RESUMEN
The relatively low long-term survival rate of lung transplant recipients as compared to other organ recipients serves as an impetus to identify potential lung dysfunction as early as possible. There is an association between donor heavy alcohol use and acute lung injury in the lung allograft after transplant, known as primary graft dysfunction. Excessive alcohol use (EAU) can induce pulmonary immune dysregulation in response to an infection. Antimicrobial peptides (AMPs) are an important component of the innate immune response to pulmonary infections, but the impact of EAU on AMPs in the allograft lung has not been evaluated. Our hypothesis is that specific lung AMPs, LL-37, α-defensin-1,2,3, and ß-defensin-2, are dysregulated in the lungs from organ donors who had EAU. In this prospective observational investigation, we measured AMPs via ELISA and inflammatory cytokines via multiplex bead array, in bronchoalveolar lavage (BAL) fluid of lung allograft donors, comparing results based on their alcohol consumption. LL-37 levels in lung donors with EAU were found to be increased compared to nondrinker (ND) donors [median 7.7 ng/mL (IQR 4.1-37.0) vs. 2.3 ng/mL (IQR 1.1-7.9), p = 0.004], whereas α-defensins-1,2,3 were decreased only in the presence of an infection in donors with EAU compared to ND donors [median 2.2 ng/mL (IQR 1.6-2.4) vs. 3.2 ng/mL (IQR 2.3-3.8), p = 0.049]. There was no difference in ß-defensin-2 levels. Gene expression levels of these AMPs were not different. Elevated levels of CXCL8 were noted in bronchial washings of donors with EAU compared to ND donors, [median 4372 pg/mL (IQR 3352-13180) vs. 867.3 pg/mL (IQR 163.6-3675), p = 0.04], suggesting a potentially heightened inflammatory response. At 1 month post-transplant, LL-37 and CXCL8 levels are decreased compared to levels at time of transplant. In lung donors with EAU, LL-37 and α-defensins-1,2,3 dysregulated levels in the presence of an infection may be a harbinger of dysfunction of the lungs through the transplant process.
Asunto(s)
Alcoholismo/complicaciones , Péptidos Catiónicos Antimicrobianos/análisis , Pulmón/efectos de los fármacos , Adulto , Líquido del Lavado Bronquioalveolar/química , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Pulmón/química , Pulmón/metabolismo , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Adulto Joven , CatelicidinasRESUMEN
Several studies suggest that light in the UVA range (320-400 nm) activates signaling pathways that are anti-inflammatory and antioxidative. These effects have been attributed to Nrf2-mediated upregulation of "phase 2" genes such as heme oxygenase-1 (HO-1) that neutralize oxidative stress and metabolize electrophiles. Proteomics analysis previously had shown that small doses of blue light (400-500 nm) increased levels of peroxiredoxin phase 2 proteins in THP-1 monocytes, which led to our hypothesis that blue light activates Nrf2 signaling and thus may serve as an anti-inflammatory agent. THP-1 monocytes were treated with doses of blue light with and without lipopolysaccharide (LPS) inflammatory challenge. Cell lysates were tested for Nrf2 activation and HO-1 production. Treated cells were assessed for viability/mitochondrial activity via trypan blue exclusion and MTT assay, and secretion of two major pro-inflammatory cytokines, interleukin 8 (IL8) and tumor necrosis factor alpha (TNFα) was measured using ELISA. Blue light activated the phase 2 response in cultured THP-1 cells and was protective against LPS-induced cytotoxicity. Light pre-treatment also significantly reduced cytokine secretion in response to 0.1 µg ml-1 LPS, but had no anti-inflammatory effect at high LPS levels. This study is the first to report these effects using a light source that is approved for routine use on dental patients. Cellular responses to these light energies are worth further study and may provide therapeutic interventions for inflammation.
Asunto(s)
Inflamación/metabolismo , Luz , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de la radiación , