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1.
Inflammopharmacology ; 32(2): 1147-1157, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38180676

RESUMO

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.


Assuntos
Escitalopram , Lipopolissacarídeos , Camundongos , Animais , Masculino , Lipopolissacarídeos/farmacologia , Depressão/tratamento farmacológico , Depressão/metabolismo , Ácido Ascórbico/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Vitaminas , Adjuvantes Imunológicos , Vitamina D , Modelos Animais
2.
ScientificWorldJournal ; 2023: 8876254, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37766862

RESUMO

Objective: This cross-sectional study aimed at investigating the influence of sociodemographic factors on physical activity among Syrian and Iraqi refugees in Jordan. In addition, it sought to determine the predictive ability of self-efficacy and mood in relation to the level of physical activity in this population. Methods: A convenient sample of refugees residing in Jordanian cities was collected. Participants completed a self-administered questionnaire pack consisting of a demographic data sheet, a physical activity level questionnaire, the Brunel Mood Scale, and the General Self-Efficacy Scale. Descriptive analysis was used to analyze demographic details, while the chi-square test examined the association between physical activity and demographic factors. The independent t-test assessed differences in self-efficacy and mood subscales in relation to physical activity. Logistic regression analysis was employed to identify potential predictors of the two categories of physical activity. Results: Most participants reported low levels of physical activity. The frequency of moderate-to-high physical activity was higher in male participants, those with higher education, better health, and higher income. Compared to participants of low physical activity, those in the moderate-to-high physical activity category expressed significantly higher mean score of self-efficacy but lower mean scores of tension, depression, anger, vigor, fatigue, and confusion, indicating better mood. The logistic regression analysis for physical activity indicated that the model was significant for education, income, good health perception, self-efficacy, and one mood subscale (vigor), with these variables collectively accounting for 11-18% of the variance (P value <0.001). Conclusion: The higher physical activity level is significantly associated with being male, higher education, higher income, better health, higher self-efficacy, and increased vigor. These findings highlight the importance of considering sociodemographic factors and psychological aspects, such as self-efficacy and mood, when addressing physical activity among refugees in Jordan.

3.
BMC Health Serv Res ; 22(1): 1481, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471368

RESUMO

BACKGROUND AND AIM: Fear of coronavirus disease 2019 (COVID-19) and its complications may result in stigmatization of individuals who may carry the virus. This is of special concern to healthcare workers who tolerate additional physical and emotional stress at times of pandemic. The aims of this study are to (1) develop and validate the COVID-19 Stigma Scale (COVISS-HCWs) survey; and (2) investigate the experience of stigma among healthcare workers possibly dealing with COVID-19 patients in five major public hospitals in Damascus, Syria. METHODS: We divided the sample into two parts and then underwent EFA on the first 350 participants, dividing the 14 questions into two dimensions. Furthermore, CFA was conducted on the other 350 participants to confirm how correctly a hypothesized model matched the factor structure by EFA, as described above. Moreover, the coefficient of determination (R2) and item-scale correlations (standardized factor loading) were estimated to establish the acceptability of the final structure of the COVISS-HCWs. Through a cross-sectional study, a convenience sample of 700 healthcare workers participated in a self-administered questionnaire containing a section for demographic variables and another for newly designed COVISS-HCWs. The scale comprises 14 adapted and novel items that measure two subscales: feelings of perceived harm and inferiority, and avoidance. Descriptive statistics, reliability, and validity were evaluated. RESULTS: The 14 COVISS-HCWs items were reduced to 11 items with a high Cronbach's α of 0.909. A significant correlation was observed between the responses to each COVISS-HCWs item and the corresponding subscale, and between each subscale and the overall scale. Feeling stigmatized was reported by 9.86% of the participants. Younger age, low socioeconomic status, and higher intensity of contact with COVID-19 patients significantly correlated with higher stigmatization. CONCLUSIONS: The novel COVISS-HCWs is a reliable and valid tool to evaluate stigma among healthcare workers during the COVID-19 pandemic. The Stigma prevalence among healthcare workers was 9.86%. Therefore, this must be addressed to prevent possible psychosocial and public health repercussions.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Reprodutibilidade dos Testes , Estudos Transversais , Pessoal de Saúde/psicologia
4.
Curr Res Toxicol ; 5: 100127, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767028

