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BACKGROUND: Systemic inflammation is a potent contributor to increased seizure susceptibility. However, information regarding the effects of systemic inflammation on cerebral vascular integrity that influence neuron excitability is scarce. Necroptosis is closely associated with inflammation in various neurological diseases. In this study, necroptosis was hypothesized to be involved in the mechanism underlying sepsis-associated neuronal excitability in the cerebrovascular components (e.g., endothelia cells). METHODS: Lipopolysaccharide (LPS) was used to induce systemic inflammation. Kainic acid intraperitoneal injection was used to measure the susceptibility of the mice to seizure. The pharmacological inhibitors C87 and GSK872 were used to block the signaling of TNFα receptors and necroptosis. In order to determine the features of the sepsis-associated response in the cerebral vasculature and CNS, brain tissues of mice were obtained for assays of the necroptosis-related protein expression, and for immunofluorescence staining to identify morphological changes in the endothelia and glia. In addition, microdialysis assay was used to assess the changes in extracellular potassium and glutamate levels in the brain. RESULTS: Some noteworthy findings, such as increased seizure susceptibility and brain endothelial necroptosis, Kir4.1 dysfunction, and microglia activation were observed in mice following LPS injection. C87 treatment, a TNFα receptor inhibitor, showed considerable attenuation of increased kainic acid-induced seizure susceptibility, endothelial cell necroptosis, microglia activation and restoration of Kir4.1 protein expression in LPS-treated mice. Treatment with GSK872, a RIP3 inhibitor, such as C87, showed similar effects on these changes following LPS injection. CONCLUSIONS: The findings of this study showed that TNFα-mediated necroptosis induced cerebrovascular endothelial damage, neuroinflammation and astrocyte Kir4.1 dysregulation, which may coalesce to contribute to the increased seizure susceptibility in LPS-treated mice. Pharmacologic inhibition targeting this necroptosis pathway may provide a promising therapeutic approach to the reduction of sepsis-associated brain endothelia cell injury, astrocyte ion channel dysfunction, and subsequent neuronal excitability.
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Necroptose , Fator de Necrose Tumoral alfa , Animais , Encéfalo/metabolismo , Células Endoteliais/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Convulsões/induzido quimicamente , Fator de Necrose Tumoral alfa/metabolismoRESUMO
STUDY OBJECTIVE: Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. Bullae are special skin manifestations of NF. This study was conducted to analyze the differences between different types of bullae of limbs with NF for providing the information to emergency treatment. METHODS: From April 2015 to August 2018, patients were initially enrolled based on surgical confirmation of limbs with NF. According to the presence of different bullae types, patients were divided into no bullae group (Group N), serous-filled bullae group (Group S), and hemorrhagic bullae group (Group H). Data such as demographics, clinical outcomes, microbiological results, presenting symptoms/signs, and laboratory findings were compared among these groups. RESULTS: In total, 187 patients were collected, with 111 (59.4%) patients in Group N, 35 (18.7%) in Group S, and 41 (21.9%) in Group H. Group H had the highest incidence of amputation, required intensive care unit care, and most patients infected with Vibrio species. In Group N, more patients were infected with Staphylococcus spp. than Group H. In Group S, more patients were infected with ß-hemolytic Streptococcus than Group H. Patients with bacteremia, shock, skin necrosis, anemia, and longer prothrombin time constituted higher proportions in Group H and S than in Group N. CONCLUSIONS: In southern Taiwan, patients with NF accompanied by hemorrhagic bullae appear to have more bacteremia, Vibrio infection, septic shock, and risk for amputation. If the physicians at the emergency department can detect for the early signs of NF as soon as possible, and more patient's life and limbs may be saved.
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Vesícula , Fasciite Necrosante , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/estatística & dados numéricos , Bacteriemia/epidemiologia , Vesícula/complicações , Vesícula/epidemiologia , Vesícula/terapia , Fasciite Necrosante/complicações , Fasciite Necrosante/epidemiologia , Fasciite Necrosante/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Séptico/epidemiologia , Infecções dos Tecidos Moles/complicações , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/terapia , TaiwanRESUMO
It was found that 4-hydroxy-2-butenoic ester (11) could not react with 3,4-dihydro-isoquinoline (4a). Individual addition reactions of γ-mercapto-α,ß-unsaturated esters (18) and -unsaturated amide (19) with 3,4-dihydroisoquinolines (4) were carried out under appropriate conditions to provide the corresponding thiazolo[2,3-α]isoquinoline derivatives with good yields (up to 87%) and significant diastereomeric selectivity. The mechanism of the crucial reaction was discussed.
