RESUMO
In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.
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Previous studies demonstrated that many environmental chemicals can cross the human placental barrier. However, the risk regarding gestational exposure of emerging endocrine-disrupting chemicals (EDCs) is unclear. In this study, the occurrence of 24 EDCs, such as bisphenol A analogs, parabens, triclocarban, and triclosan, was investigated in serum and urine samples from Chinese pregnant women. Some metabolites were determined in matched serum-urine pairs (n = 75) to perform a comprehensive assessment of exposure. The placental transfer efficiency (PTE) of the detected chemicals was determined in matched maternal-cord serum pairs (n = 110). The mean PTEs of the chemicals showed a large variation from 43.1% to 171.0%. The potential effects of physicochemical properties, molecular structures, and biological factors on PTE were investigated using multiple linear regression models and molecular docking. We found that the PTE of methyl paraben, ethyl paraben, and propyl paraben was associated with their increasing alkyl chain lengths. Furthermore, a comprehensive exposure assessment of EDCs showed that 62.7% of pregnant women had a health index > 1, which indicted potential health risks during pregnancy. However, toxicity and the underlying mechanisms of these EDCs remain to be further studied.
Assuntos
Disruptores Endócrinos , Gestantes , Humanos , Feminino , Gravidez , Parabenos/toxicidade , Disruptores Endócrinos/toxicidade , Simulação de Acoplamento Molecular , Placenta/metabolismoRESUMO
Many per- and polyfluoralkyl substances (PFASs) may disrupt maternal thyroid hormone homeostasis in pregnancy. Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus. In this study, we measured the concentrations of 13 PFASs, including five novel short-chain PFASs, in serum from 123 pregnant women in Beijing, China. Linear regression models were used to investigate the association between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and PFASs concentrations under consideration of the impacts of pregnancy-induced physiological factors. We found that perfluorobutanoic acid (PFBA) (ß=0.189, 95%CI=-0.039, 0.417, p=0.10) and perfluorodecanoic acid (PFDA) (ß=-0.554, 95%CI=-1.16, 0.049, p=0.071) were suggestive of significant association with TSH in thyroid peroxidase antibody (TPOAb) negative women. No association was observed between all PFASs and FT4 levels after controlling for these confounding factors, such as BMI, gestational weight gain and maternal age. These findings suggest that it should pay more attention to the association between thyroid hormone levels and short-chain PFASs concentrations. Future studies could consider a greater sample and the inclusion of other clinical indicators of thyroid function, such as free T3 and total T3.
Assuntos
Fluorocarbonos , Feminino , Humanos , Iodeto Peroxidase , Gravidez , Gestantes , Hormônios Tireóideos , Tireotropina , TiroxinaRESUMO
BACKGROUND: Perfluoroalkyl substances (PFASs) exist extensively and several of these have been verified to be toxic. Prenatal exposure to PFASs has attracted much attention. Metabolome-wide association analyses can be used to explore the toxicity mechanisms of PFASs by identifying associated biomarkers. OBJECTIVES: To evaluate associations between the metabolites in maternal and cord serum and internal exposure to several common PFASs. METHODS: Paired maternal and cord serum samples were collected from 84 pregnant women who gave birth between 2015 and 2016. Seven legacy and two novel PFASs were measured. A nontarget metabolomic method and an iterative metabolite annotation based on metabolic pathways were applied to characterize the metabolic profiles. Linear regression adjusted with the false discovery rate and covariates was used to indicate the associations. RESULTS: A total of 279 features in maternal serum and 338 features in cord serum were identified as metabolites associated with PFAS exposure. Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS) were two PFASs associated with more metabolites, while the two novel chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) showed less relevance to the metabolome. With pathway enrichment analysis, we found that three fatty acid metabolisms and retinol metabolism were correlated with PFAS exposure in maternal blood, and that sterol metabolism showed the correlation in both maternal serum and cord serum. CONCLUSIONS: We identified metabolites and pathways in pregnant women and fetuses associated with the exposure to several PFAS, indicating a promising application for metabolome-wide association studies. Additional research is needed to confirm causation.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Feminino , Feto , Fluorocarbonos/toxicidade , Homeostase , Humanos , Metaboloma , Gravidez , GestantesRESUMO
Spontaneous abortion is a common, detrimental outcome of pregnancy, and can be induced by a variety of factors, including pathophysiological conditions and socioeconomic circumstances. Despite numerous studies examining the aetiology of spontaneous abortion, there is limited understanding of the disordered iron transportation between mother and fetus through the placenta. Recently, erythroferrone (ERFE) was recognized as a novel negative regulator of hepcidin that can elevate nutritional iron absorption and macrophagic iron egress for enhanced erythropoiesis. However, its diagnostic significance in different disease conditions associated with iron remains poorly understood. In the current study, we discovered disordered maternal iron homeostasis in women who had spontaneous abortions during early pregnancy, as characterized by increased serum iron and hepcidin levels, and conversely, reduced serum ERFE levels, compared to healthy control individuals and women with normal pregnancy. Comprehensive statistical analyses revealed the correlation between different variables and pregnancy status, signifying the pronounced diagnostic value of an increased ratio of serum hepcidin and ERFE (HE ratio) in recognizing adverse pregnancy status. In contrast to previous non-selective discrete surrogates, such as iron, hepcidin and ferritin, the HE ratio may otherwise stand for a novel and more representative hallmark for early spontaneous abortion.
Assuntos
Aborto Espontâneo/sangue , Hepcidinas/sangue , Hormônios Peptídicos/sangue , Aborto Espontâneo/metabolismo , Adulto , Feminino , Humanos , Ferro/metabolismo , Gravidez , PrognósticoRESUMO
Spontaneous abortion is a considerable threat to the physiology and mental health of the mother. The etiology of spontaneous abortion is multifactorial with complicated mechanisms, of which overexposure to non-essential metals (especially heavy metals) has been proposed to be associated with adverse birth outcomes. However, significant knowledge gaps remain to be filled in, such as the deleterious profile of non-essential metals and their interplay with essential metals in abnormal pregnancy. Under this setting, we aimed to address these challenges by conducting a cross-sectional study on 56 patients with spontaneous abortion in the 1st trimester, by comparing to 55 healthy pregnant women in 1st the trimester and 41 non-pregnant healthy women. Overexposure to a few non-essential metals, such as arsenic (As), antimony (Sb) and bismuth (Bi), was found in patients with spontaneous abortion, and likewise, some essential elements, such as magnesium (Mg), copper (Cu), vanadium (V), strontium (Sr) and tin (Sn), were also found to be elevated under spontaneous abortion. Further evidence of abnormal pregnancy was induced by a reduced level of internal hormones necessary for normal gestation, such as estradiol (E2) and progesterone (PRGE) in women with spontaneous abortion. Lactate dehydrogenase (LDH) and thyroid-stimulating hormone (TSH) levels were slightly increased in patients with spontaneous abortion. Comprehensive correlation analyses were carried out to identify the crucial factors that result in abortion. Our data stratified the important variables in decreasing order: PRGE, As, Mg, Sb, Sr, Sn, Bi and pregnant times in the progress of spontaneous abortion. Moreover, labyrinthine associations were uncovered between PRGE, non-essential metals and essential elements in causing spontaneous abortion. Therefore, our combined data unveiled the likely synergistic implications of elevated non-essential metals and the disordered metabolism of essential metals in abnormal pregnancy.