RESUMO

This study scrutinizes the effects of simulated microgravity on the antioxidant and cytotoxic potential, along with the phytochemical content of wheatgrass (Triticum aestivum Linn). To imitate microgravity, wheatgrass seeds were germinated in a 3D-clinostat at different rotations per minute (5, 10, 15, and 20 rpm), together with terrestrial gravity control, over 10 days. After germination, the methanolic extracts were analyzed using UPLC-Triple Quad LCMS for their phytochemical composition and tested for their hydrogen peroxide, nitric oxide, and DPPH scavenging activities. The cytotoxic effects of these extracts were evaluated against normal skin fibroblasts, normal breast cells (MCF-10), and breast cancer cells (MCF-7 and MDA-231). The findings showed an extended root growth in wheatgrass germinated under microgravity (WGM) compared to under gravity (WGG). Additionally, WGM extracts demonstrated increased H2O2-, NO-, and DPPH-scavenging activities and a higher content of polyphenols and flavonoids than WGG extracts. These effects were amplified with an increase in clinostat rotations. Moreover, WGM extracts were found to contain a unique set of bioactive compounds (compounds that were detected in the microgravity-germinated wheatgrass but were either absent or present in lower concentrations in wheatgrass germinated under standard gravity conditions.), including pyridoxine, apigenin, and tocopherol, among others, which were absent in WGG. The UPLC-Triple Quad LCMS analysis revealed these unique bioactive compounds in WGM. Notably, WGM extracts showed enhanced cytotoxic effects against normal skin fibroblasts, normal MCF-10, MCF-7, and breast cancer MDA-231 cell lines, with increased cytotoxicity correlating with the number of clinostat rotations. Particularly, WGM extract (at 20 rpm) demonstrated significantly stronger cytotoxicity against MCF-7 breast cancer cells. Further in-depth gene expression analysis of MCF-7 cells exposed to WGM revealed a significant downregulation of genes integral to breast cancer pathways, tyrosine kinase signaling, and DNA repair, complemented by upregulation of certain cell survival and cytotoxic genes. These alterations in genetic pathways associated with cell survival, hormone responses, and cancer progression may elucidate the enhanced cytotoxicity observed in WGM extracts. Our findings underscore the potential of microgravity as a tool to enhance the cytotoxic capabilities of wheatgrass against cancer cell lines, presenting a promising direction for future research in the field of space biology and its implications for terrestrial health.

5.
Obesity (Silver Spring) ; 31 Suppl 1: 57-62, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36203273

RESUMO

OBJECTIVE: Concerns have been raised regarding the impact of time-restricted eating (TRE) on sex hormones in females. This study examined how TRE affects sex steroids in premenopausal and postmenopausal females. METHODS: This is a secondary analysis of an 8-week TRE study (4- to 6-hour eating window) conducted in adults with obesity. Men and perimenopausal females were excluded. Females were classified into two groups based on menstrual status: premenopausal (n = 12) or postmenopausal (n = 11). RESULTS: After 8 weeks, body weight decreased in premenopausal females (-3% ± 2%) and postmenopausal females (-4% ± 2%) (main effect of time, p < 0.001), with no difference between groups (no group × time interaction). Circulating levels of testosterone, androstenedione, and sex hormone binding globulin (SHBG) did not change in either group (no group × time interaction). Dehydroepiandrosterone (DHEA) concentrations decreased (p < 0.05) in premenopausal (-14% ± 32%) and postmenopausal females (-13% ± 34%; main effect of time, p = 0.03), with no difference between groups. Estradiol, estrone, and progesterone were measured only in postmenopausal females, and they remained unchanged. CONCLUSIONS: In premenopausal females, androgens and SHBG remained unchanged during TRE, whereas DHEA decreased. In postmenopausal females, estrogens, progesterone, androgens, and SHBG did not change, but DHEA was reduced.