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BACKGROUND: Research indicates that sepsis increases the risk of developing cognitive impairment. After systemic inflammation, a corresponding activation of microglia is rapidly induced in the brain, and multiple neurotoxic factors, including inflammatory mediators (e.g., cytokines) and reactive oxygen species (e.g., superoxide), are also released that contribute to neuronal injury. NADPH oxidase (NOX) enzymes play a vital role in microglial activation through the generation of superoxide anions. We hypothesized that NOX isoforms, particularly NOX2, could exhibit remarkable abilities in developing cognitive deficits induced by systemic inflammation. METHODS: Mice with deficits of NOX2 organizer p47phox (p47phox-/-) and wild-type (WT) mice treated with the NOX inhibitor diphenyleneiodonium (DPI) were used in this study. Intraperitoneal lipopolysaccharide (LPS) injection was used to induce systemic inflammation. Spatial learning and memory were compared among treatment groups using the radial arm maze task. Brain tissues were collected for evaluating the transcript levels of proinflammatory cytokines, whereas immunofluorescence staining and immunoblotting were conducted to determine the percentage of activated glia (microglia and astroglia) and damaged neurons and the expression of synaptic proteins and BDNF. RESULTS: Cognitive impairment induced by systemic inflammation was significantly attenuated in the p47phox-/- mice compared to that in the WT mice. The p47phox-/- mice exhibited reduced microglial and astroglial activation and neuronal damage and attenuated the induction of multiple proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and CCL2. Similar to that observed in the p47phox-/- mice, the administration of DPI significantly attenuated the cognitive impairment, reduced the glial activation and brain cytokine concentrations, and restored the expression of postsynaptic proteins (PSD-95) and BDNF in neurons and astrocytes, compared to those in the vehicle-treated controls within 10 days after LPS injection. CONCLUSIONS: This study clearly demonstrates that NOX2 contributes to glial activation with subsequent reduction in the expression of BDNF, synaptic dysfunction, and cognitive deficits after systemic inflammation in an LPS-injected mouse model. Our results provide evidence that NOX2 might be a promising pharmacological target that could be used to protect against synaptic dysregulation and cognitive impairment following systemic inflammation.
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Disfunção Cognitiva , Inflamação , NADPH Oxidase 2 , Oniocompostos , Animais , Doença Crônica , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Inflamação/complicações , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , NADPH Oxidase 2/metabolismo , Oniocompostos/farmacologia , Oniocompostos/uso terapêutico , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Systemic inflammation associated with sepsis can induce neuronal hyperexcitability, leading to enhanced seizure predisposition and occurrence. Brain microglia are rapidly activated in response to systemic inflammation and, in this activated state, release multiple cytokines and signaling factors that amplify the inflammatory response and increase neuronal excitability. NADPH oxidase (NOX) enzymes promote microglial activation through the generation of reactive oxygen species (ROS), such as superoxide anion. We hypothesized that NOX isoforms, particularly NOX2, are potential targets for prevention of sepsis-associated seizures. METHODS: To reduce NADPH oxidase 2-derived ROS production, mice with deficits of NOX regulatory subunit/NOX2 organizer p47phox (p47phox-/-) or NOX2 major subunit gp91phox (gp91phox-/-) were used or the NOX2-selective inhibitor diphenyleneiodonium (DPI) was used to treat wild-type (WT) mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS). Seizure susceptibility was compared among mouse groups in response to intraperitoneal injection of pentylenetetrazole (PTZ). Brain tissues were assayed for proinflammatory gene and protein expression, and immunofluorescence staining was used to estimate the proportion of activated microglia. RESULTS: Increased susceptibility to PTZ-induced seizures following sepsis was significantly attenuated in gp91phox-/- and p47phox-/- mice compared with WT mice. Both gp91phox-/- and p47phox-/- mice exhibited reduced microglia activation and lower brain induction of multiple proconvulsive cytokines, including TNFα, IL-1ß, IL-6, and CCL2, compared with WT mice. Administration of DPI following LPS injection significantly attenuated the increased susceptibility to PTZ-induced seizures and reduced both microglia activation and brain proconvulsive cytokine concentrations compared with vehicle-treated controls. DPI also inhibited the upregulation of gp91phox transcripts following LPS injection. CONCLUSIONS: Our results indicate that NADPH oxidases contribute to the development of increased seizure susceptibility in mice after sepsis. Pharmacologic inhibition of NOX may be a promising therapeutic approach to reducing sepsis-associated neuroinflammation, neuronal hyperexcitability, and seizures.
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Sistemas de Liberação de Medicamentos/métodos , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Convulsões/enzimologia , Convulsões/prevenção & controle , Sepse/enzimologia , Animais , Células Cultivadas , Inibidores Enzimáticos/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 2/antagonistas & inibidores , NADPH Oxidase 2/metabolismo , Pentilenotetrazol/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Convulsões/induzido quimicamente , Sepse/induzido quimicamente , Sepse/tratamento farmacológicoRESUMO
Red Ca0.99Al(1-4δ/3-x)Si(1+δ+x)N(3-x)C(x):Eu(2+)0.01 (δ = 0.345; x = 0-0.2) nitride phosphors exhibit a blue-shifted emission with increased eye sensitivity function and excellent thermal stability. The variations in the photoluminescence in the Ca0.99Al(1-4δ/3-x)Si(1+δ+x)N(3-x)C(x):Eu(2+)0.01 (δ = 0.345; x = 0-0.2) system are thoroughly investigated. The enhanced emission energy and the improved thermal stability with increasing x are dominated by the second-sphere shrinkage effect via the substitution of small Si(4+) for large Al(3+) with simultaneous charge compensation. Related proofs of the second-sphere shrinkage effect control for photoluminescence are confirmed via high-resolution neutron powder diffraction, EXAFS, and (29)Si solid-state NMR techniques.
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Background: Mastitis is a common disorder among postpartum women. The discomfort and pain caused by mastitis may lead to the discontinuation of breastfeeding. Large-scale epidemiological studies examining mastitis are limited. Accordingly, the present study used a nationwide population-based database to collect information about all postpartum women in Taiwan to determine the incidence of and related factors for mastitis. Materials and Methods: This retrospective population-based study used the National Health Insurance Research Database to collect records of patients with mastitis during 2008-2017 and then linked the collected data to the Taiwan Birth Registry. We included women diagnosed as having lactational mastitis within 6 months of delivery. A multivariable logistic regression model was used to compare the risk of mastitis between parity in multiparous women. Results: We identified 1,686,167 deliveries in 1,204,544 women. 19,794 women with 20,163 deliveries had a medical claim for mastitis. The incidence proportion of mastitis for 6 months postpartum was â¼1.19% and highest during the first month after delivery. Multivariable logistic regression revealed that multiparous women with a history of mastitis were likely to experience mastitis again after subsequent deliveries (adjusted odds ratio = 5.86; 95% confidence interval = 5.21-6.58). The Kaplan-Meier curve indicated that primiparous women had a higher risk of mastitis than did multiparous women (log-rank test, p < 0.001). Conclusion: Mastitis generally occurred during the first month postpartum, and primiparous women had a higher risk of mastitis than did multiparous women. Furthermore, multiparous women with a history of mastitis had a 5.86-fold increased risk of recurrence during subsequent deliveries.
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Mastite , Período Pós-Parto , Gravidez , Feminino , Humanos , Incidência , Estudos Retrospectivos , Taiwan/epidemiologia , Mastite/epidemiologiaRESUMO
INTRODUCTION: Hot flashes, the most bothering symptom of menopause, are linked to a metabolic inflammation. Due to estrogen deficiency in menopause, dysbiosis is observed. The intestinal barrier affects the interaction of microbiota in healthy or unhealthy individuals. This study investigates the relationship between hot flashes and gut permeability in postmenopausal women. PARTICIPANTS AND DESIGN: In this cross-sectional study, we divided 289 women, aged 40-65 years, into four groups based on their hot-flash severity: HF0: never experienced hot flashes; HFm: mild hot flashes; HFM: moderate hot flashes; HFS: severe hot flashes. The measured variables included the clinical parameters; hot flashes experience; fasting plasma levels of zonulin, fatty acid binding protein 2 (FABP2), endotoxin, and cytokines/chemokines. We used multiple linear regression analysis to evaluate the relationship between hot flashes and the previously mentioned gut barrier proteins. SETTINGS: The study was performed in a hospital medical center. RESULTS: The hot flashes had a positive tendency toward increased levels of circulating FABP2 (P-trend = 0.001), endotoxin (P-trend = 0.031), high-sensitivity C-reactive protein (hs-CRP) (P-trend = 0.033), tumor necrosis factor alpha (TNF-α) (P-trend = 0.017), and interferon-inducible protein-10 (IP10) (P-trend = 0.021). Spearman's correlation analysis revealed significant correlations of FABP2 with endotoxin, TNF-α, monocyte chemoattractant protein-1, IP10, and hs-CRP in the 289 postmenopausal women included in this study. Linear regression analysis revealed that hot-flash severity had significant assoiciations with FABP2 (P-trend = 0.002), but not with zonulin. After adjusting for body mass index, age, and menopause duration, multivariate linear regression analysis revealed the differences between HFs (% difference (95% confidence interval), 22.36 (8.04, 38.59), P = 0.01) and HF0 groups in terms of FABP2 levels. CONCLUSIONS: This study shows that hot flashes are significantly associated with FABP2 levels in postmenopausal women. It suggests that severe hot flashes are linked to an increase in intestinal barrier permeability and low-grade systemic inflammation.
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Proteína C-Reativa , Fogachos , Feminino , Humanos , Proteína C-Reativa/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CXCL10/metabolismo , Estudos Transversais , Endotoxinas , Estrogênios , Proteínas de Ligação a Ácido Graxo , Inflamação , Interferons/metabolismo , Menopausa , Pós-Menopausa , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Salmonella meningitis remains a threat to children below two years of age in both developing and developed countries. However, information on such infections has not been well characterized. We analyzed data related to twelve years of experience in order to clarify the comprehensive features of Salmonella meningitis in our patients, including admission characteristics, acute complications, and long-term outcome. METHODS: The records of patients with spontaneous Salmonella meningitis from 1982 to 1994 were retrospectively reviewed. The long-term outcome was prospectively determined for survivors at school age by the developmental milestones reported by their parents and detailed neurological evaluation along with intelligence, hearing, visual, speech and language assessments. RESULTS: Of the twenty-four patients, seizures were noted in fifteen (63%) before admission and thirteen (54%) during hospitalization. Acute complications mainly included hydrocephalus (50%), subdural collection (42%), cerebral infarction (33%), ventriculitis (25%), empyema (13%), intracranial abscess (8%), and cranial nerve palsy (8%). Three patients (13%) died during the acute phase of Salmonella meningitis. The twenty-one survivors, on whom we followed up at school age, have sequelae consisting of language disorder (52%), motor disability (48%), intelligence quotient < 80 (43%), epilepsy (33%), sensorineural hearing loss (17%), visual deficits (10%), abducens nerve palsy (5%), microcephaly (5%), and hydrocephalus (5%). Overall, good outcome was noted in six (28.6%) of twenty-one survivors, mild sequelae in three (14.2%), moderate in six (28.6%), and severe in six (28.6%). CONCLUSION: Salmonella meningitis in neonates and infants had a wide spectrum of morbidity and acute complications, leading to a complicated hospital course and subsequently a high prevalence of permanent adverse outcome. Thus, early recognition of acute complications of Salmonella meningitis and a follow-up plan for early developmental assessment of survivors are vital.