Assuntos
Aborto Espontâneo , Arsênio , Metais Pesados , Complicações na Gravidez , Aborto Espontâneo/epidemiologia , Estudos Transversais , Feminino , Humanos , Metais Pesados/toxicidade , GravidezRESUMO
Despite mass production and widespread use of parabens, triclosan (TCS), and triclocarban (TCC) in a range of personal care products, little is known about their concentrations and distribution in pregnant woman serum in China. In this study, 5 parabens (methyl- (MeP), ethyl- (EtP), butyl- (BuP), heptyl- (HeP) and benzyl-parabens (BzP)) and 4 their metabolites (methyl protocatechuate (OH-MeP), ethyl protocatechuate (OH-EtP), 3,4-dihydroxybenzoic acid (3,4-DHB) and 4-hydroxybenzoic acid (4-HB)), TCS, and TCC were measured, by using solid-phase extraction (SPE) and ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) techniques, in pregnant woman serum samples collected from 13 provinces in China. Total concentrations of parabens (∑PBs), their metabolites (∑MBs), and TCC and TCS (∑AAs) in serum ranged from 0.221-18.6 (geometric mean (GM): 2.47), 47.4-598 (212), and 0.101-5.84 (1.01) ng/mL, respectively. MeP, EtP, 4-HB and TCS were the dominant compounds, and their GM concentrations were 1.86, 0.239, 211 and 1.00 ng/mL, respectively. Geographical distribution of target chemicals in serum was determined. Concentrations of MeP (5.49 ng/mL) and EtP (0.895 ng/mL) in sera from the Northeast China were higher than those from other regions (MeP: 0.987-3.54, EtP: 0.07-0.254 ng/mL; p < 0.05). The highest 4-HB concentrations were found in sera from the Southwest China (GM: 286 ng/mL), whereas the TCS concentrations in sera from the North China (1.18 ng/mL) were higher than those found for other regions (p < 0.05). The estimated daily intakes (EDIs; range: 49.5-126 µg/kg body weight (bw)/day) showed that the Chinese women were in a low health risk from exposure to such chemicals. This is the first study to report concentration profiles of parabens, TCS and TCC in pregnant woman serum in China.
Assuntos
Carbanilidas/análise , Parabenos/análise , Triclosan/análise , China , Cromatografia Líquida , Feminino , Humanos , Gravidez , Espectrometria de Massas em TandemRESUMO
There is increasing concern regarding human exposure to bisphenol analogues (BPs) due to their widespread use and potentially adverse effects. Nevertheless, information on the occurrence of BPs in pregnant women is limited. In this study, BPs were detected in 181 serum samples from pregnant Chinese women. Ten BPs, including bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol P (BPP), bisphenol Z (BPZ), bisphenol AP (BPAP), tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), and tetrachlorobisphenol A (TCBPA), were positively identified and quantified in serum samples with total BP concentrations (sum of bisphenols: ∑BPs) of 0-144 ng/mL. Concentrations of the two frequently detected compounds, TBBPS and BPS, were 0.593 and 0.113 ng/mL, respectively. The results were also compared with the geographic distributions of the BPs. To our knowledge, this is the first time that TBBPS and TCBPA have been detected in serum samples of pregnant women. These findings suggest that additional studies are urgently needed to identify the risk of maternal and fetal exposure to these compounds.
Assuntos
Compostos Benzidrílicos/sangue , China , Feminino , Humanos , GravidezRESUMO
Fluorene-9-bisphenol (BHPF), a new derivative of bisphenol A (BPA), has been introduced for treatment with estrogen-related tumors, such as endometrial cancer. This study investigated the potential mechanism underlying the action of BHPF against endometrial cancer in vitro. We used the cell counting kit-8 (CCK8) method on Ishikawa cells to screen sub-lethal doses of BHPF and established the optimal concentration at which BHPF influenced the proliferation of Ishikawa cells. Effect of BHPF on cell migration and invasion was investigated by cell scratch assay and transwell assay, respectively. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot analysis. BHPF was found to inhibit the proliferation of Ishikawa cells, whose migration and invasion abilities were also reduced. Western blot indicated that BHPF can significantly inhibit the EMT process of Ishikawa cells by blocking transforming growth factor-ß (TGF-ß) signaling pathway. This is the first report of the effect of BHPF on the biological behavior of endometrial cancer cells and its inhibition of endometrial cancer progression by repressing both endometrial cell proliferation and epithelial-mesenchymal transition, hence suggesting it as a novel anti-cancer drug. Graphical abstract Schematic representation of the molecular basis underlying BHPF treatment. BHPF repressed the EMT process by regulating EMT-related genes, such as E-cadherin, N-cadherin, and vimentin as well as the TGF-ß signaling pathway-related genes, including p-Smad2/3 and slug, in a BHPF-dependent manner.
Assuntos
Antineoplásicos/farmacologia , Compostos Benzidrílicos/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fluorenos/farmacologia , Fenóis/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Vimentina/metabolismoRESUMO
Information on placental transfer and adverse outcomes of short-chain per- and polyfluoroalkyl substance (PFASs) is limited, and factors responsible for PFAS placental transfer are still unclear. In the present study, concentrations of 21 PFASs were analyzed in 132 paired maternal and cord serum samples collected from residents in Beijing, China, and the placental transfer efficiency (PTE) of each PFAS was calculated. PTEs of short-chain perfluoroalkyl acids (PFAAs), including PFBA (146%), PFBS (97%), PFPeA (118%), and PFHxA (110%), were first reported, and a complete U-shaped trend of PTEs from C4 to C13 of perfluoroalkyl carboxylic acids (PFCAs) was obtained. Positive association between maternal weight and PTE of perfluorooctanesulfonate (PFOS) ( p < 0.05) and negative association between maternal PFBA concentration and birth length ( p < 0.01) were observed. Using in vitro experiments, we further determined equilibrium dissociation constants ( Kds) of human serum albumin (HSA)-PFAS complexes ( Kd-HP), serum proteins-PFAS complexes ( Kd-SP), and liver-fatty acid binding protein (L-FABP)-PFAS complexes ( Kd-LP) and found that they were all significantly correlated with PTEs of PFASs. The correlation coefficient was 0.92, 0.89, and 0.86, respectively ( p < 0.01 in all three tests), suggesting that Kds of protein (serum)-PFAS complexes can play an important role in trans-placental transfer of PFASs in human and Kd-HP plays a pivotal role.
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Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Pequim , Proteínas Sanguíneas , China , Feminino , Humanos , GravidezRESUMO
This study aimed to determine the effect of exposure to heavy metals in pregnant women in Beijing, China. We also evaluated the association of these heavy metals with birth weight and length of newborns. We measured the levels of 10 heavy metals, including lead (Pb), titanium (Ti), manganese (Mn), nickel (Ni), cadmium (Cd), chromium (Cr), antimony (Sb), stannum (Sn), vanadium (V), and arsenic (As), in 156 maternal and cord blood pairs. An inductively coupled plasma mass spectrometry method was used for measurement. Pb, As, Ti, Mn, and Sb showed high detection rates (>50%) in both maternal and cord blood. Fourteen (9%) mothers had blood Pb levels greater than the United States Center for Disease Control allowable threshold limit for children (50⯵g/L). In prenatal exposure to these heavy metals, there was no significant association between any heavy metal and birth weight/length. Moreover, we estimated the placental transfer efficiency of each heavy metal, and the median placental transfer efficiency ranged from 49.6% (Ni) to 194% (Mn) (except for Cd and Sn). The level and detection rate of Cd in maternal blood were much higher than that in cord blood, which suggested that Cd had difficulty in passing the placental barrier. Prospective research should focus on the source and risk of heavy metals in non-occupationally exposed pregnant women in Beijing.
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Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Exposição Materna , Metais Pesados/metabolismo , Adulto , Pequim , Criança , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Placenta/metabolismo , GravidezRESUMO
It is recognized that the stability and journey in the body of nanoparticles are important issues for drug formulations. In this study, we prepared folate-conjugated pullulan acetate nanoparticles (FPANs) and epirubicin loaded FPANs (FPA/EPI) using dialysis method. The storage stability of FPANs and FPA/EPI at 4 degrees C could be up to 3 months. Using folate receptor overexpressed Hela cells, dose dependent cellular uptake and receptor-mediated endocytosis of FPA/EPI were confirmed. From the in vivo pharmacokinetics test, compared to free EPI, half-life time (t½) of FPA/EPI was extended 1.57 times and the area under-the-curve (AUC) increased 3.95 times as well. In addition, biodistribution data showed that, EPI concentration in tumor in FPA/EPI group was 2.01 times higher than that in free EPI group after 96 h; The concentration of drug in liver treated by FPA/EPI was 5.7-11.6 times, while in heart, kidney, especially in stomach and intestine were much lower than those in free EPI group from 24 to 96 h. Furthermore, blank FPANs showed no apparent acute toxicity at dose up to 125 mg/kg. All results suggested that FPA/EPI showed a promising potential on treating cervical carcinoma and its metastatic hepatocellular carcinoma in future because of the high stability, less toxicity and tumor targeting.
