cell Proliferation in Uterine Leiomyomas

Background: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs. Methodology: We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data. Principal Findings: The integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively) and IGFBP5 (P = 0.0002 and P = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium. Conclusions: The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs. © 2013 Cirilo et al.

Análise dos parâmetros clínicos periodontais e expressão genética de interferons alfa, gama e genes relacionados em indivíduos portadores de Síndrome de Down com doença periodontal

Pós-graduação em Ciências Odontológicas - FOAR

Avaliação do padrão de metilação de regiões promotoras dos genes ESR1, ESR2 e PGR na endometriose profunda intestinal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis

Endometriosis is a continuous and progressive disease with a poorly understood aetiology, pathophysiology and natural history. This study evaluated the histological differences between eutopic and ectopic endometria (abdominal wall endometriosis) and the expression of mast cell proteases (tryptase and chymase), annexin A1 (ANXA1) and formyl peptide receptor 1 (FPR1). Ectopic endometrium from 18 women with abdominal wall endometriosis and eutopic endometrium from 10 women without endometriosis were obtained. The endometrial samples were analysed by histopathology, immunohistochemistry and ultrastructural immunogold labeling to determine mast cell heterogeneity (tryptase and chymase positive cells) and the expression levels of ANXA1 and FPR1. Histopathological analysis of the endometriotic lesions showed a glandular pattern of mixed differentiation and an undifferentiated morphology with a significant influx of inflammatory cells and a change in mast cell heterogeneity, as evidenced by a significant increase in the number of chymase-positive cells and endogenous chymase expression. The undifferentiated glandular pattern of endometriotic lesions was positively associated with a marked increase and co-localization of ANXA1 and FPR1 in the epithelial cells. In conclusion, the co-upregulated expression of mast cell chymase and ANXA1–FPR1 system in ectopic endometrium suggests their involvement in the development of endometriotic lesions.

Efeitos do hormônio do crescimento sobre vias de sinalização intracelular na miopatia associada à insuficiência cardíaca de ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Orexin in the toad Rhinella schneideri: The location of orexinergic neurons and the role of orexin in ventilatory responses to hypercarbia and hypoxia

Recent reports have suggested that orexins, also known as hypocretins, play an important role in the modulation of respiratory control in mammals, but there are no data available describing the role of the orexinergic system in the peripheral and central chemoreception of non-mammalian vertebrates. Therefore, the present study was designed to examine the localization of orexin-immunoreactive neurons in the brain of toads (Rhinella schneideri) and to investigate the contribution of orexin receptor-1 (OX1R) to the hypoxic and hypercarbic ventilatory responses of these animals during light and dark phases. Our results demonstrated that the orexinergic neurons of R. schneideri are located in the suprachiasmatic nucleus of the diencephalon. Additionally, the intracerebroventricular injection of SB-334867 (OX1R selective antagonist) attenuated the ventilatory response to hypercarbia during the dark phase by acting on tidal volume and breathing frequency, while during the light phase, SB-334867 attenuated the ventilatory response to hypoxia by acting on tidal volume only. We conclude that in the toad R. schneideri, orexinergic neurons are located in the suprachiasmatic nucleus and that OX1R contributes to hypercarbic and hypoxic chemoreflexes.

A iteratividade: do melodrama à narrativa audiovisual sob demanda

The repetition should be understood as the property of mass cultural products, originated from the need to minimize the dispersion of the audience in their enjoyment. Based on this assumption, this paper measures the rate of iteration manifested in the scripts of the following serial fictions: Duas Caras, A Grande Família and House of Cards. Established itself as a method of scene analysis proposed by McKee (2008), questioned whether the lack of classical education of the public and rescued the forms assumed by repeating the melodrama, romance-serial and dramaturgy: asides, monologues, confidences and planar scenes. The proposal was applied in two scripts for each of the aforementioned productions. Considering the data collected, it appears that there was reduction in repeat products offered on demand thanks to the possibility of handling the flow and the attention given receptor.