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Meningites Bacterianas/complicações , Infecções por Salmonella/complicações , Infecções por Salmonella/mortalidade , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Meningites Bacterianas/mortalidade , Estudos Retrospectivos , Salmonella/classificação , Salmonella/isolamento & purificação , Salmonella/fisiologia , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Sobreviventes/estatística & dados numéricos , Taiwan/epidemiologiaRESUMO
INTRODUCTION: Studies on the association between adiponectin and leptin and anxiety and depression among postmenopausal women are limited. Therefore, the present study specifically evaluates the mutual relationships between adiponectin and leptin and anxiety and depression in postmenopausal women. PARTICIPANTS AND DESIGN: In this cross-sectional study, a total of 190 women aged 40-65 years were enrolled. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAM-A). Fasting specimens were collected to measure sex hormone, glucose, insulin, and adipokine levels. Multiple linear regression analysis was performed to evaluate the associations between depression and anxiety and adipocyte-derived hormones. SETTINGS: The study was performed in a hospital medical center. RESULTS: Among 190 enrolled postmenopausal women, Spearman's rank correlation analysis revealed significant correlations between CES-D and HAM-A (r = 0.715, P < 0.0001), between CES-D and adiponectin (p = 0.009) and leptin (p = 0.015), and between HAM-A and adiponectin (p = 0.01) and leptin (p = 0.001). The subjects with CES-D ≥ 16 and with HAM-A ≥ 18 had higher adiponectin levels than those with CES-D < 16 and HAM-A < 18, respectively. After adjusting for age, body mass index, exercise, alanine amino transferase and parameters of lipid profiles, Log adiponectin levels were found to be significantly associated with both CES-D and HAM-A, and Log leptin levels were only significantly associated with HAM-A. CONCLUSIONS: The data show that adiponectin and leptin levels are significantly associated with depression and anxiety symptoms. These results suggest that higher adiponectin and lower leptin levels may serve as potential markers related to anxiety and mood in postmenopausal women. More future research that is designed to deal with the important confounders (e.g., population heterogeneity) is needed to investigate comprehensively on these associations.
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Ansiedade/metabolismo , Depressão/metabolismo , Insulina/genética , Obesidade/metabolismo , Pós-Menopausa/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adipocinas/genética , Adiponectina/genética , Adulto , Idoso , Ansiedade/patologia , Índice de Massa Corporal , Estudos Transversais , Depressão/patologia , Feminino , Humanos , Resistência à Insulina/genética , Leptina/genética , Obesidade/genética , Obesidade/patologiaRESUMO
Beyond fertility, follicle-stimulating hormone (FSH) may exert action on adipocytes, which are the major source of adiponectin and leptin, linking to insulin resistance. Therefore, we evaluated the relationships between FSH and adipocyte-derived hormones. This cross-sectional study enrolled postmenopausal women aged 40-65 years. The variables measured in this study included clinical parameters, fasting levels of sex hormones, glucose, insulin, and adipokines. A total of 261 women without breast cancer, 88 women with breast cancer receiving tamoxifen, and 59 women with breast cancer receiving additional gonadotropin-releasing hormone analogs were enrolled in this study. Significant differences in the levels of adiponectin, leptin, and FSH were observed between the non-breast cancer group and the breast cancer groups. Spearman's rank test revealed significant associations of FSH with either body mass index (BMI) or homeostatic model assessment of insulin resistance (HOMA-IR) values in the non-breast cancer group. After adjusting for BMI, age, and menopause duration, FSH levels were significantly associated with adiponectin (p < 0.001) and the leptin-to-adiponectin ratio (p = 0.008) in the non-breast cancer group, but they were only significantly associated with adiponectin (p = 0.001) in the breast cancer group receiving tamoxifen. Our data show that FSH levels are independently associated with adiponectin levels in postmenopausal women, suggesting that adiponectin may link FSH to metabolic relationships in postmenopausal female.
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Early life stress (ELS) can affect brain development and increase lifetime prevalence of psychiatric illnesses. However, the effective therapeutic interventions to ameliorate the deleterious effects of ELS have not yet been well established. Here, we confirmed that maternal separation (MS) for 3â¯h daily between postnatal days 2-14, a frequently used experimental model of ELS, resulted in early expression of adult-like fear memory retention in male infant rats. Administration of a probiotic formulation, Lacidofil® (95% Lactobacillus rhamnosus R0011 and 5% Lactobacillus helveticus R0052), during the separation period, prevented the precocious transition to adult-like fear memory retention in MS infant rats. Consonant with this effect, probiotic treatment also ameliorated the MS-induced increases in anxiety-like behavior as measured by the elevated plus maze and the light-dark box tests. In addition, probiotic treatment reduced MS-induced increases in neuronal activation and brain-derived neurotrophic factor protein levels in the basolateral nucleus of amygdala (BLA) after auditory fear conditioning. Furthermore, we found that probiotic treatment significantly rescued the heightened hypothalamic-pituitary-adrenal (HPA) axis response to restraint stress in MS infant rats. Taken together, these findings suggest that probiotics can restore normal developmental trajectories of fear memory retention in MS infant rats, at least in part by normalizing HPA axis abnormalities, and that the BLA serves as a critical node to mediate these interventions. Thus, we offer a potential therapeutic intervention to protect children against the harmful effects of ELS.