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Antineoplásicos/farmacocinética , Portadores de Fármacos/toxicidade , Epirubicina/farmacocinética , Ácido Fólico/farmacocinética , Glucanos/toxicidade , Nanopartículas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Peso Corporal/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Estabilidade de Medicamentos , Epirubicina/química , Epirubicina/farmacologia , Feminino , Ácido Fólico/química , Glucanos/química , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Nanopartículas/química , Ratos Wistar , Distribuição Tecidual , Neoplasias do Colo do ÚteroRESUMO
This study aimed to characterize the immunopotentiating effects and immune receptors for Coriolus versicolor mushroom polysaccharides (CVP), a Chinese medicinal fungus that exerts anti-tumor activities by enhancing host immunity. Proliferation assays were used to determine whether CVP could activate splenocytes. Flow cytometry analysis and IgM and IgG detection were used to characterize CVP-binding cells. Immune receptors were analyzed in immunoprecipitation and western blot assays. The downstream signaling pathways were identified by western blotting or immunostaining. CVP significantly stimulated the proliferation of mouse splenocytes. Fluorescence-labeled CVP (fl-CVP) selectively stained mouse B cells, but not T cells. CVP induced the production of IgM and IgG1 with or without exogenous IL-4. Membrane Ig (B cell antigen-receptor, BCR) was identified as a CVP-binding protein in immunoprecipitation and western blot experiments. CVP-induced B cell proliferation could be significantly inhibited by anti-mouse immunoglobulin (Ig) blocking antibody (Fab) or in cells from TLR4-mutant mice (C3H/HeJ). Phosphorylation of ERK-1/2 and p38 MAPK were clearly increased in a time-dependent manner, as was the nuclear translocation of the cytosolic NF-κB p65 subunit after CVP stimulation. Together, we demonstrate that CVP can bind and induce B cell activation using membrane Ig and TLR-4 as potential immune receptors. CVP activates mouse B cells through the MAPK and NF-κB signaling pathways.
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Agaricales/química , Linfócitos B/imunologia , Imunoglobulinas/metabolismo , Imunomodulação/efeitos dos fármacos , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fluorescência , Switching de Imunoglobulina/efeitos dos fármacos , Interleucina-2/biossíntese , Cinética , Ativação Linfocitária/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Receptores de Antígenos de Linfócitos B/metabolismo , Baço/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Both iron deficiency and hyperglycemia are highly prevalent globally for pregnant women. Iron supplementation is recommended during pregnancy to control iron deficiency. The purposes of the review are to assess the oxidative effects of iron supplementation and the potential relationship between iron nutrition and gestational diabetes. High doses of iron (~relative to 60 mg or more daily for adult humans) can induce lipid peroxidation in vitro and in animal studies. Pharmaceutical doses of iron supplements (e.g., 10× RDA or more for oral supplements or direct iron supplementation via injection or addition to the cell culture medium) for a short or long duration will induce DNA damage. Higher heme-iron intake or iron status measured by various biomarkers, especially serum ferritin, might contribute to greater risk of gestational diabetes, which may be mediated by iron oxidative stress though lipid oxidation and/or DNA damage. However, information is lacking about the effect of low dose iron supplementation (≤ 60 mg daily) on lipid peroxidation, DNA damage and gestational diabetes. Randomized trials of low-dose iron supplementation (≤ 60 mg daily) for pregnant women are warranted to test the relationship between iron oxidative stress and insulin resistance/gestational diabetes, especially for iron-replete women.