Assuntos
Jejum Intermitente , Pós-Menopausa , Progesterona , Adulto , Feminino , Humanos , Androgênios , Desidroepiandrosterona , Estradiol , Hormônios Esteroides Gonadais , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona
6.
Nutrients ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200748

RESUMO

This study aimed at developing a valid culture-sensitive quantitative food frequency questionnaire (FFQ) for Qatari adults. A convenient sample of healthy Qataris (n = 107) were recruited from family members of Qatar University students. The Diet History Questionnaire II of the US National Cancer Institute was translated to Arabic language, back-translated to English, pilot tested, and then modified accordingly to be used in Qatari setting. Participants were asked to complete the translated version of the FFQ. This FFQ was then validated against three 24 h diet recall (24 hDR) including a weekend day. Participants were asked to complete the FFQ again after one-month period to measure its repeatability. Dietary data were analyzed using the dietary analysis software ESHA. The validity and reliability of FFQ were assessed by comparing the median intake of nutrients and foods and by calculating the Pearson correlation coefficients. The median nutrient intakes assessed by the second FFQ were higher than that reported in the baseline FFQ1 except for fat. The percentage of increase varies between 1.5% and 96%. Results of the second FFQ indicated an overestimation of intake for most nutrients (macro and micro). Macronutrient intakes assessed by the two FFQ and 24 hDR were strongly correlated. The correlation coefficients for micronutrient intakes between FFQ2 and 24hDR were lower than that of the two FFQs except for calcium (r = 0.55) and sodium (r = 0.643). They ranged from (-0.17) for fluorine to (0.643) for sodium. The agreement rates for classifying macronutrient intakes into same or adjacent quartile were between 79.4% and 100% for the two FFQs and between 71% and 100% for the second FFQ and 24hDR. The reported consumption of food groups estimated by FFQ2 was significantly higher than that reported by FFQ1. In conclusion, the developed FFQ was sufficiently valid to assess energy and macronutrients but not micronutrients. The reliability was adequate for most nutrients.


Assuntos
Inquéritos sobre Dietas , Ingestão de Alimentos/fisiologia , Comportamento Alimentar , Nutrientes/análise , Adulto , Estudos de Coortes , Dieta , Humanos , Catar , Reprodutibilidade dos Testes
7.
Vet World ; 14(1): 120-128, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33642795

RESUMO

BACKGROUND AND AIM: Interest in plants with antimicrobial properties has been revived due to emerging problems associated with using antibiotics to eradicate Helicobacter pylori. Accordingly, this study aims to assess the antibacterial effects of Punica granatum and the possible synergistic effect of its extract along with metronidazole against H. pylori. MATERIALS AND METHODS: Pomegranate peel ethanol extracts (PPEE) was tested against a control strain of H. pylori (NCTC 11916) in vitro and in vivo in female Wistar rats. Moreover, the synergistic effect of PPEE in combination with metronidazole was tested in vitro. RESULTS: The PPEE exhibited a remarkable activity against H. pylori with a minimum inhibitory concentration (MIC) of 0.156 mg/mL. Furthermore, the extract exhibited a pronounced urease inhibitory activity (IC50 ~6 mg/mL) against the tested strain. A synergistic effect between PPEE and metronidazole was also observed (fractional inhibitory concentrations <0.5). Oral treatment of rats with PPEE for 8 days produced a significant reduction in H. pylori gastritis and a significant decrease in both lymphocytic and positive chronicity. CONCLUSION: Pomegranate extract is probably safe and represents a potential alternative and complementary therapy for reducing H. pylori associated with gastric ulcers.

8.
J Health Psychol ; 26(11): 1988-1998, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-31830806

RESUMO

We studied whether mood and demographics are related to body mass index in a population of Syrian and Iraqi refugees residing in Jordan. Questionnaires and Brunel Mood Scale were used to collect demographical data. Data were analyzed using t-test and analysis of variance. A high prevalence of overweight and obesity was observed in this population (60.5%). Mood subscales were not associated with body mass index categories. However, body mass index as a continuous variable was associated with anger, depression, and fatigue scores. Linear regression revealed that age, ethnicity, unemployment, chronic illnesses, and physical activity level, but not mood, are associated with body mass index.


Assuntos
Refugiados , Índice de Massa Corporal , Doença Crônica , Humanos , Jordânia/epidemiologia , Síria/epidemiologia
9.
J Exp Med ; 173(6): 1521-8, 1991 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-1851800

RESUMO

Lymphocyte chemoattractant factor (LCF) is a tetrameric glycoprotein of 56,000 relative molecular mass produced by activated T lymphocytes. LCF binds to CD4 and has previously been found to stimulate migration of CD4+ lymphocytes and monocytes. Because human eosinophils, like T cells and monocytes, express CD4, we examined functional responses of eosinophils to LCF. Recombinant LCF (rLCF) expressed in COS cells was purified on a CD4 affinity column. Migration of eosinophils was elicited by rLCF at low concentrations: the 50% effective dose (ED50) was 10(-12) to 10(-11) M, concentrations 100- to 1,000-fold lower than the ED50s for the recognized eosinophil chemoattractants C5a and platelet-activating factor. Two other ligands which bound to CD4, human immunodeficiency virus-1 envelope glycoprotein gp120 and monoclonal antibody OKT4, also stimulated eosinophil migration. Monovalent OKT4 Fab competitively inhibited eosinophil responses to rLCF. rLCF did not influence other functional responses of eosinophils tested, including degranulation, superoxide generation, leukotriene C4 production, in vitro survival, or surface expression of the adherence receptor CR3 (CD11b), human histocompatibility leukocyte antigen DR, or interleukin 2 receptor p55 (CD25). We conclude that CD4 on eosinophils is capable of transducing a migratory stimulus and serves as a receptor for a chemoattractant lymphokine LCF. T cell-derived LCF may contribute to recruitment of eosinophils and CD4+ mononuclear cells concomitantly at inflammatory reactions.


Assuntos
Antígenos CD4/fisiologia , Fatores Quimiotáticos/fisiologia , Quimiotaxia de Leucócito , Eosinófilos/fisiologia , Linfocinas/fisiologia , Eosinófilos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Antígenos HLA-DR/análise , Humanos , Técnicas In Vitro , Interleucina-16 , Neutrófilos/fisiologia , Receptores de Interleucina-2/análise , Superóxidos/metabolismo
10.
J Exp Med ; 172(3): 673-81, 1990 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-1696954

RESUMO

Transforming growth factor alpha (TGF-alpha) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-alpha (hTGF-alpha). No other identifiable leukocytes in these lesions contained detectable hTGF-alpha mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient's neutrophils or mononuclear cells, were positive for hTGF-alpha mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-alpha peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-alpha was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-alpha mRNA and none of these eosinophils contained immunohistochemically detectable TGF-alpha product. Taken together, these findings establish that human eosinophils can express TGF-alpha, but suggest that the expression of TGF-alpha by eosinophils may be under microenvironmental regulation. Demonstration of TGF-alpha production by tissue-infiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses.


Assuntos
Adenocarcinoma/genética , Neoplasias do Colo/genética , Eosinófilos/metabolismo , Neoplasias Bucais/genética , Fatores de Crescimento Transformadores/genética , Sequência de Bases , Northern Blotting , Linhagem Celular , Eosinofilia/sangue , Eosinofilia/genética , Humanos , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , RNA/genética , RNA/isolamento & purificação , RNA Mensageiro/genética , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Síndrome , Fatores de Crescimento Transformadores/sangue
11.
Appl Physiol Nutr Metab ; 45(3): 340-343, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31751150

RESUMO

This study compared the weight loss efficacy of alternate-day fasting (ADF) versus daily calorie restriction (CR) in adults with subclinical hypothyroidism. After 6 months, body weight decreased (P < 0.001) similarly by ADF (-7% ± 1%) and CR (-8% ± 2%). Insulin resistance decreased (P < 0.05) more by ADF versus CR. Free thyroxin and thyroid-stimulating hormone remained unchanged. Thus, ADF and CR produce similar weight loss in this population, without affecting thyroid hormone levels. Novelty Intermittent fasting and daily restriction produce similar reductions in body weight in subjects with subclinical hypothyroidism.


Assuntos
Restrição Calórica/métodos , Jejum/fisiologia , Hipotireoidismo/complicações , Obesidade/complicações , Obesidade/dietoterapia , Redução de Peso/fisiologia , Adolescente , Adulto , Idoso , Dieta Redutora/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
J Clin Invest ; 88(3): 825-32, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1885772

RESUMO

Because T cell-derived cytokines may affect the functioning of eosinophils, we have investigated the capacity of human eosinophils to respond to IL-2. IL-2 was a potent chemoattractant with ED50 of 10(-12) M with eosinophils from all normal and eosinophilic donors tested. The monoclonal antibodies anti-Tac and TU27 against p55 (Tac/CD25) and p75 receptor subunits, respectively, each inhibited IL-2-dependent eosinophil migration. The molar potency of IL-2 and the inhibitory activity of each of the above antibodies suggest that high affinity heterodimeric IL-2 receptor complexes mediated the migration responses of eosinophils to IL-2. Binding of monoclonal antibody against p75 was not detectable by flow cytometry, and high affinity binding sites for 125I-IL-2 were below the limits of quantitation on eosinophils from individuals with eosinophilia. Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA. Surface expression of p55 on eosinophils from normal or eosinophilic individuals increased during culture for 24-48 h with a biologic activity purified from stimulated U937 cells and to a lesser extent with granulocyte-macrophage CSF or lymphocyte chemoattractant factor but not with nine other cytokines. These studies indicate that blood eosinophils respond to IL-2 and identify one mechanism whereby activation of T lymphocytes may influence the function of eosinophils.