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Medo/efeitos dos fármacos , Medo/fisiologia , Privação Materna , Memória/efeitos dos fármacos , Memória/fisiologia , Probióticos/administração & dosagem , Animais , Animais Recém-Nascidos , Medo/psicologia , Feminino , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
INTRODUCTION: Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women. PARTICIPANTS AND DESIGN: In this cross-sectional study, a total of 151 women aged 45-60 years were stratified into one of three groups according to hot-flash status over the past three months: never experienced hot flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, fasting levels of circulating glucose, lipid profiles, plasma insulin, and adipocyte-derived hormones. Multiple linear regression analysis was used to evaluate the associations of hot flashes with adipocyte-derived hormones, and with insulin resistance. SETTINGS: The study was performed in a hospital medical center. RESULTS: The mean (standard deviation) of body-mass index was 22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S, respectively. Women in Group S displayed statistically significantly higher levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin than those in Groups M and N. Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with higher leptin levels, lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate linear regression analysis revealed that hot-flash severity was strongly associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence interval, 31.00-90.64; p < 0.001). The association between hot flashes and HOMA-IR index was attenuated after adjusting for leptin or adiponectin and was no longer significant after simultaneously adjusting for leptin and adiponectin. CONCLUSION: The present study provides evidence that hot flashes are associated with insulin resistance in postmenopausal women. It further suggests that hot flash association with insulin resistance is dependent on the combination of leptin and adiponectin variables.
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Adiponectina/sangue , Fogachos/sangue , Fogachos/metabolismo , Resistência à Insulina , Leptina/sangue , Pós-Menopausa/sangue , Pós-Menopausa/metabolismo , Adipócitos/metabolismo , Feminino , Fogachos/patologia , Humanos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Sleep disturbance is very common in menopausal women and poor sleep quality has been linked to systemic inflammation. However, the impact of poor sleep quality on health outcomes of menopausal women remains unclear. This study evaluated the relationships between sleep quality and inflammation in menopausal women. PARTICIPANTS AND DESIGN: This cross-sectional study enrolled 281 healthy women aged 45 to 60 years. The Pittsburgh Sleep Quality Index (PSQI) was used to measure quality of sleep. Multiplex assays were used to measure the levels of 9 cytokines in morning fasting plasma samples. Other variables measured in this study included clinical characteristics and high-sensitivity C-reactive protein (hs-CRP). SETTING: The study was performed at a medical center. RESULTS: The 281 participants comprised 79 (28%) perimenopausal women and 202 (72%) postmenopausal women. Global PSQI scores were positively correlated with plasma hs-CRP levels (P = 0.012) and were marginally associated with interferon gamma-inducible protein-10 (IP10), interleukin 6 (IL6), and macrophage inflammatory protein-1beta (MIP-1ß) levels. After adjusting for age, body mass index, menopause duration, and follicle stimulating hormone, multiple linear regression analysis revealed that high PSQI scores and sleep efficiency < 65% were associated with elevated plasma levels of hs-CRP, IP10, and IL6. In addition, sleep duration < 5 hours was associated with high hs-CRP levels. CONCLUSION: Our data show that poor sleep quality and low sleep efficiency are associated with elevated levels of circulating inflammatory factors IP10, IL6 and hs-CRP and that short sleep duration is associated with high levels of hs-CRP in menopausal women. These findings provide novel evidence that poor sleep quality is linked to low-grade systemic inflammation in menopausal women.