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Dano ao DNA , Diabetes Gestacional/etiologia , Suplementos Nutricionais , Ferro da Dieta/efeitos adversos , Ferro/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Diabetes Gestacional/sangue , Feminino , Ferritinas/sangue , Humanos , Resistência à Insulina , Ferro/farmacologia , Deficiências de Ferro , Ferro da Dieta/administração & dosagem , Estado Nutricional , GravidezRESUMO
BACKGROUND: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for subsequent invasive MRSA infection, particularly in patients admitted for critical care. The purpose of this study was to investigate the risk factors affecting nasal colonization of MRSA in patients admitted to intensive care units (ICU). METHODS: Between August 1, 2011 and June 30, 2012, we screened for MRSA nasal colonization in 350 patients by Real-time PCR within 24 hours of admission by means of swab samples taken from the anterior nares. According to the results of PCR, the patients were divided into 2 groups: the positive group with nasal MRSA colonization and the negative group without nasal MRSA colonization. The 31 (8.86%) patients were MRSA positive. The risk factors evaluated included thirteen variables, which were analyzed by t test for continuous variables and χ(2) test for discrete variables. The variables with significance (P < 0.05) were analyzed with stepwise Logistic regression. RESULTS: There were differences (P < 0.05) in four variables between two groups. The duration of stay in hospital prior to ICU admission in the positive group was (35.7 ± 16.1) days, vs. (4.5 ± 3.1) days in the negative group. The average blood albumin level was (28.4 ± 2.9) g/L in the positive group, vs. (30.5 ± 4.3) g/L in the negative group. Of 31 patients in the positive group, seven had been treated with antibiotics longer than seven days vs. 34 of 319 patients in the negative group. In the positive group, four of 31 patients received treatment with more than two classes of antibiotics prior to admission in ICU, contrasted to 13 of 319 patients in the negative group. Furthermore, stepwise Logistic regression analysis for these four variables indicates that the duration of stay in hospital prior to ICU admission may be an independent risk factor. CONCLUSIONS: MRSA colonization in ICU admission may be related to many factors. The duration of stay in hospital prior to ICU admission is an independent risk factor.
Assuntos
Staphylococcus aureus Resistente à Meticilina/patogenicidade , Cavidade Nasal/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Adulto JovemRESUMO
OBJECTIVE: Type III glycogen storage disease (GSD-III, McKusick 232400), is a rare autosomal recessive disorder, also known as Cori's or Forbe's disease. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (glycogen debrancher enzyme, GDE or amylogluco-sidase, AGL), which is responsible for the debranching of the glycogen molecule during catabolism. The AGL gene is located on chromosome 1p21 and contains 35 exons translated in a monomeric protein product. The clinical manifestations of GSD-III are represented by hepatomegaly, recurrent hypoglycemia, seizures, growth failure, dysmorphism, hyperlipidemia, raised transaminases and creatine kinase concentrations and, in a number of subjects, myopathy and cardiomyopathy. The hepatocellular adenoma, hepatocellular carcinoma, diabetes mellitus and liver fibrosis remain rare events. The diagnosis of debrancher deficiency was established by laboratory tests, electromyography (EMG), and muscle and liver biopsy. METHODS: We studied six GSD-III families after patients or parental consent and the clinical characteristics were documented. Analysis of 33 exons and part exon-intron boundaries of the AGL gene in patients and their parents were carried out by PCR and direct DNA sequencing. RESULTS: The clinical features included hepatomegaly, splenomegaly, recurrent hypoglycemia, hyperlipidemia, growth failure, raised transaminases and acidosis. Administration of epinephrine 2 hours after a carbohydrate meal could provoke normal rise of blood glucose in the affected individuals, but could not evoke any response after overnight fasting. Administration of raw-corn-starch could maintain normoglycemia and improve the disease condition. Mutation analysis for patient 1 was normal. Patient 2 had a compound heterozygote: a C-to-T transition at nucleotide 1294 (come from father, 1294C > T, L 298 L) in exon 8 and a G-to-T transition at nucleotide 4747 (from mother, 4747G > T, E1450X) in exon 34. Patient 3 had a compound heterozygote: a C-to-T transition at nucleotide 1294 (from father, 1294C > T, L 298 L) in exon 8 and a G-to-A transition at nucleotide -10 (from mother, -10G > A) in exon 3. Patient 4 was a homozygote: an insertion of a nucleotide CT into position +65 in exon 35 (4664 ins CT). Patient 5 had a compound heterozygote: a 8 bp deletion at nucleotide 2341 (from father, 2341delGCCATAGA, frameshift mutation) in exon 16 and a G-to-A transition at nucleotide 1559 (from mother, 1559G > A, R 387 Q) in exon 10. Patient 6 had a compound heterozygote: a T-to-G transition at nucleotide 1686 (from mother, 1686T > G, Y429 X) in exon 12 and a G-to-A transition at nucleotide 3742 (from father, 3742G > A, G 1115 R) in exon 26. CONCLUSION: GSD-III patients have variable phenotypic characteristics. Administration of raw-corn-starch can effectively improve the disease outcome. We identified 8 new mutations on AGL gene through nucleotide sequence analysis.