Assuntos
Eosinófilos/química , Receptores de Interleucina-2/análise , Movimento Celular/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-2/metabolismo , Interleucina-2/farmacologia , Interleucina-5/farmacologia , RNA Mensageiro/análise
13.
Pediatr Pulmonol ; 42(7): 592-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17534970

RESUMO

Stachybotrys chartarum (atra) is a toxic mold that grows on water-damaged cellulose-based materials. Research has revealed also that inhalation of S. chartarum spores caused marked changes in respiratory epithelium, especially to developing lungs. We analyzed the epigenetic potential of S. chartarum spore toxins on developing rat lung fibroblasts using single cell gel electrophoresis (comet assay). Isolated fetal lung fibroblasts were exposed to S. chartarum spore toxins for 15 min, 3, 14, or 24 hr and control cells were exposed to saline under the same conditions. Cells were embedded in agarose, electrophoresed under alkaline conditions and silver stained. DNA damage was assessed in terms of fragmentation as measured by comet tail length (DNA migration) and intensity (% DNA contained within head and tail). Upon visual inspection, control fibroblasts showed no DNA fragmentation whereas S. chartarum-treated cells had definable comets of various degrees depending upon the time-course. Analyses of the comets revealed that exposure to S. chartarum spore toxins for at least 15 min to 14 hr, induced increased DNA fragmentation in a time-dependent manner. The fact that exposure to toxins for 24 hr showed less damage suggested that developing lung fibroblasts may have the capability of repairing DNA fragmentation.


Assuntos
Fragmentação do DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Pulmão/citologia , Pulmão/embriologia , Micotoxinas/farmacologia , Stachybotrys , Animais , Ratos , Ratos Sprague-Dawley
14.
Biochim Biophys Acta ; 750(1): 78-90, 1983 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-6402030

RESUMO

The presence of arachidonic acid lipoxygenase pathways in murine eosinophils was demonstrated by the isolation and identification of several lipoxygenase products from incubations of these cells. The most abundant arachidonate metabolite from murine eosinophils stimulated with ionophore A23187 and exogenous arachidonic acid was 12-S-hydroxyeicosatetraenoic acid (12-S-HETE), and the next most abundant was 15-HETE. Two families of leukotrienes were also recovered from these incubations. One family comprised the hydrolysis products of leukotriene A4, and the other included products derived from the 14,15-oxido analog of leukotriene A4 (14,15-leukotriene A4). Two double oxygenation products of arachidonate were also identified. These compounds were a 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) and a 5,12-dihydroxyeicosatetraenoic acid (5,12-diHETE). Eosinophil stimulation promoter is a murine lymphokine which enhances the migration of eosinophils. When murine eosinophils were incubated with eosinophil stimulation promoter in concentrations sufficient to produce a migration response, a 2-3-fold increase in the production of 12-HETE was observed compared to unstimulated cells. Coupled with the recent demonstration that arachidonic acid lipoxygenase inhibitors suppress the migration response to eosinophil stimulation promoter and that 12-HETE induces a migration response, this observation provides further evidence in support of the hypothesis that eosinophil stimulation promoter stimulation of eosinophils results in the generation of lipoxygenase products which modulate the migratory activity of the cells.


Assuntos
Ácidos Araquidônicos/sangue , Eosinófilos/metabolismo , Lipoxigenase/sangue , Animais , Araquidonato Lipoxigenases , Ácido Araquidônico , Dinoprosta , Cinética , Espectrometria de Massas , Camundongos , Prostaglandinas F/sangue
15.
Toxicol Sci ; 84(1): 186-94, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15574675

RESUMO

Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabeled with 3H-choline and incubated with spore extract showed decreased incorporation of 3H-choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.