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Proteína C-Reativa/metabolismo , Quimiocina CXCL10/sangue , Interleucina-6/sangue , Menopausa/sangue , Sono/fisiologia , Quimiocina CCL2/sangue , Quimiocina CCL4/sangue , Estudos Transversais , Humanos , Interleucina-17/sangue , Interleucina-8/sangue , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Hot flashes have been postulated to be linked to systemic inflammation. This study aimed to investigate the relationship between hot flashes, pro-inflammatory factors, and leukocytes in healthy, non-obese postmenopausal women. PARTICIPANTS AND DESIGN: In this cross-sectional study, a total of 202 women aged 45-60 years were stratified into one of four groups according to their hot-flash status: never experienced hot flashes (Group N), mild hot flashes (Group m), moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, leukocytes, and fasting plasma levels of nine circulating cytokines/chemokines measured by using multiplex assays. Multiple linear regression analysis was used to evaluate the associations of hot flashes with these pro-inflammatory factors. SETTINGS: The study was performed in a hospital medical center. RESULTS: The mean values of leukocyte number were not different between these four groups. The hot flash status had a positive tendency toward increased levels of circulating IL-6 (P-trend = 0.049), IL-8 (P-trend < 0.001), TNF-α (P-trend = 0.008), and MIP1ß (P-trend = 0.04). Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with IL-8 (P-trend < 0.001) and TNFα (P-trend = 0.007) among these nine cytokines/chemokines after adjustment for age, menopausal duration, BMI and FSH. Multivariate analysis further revealed that severe hot flashes were strongly associated with a higher IL-8 (% difference, 37.19%; 95% confidence interval, 14.98,63.69; P < 0.001) and TNFα (51.27%; 6.64,114.57; P < 0.05). CONCLUSION: The present study provides evidence that hot flashes are associated with circulating IL-8 and TNF-α in healthy postmenopausal women. It suggests that hot flashes might be related to low-grade systemic inflammation.
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Fogachos/sangue , Interleucina-8/sangue , Pós-Menopausa , Fator de Necrose Tumoral alfa/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The specific properties of gold nanoparticles (AuNPs) make them a novel class of photothermal agents that can induce cancer cell damage and even death through the conversion of optical energy to thermal energy. Most relevant studies have focused on increasing the precision of cell targeting, improving the efficacy of energy transfer, and exploring additional functions. Nevertheless, most cells can uptake nanosized particles through nonspecific endocytosis; therefore, before hyperthermia via AuNPs can be applied for clinical use, it is important to understand the adverse optical-thermal effects of AuNPs on nontargeted cells. However, few studies have investigated the thermal effects induced by pulsed laser-activated AuNPs on nearby healthy cells due to nonspecific treatment. The aim of this study is to evaluate the photothermal effects induced by AuNPs plus a pulsed laser on MG63, an osteoblast-like cell line, specifically examining the effects on cell morphology, viability, death program, and differentiation. The cells were treated with media containing 50 nm AuNPs at a concentration of 5 ppm for 1 hour. Cultured cells were then exposed to irradiation at 60 mW/cm(2) and 80 mW/cm(2) by a Nd:YAG laser (532 nm wavelength). We observed that the cytoskeletons of MG63 cells treated with bare AuNPs followed by pulsed laser irradiation were damaged, and these cells had few bubbles on the cell membrane compared with those that were not treated (control) or were treated with AuNPs or the laser alone. There were no significant differences between the AuNPs plus laser treatment group and the other groups in terms of cell viability, death program analysis results, or alkaline phosphatase and calcium accumulation during culture for up to 21 days. However, the calcium deposit areas in the cells treated with AuNPs plus laser were larger than those in other groups during the early culture period.
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Apoptose/efeitos da radiação , Ouro/química , Hipertermia Induzida , Lasers de Estado Sólido , Nanopartículas Metálicas/química , Osteoblastos/citologia , Osteoblastos/efeitos da radiação , Osteogênese/efeitos da radiação , Fosfatase Alcalina/metabolismo , Calcificação Fisiológica/efeitos da radiação , Cálcio/metabolismo , Linhagem Celular Tumoral , Forma Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Humanos , Microscopia Confocal , Osteoblastos/efeitos dos fármacos , Osteoblastos/enzimologia , TemperaturaAssuntos
Endometriose/complicações , Ciática/etiologia , Adulto , Endometriose/cirurgia , Feminino , Humanos , MenstruaçãoRESUMO
BACKGROUND: L-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and L-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappaB (NF-kappaB) were also investigated. METHODS: Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 microm), lipopolysaccharide plus hemin (5, 50, or 500 microm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 microm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed. RESULTS: Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-kappaB activation, CAT-2 expression, and L-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-kappaB activation, CAT-2 expression, and L-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin. CONCLUSIONS: HO-1 induction significantly inhibited CAT-2 expression and L-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-kappaB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and L-arginine transport.