Assuntos
Colina-Fosfato Citidililtransferase/metabolismo , Feto/metabolismo , Fosfolipídeos/metabolismo , Stachybotrys/fisiologia , Tensoativos/farmacologia , Animais , Separação Celular , Células Cultivadas , Colina/metabolismo , Cromatografia Líquida de Alta Pressão , Citidina Difosfato Colina/metabolismo , Citosol/metabolismo , Feminino , Feto/citologia , Fosfatidilcolinas/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Esporos Fúngicos/química
16.
J Toxicol Environ Health A ; 68(15): 1321-35, 2005 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-16020192

RESUMO

Stachybotrys chartarum is an important toxigenic fungus that has been associated with respiratory disease onset in animals and humans. It can be separated into macrocyclic trichothecene-producing and nonproducing chemotypes based on secondary metabolite production. However, effects of spores of the two chemotypes on lung inflammatory responses are poorly understood. In this study, real-time reverse-transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA) were used to investigate time-course (1, 3, 6, 24, and 48 h post-instillation [PI]) relationships in mice intratracheally exposed to 300 spores/g body weight of a macrocyclic trichothecene-producing (JS 58-17) and a nonproducing (JS 58-06) S. chartarum isolate and of Cladosporium cladosporioides. There were marked differences in the magnitude and temporal patterns of mouse lung immune responses to intratracheal exposure to spores of these species at this spore dose. Both macrophage inflammatory protein 2 (MIP-2) and surfactant protein-D (SP-D) mRNA expression were significantly upregulated in lungs of JS 58-17-treated animals compared to that of all other treatment animals at 6 and 24 h PI. Heightened mRNA expression of these immunomodulators combined with comparatively depressed MIP-2 and tumor necrosis factor (TNF)-a protein expression suggests that the action of macrocyclic trichothecenes sequestered in 58-17 spores is involved. Interestingly, TNF-a protein expression in all spore treatment animal groups was also significantly increased over that in saline controls. Similarities in expression among all spore treatment animals suggest that chemicals other than toxic secondary metabolites, and possibly spore-sequestered 1,3-beta-D-glucan, may contribute to lung pathogenesis.


Assuntos
Fatores Imunológicos/imunologia , Pneumopatias Fúngicas/imunologia , RNA Mensageiro/isolamento & purificação , Stachybotrys/patogenicidade , Animais , Quimiocina CXCL2 , Quimiocinas/genética , Quimiocinas/imunologia , Fatores Imunológicos/genética , Masculino , Camundongos , RNA Mensageiro/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Stachybotrys/isolamento & purificação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
17.
Exp Hematol ; 18(8): 897-902, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2201555

RESUMO

Human recombinant (r) and chemically synthesized granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to enhance the attachment of neutrophils to monolayers of human umbilical vein endothelial cells by direct action upon the neutrophil. Using synthetic peptides of GM-CSF with truncated amino and carboxy termini, a region between amino acids 14 and 24 was found to be essential for neutrophil attachment. In analysis of the response of neutrophils from individual donors, a heterogeneity in their capacity to respond to GM-CSF by increased adherence was observed. The level of response to GM-CSF did not depend on receptor number. However, a positive correlation (r = 0.58) was found between the ability to respond to GM-CSF and the level of response to tumor necrosis factor--suggesting a link between the responses of neutrophils to these two cytokines. The stimulation of neutrophil adhesiveness to endothelial cells by rGM-CSF and the heterogeneity in donor response may have important implications for the clinical administration of GM-CSF.


Assuntos
Adesão Celular , Fatores Estimuladores de Colônias/farmacologia , Endotélio Vascular/citologia , Substâncias de Crescimento/farmacologia , Neutrófilos/fisiologia , Adulto , Ligação Competitiva , Células Cultivadas , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/farmacologia , Proteínas Recombinantes/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais
18.
Pediatrics ; 81(1): 63-5, 1988 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3275934

RESUMO

Among 78 cases of group B streptococcal infections in children hospitalized at our institution during 1981 to 1985, five cases of cellulitis in infants were identified. Age at onset was 4 to 11 weeks. Group B streptococci were isolated from each of two aspirate cultures, all four blood cultures obtained before administering antibiotics, and none of four spinal fluid cultures obtained. All five infants had previously been treated with IV antibiotics in the hospital. Two infants had been previously treated for group B streptococcal infections (one each meningitis and neonatal sepsis). In contrast, among the 29 other patients with late-onset (2 weeks of age or older) group B streptococcal infection, four had prior treatment with IV antibiotics (P less than .001). These data suggest that hospitalization and/or parenteral antibiotic therapy may be a risk factor for development of group B streptococcal cellulitis.


Assuntos
Antibacterianos/uso terapêutico , Celulite (Flegmão)/etiologia , Hospitalização , Infecções Estreptocócicas/etiologia , Ampicilina/uso terapêutico , Antibacterianos/administração & dosagem , Celulite (Flegmão)/complicações , Celulite (Flegmão)/patologia , Feminino , Gentamicinas/uso terapêutico , Humanos , Lactente , Infusões Intravenosas , Masculino , Fatores de Risco , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/patologia , Streptococcus agalactiae
19.
Mol Vis ; 5: 40, 1999 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-10617777

RESUMO

PURPOSE: These investigations were undertaken to compare and contrast the roles of phosducin and phosducin-like protein in the retina. METHODS: Phosducin and phosducin-like protein were compared in an in vitro assay measuring their inhibition of transducin binding to light-activated rhodopsin. The two proteins were localized within the retina by immunoblot analyses and immunocytochemistry using affinity-purified antibodies with high specificity for each of the two homologs. The sensitivity of phosducin-like protein to phosphorylation was probed using in vitro protein kinase reactions. RESULTS: Phosducin and phosducin-like protein were found to have similar, though not identical, transducin inhibiting activity in vitro. These two proteins were found to be localized dissimilarly within the retina, with spatial overlap limited to the inner segments of the photoreceptors. Phosducin is found exclusively in photoreceptor cells, including the synaptic and nuclear layers, while phosducin-like protein is found throughout the inner retinal layers, most abundantly in the bipolar cells of the inner nuclear layer. Phosducin-like protein is not efficiently phosphorylated by the protein kinases tested, indicating that its regulation differs from that of phosducin. CONCLUSIONS: It appears that phosducin and phosducin-like protein play distinct roles in the retina. While phosducin is likely to be important in feedback regulation of the visual signal, such as in light adaptation, phosducin-like protein probably has little if any function in the phototransduction cascade. Phosducin-like protein may have a role in regulating the processing of visual signals by the neural cells of the inner retina.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Transporte/fisiologia , Proteínas do Olho/metabolismo , Proteínas do Olho/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Fosfoproteínas/metabolismo , Fosfoproteínas/fisiologia , Retina/metabolismo , Animais , Especificidade de Anticorpos , Proteínas de Transporte/imunologia , Proteínas de Transporte/farmacologia , Bovinos , Proteínas do Olho/imunologia , Reguladores de Proteínas de Ligação ao GTP , Proteínas de Ligação ao GTP/metabolismo , Immunoblotting , Imuno-Histoquímica , Camundongos , Chaperonas Moleculares , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/farmacologia , Fosfoproteínas/imunologia , Fosforilação , Ligação Proteica/efeitos dos fármacos , Proteína Quinase C/metabolismo , Retina/enzimologia , Rodopsina/metabolismo , Segmento Externo da Célula Bastonete/metabolismo
20.
Invest Radiol ; 33(8): 433-8, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9704281

RESUMO

RATIONALE AND OBJECTIVES: The authors evaluate the role of low-field strength magnetic resonance imaging (MRI) compared with sonography in the evaluation of degenerative changes of tendons, with histologic correlation, based on investigations of horse cadavers. METHODS: Low-field MRI and sonography was performed in 42 hours specimens for the evaluation of tendons and ligaments. Magnetic resonance imaging included sagittal and axial T1-weighted, T2-weighted, and gradient echo images. Sonography and MR images were evaluated for degenerative changes or tears and the findings were correlated with the histologic results. RESULTS: Using histologic findings as a gold standard, the accuracy for the sonographic evaluation was 65.9%, sensitivity was 16.7%, and specificity was 100%. The corresponding data for low-field MR imaging were 70.5% accuracy, 44.4% sensitivity, and 88.5% specificity. CONCLUSIONS: Low-field MRI investigation allows more accurate staging of tendinous changes than sonography. It is more reproducible and potentially includes the advantages of the combined evaluation of bones, ligaments, and soft tissue.


Assuntos
Imageamento por Ressonância Magnética , Tendões/diagnóstico por imagem , Tendões/patologia , Animais , Cavalos , Técnicas In Vitro , Ligamentos/diagnóstico por imagem , Ligamentos/patologia , Doenças Musculares/diagnóstico , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/patologia , Sensibilidade e Especificidade , Ultrassonografia
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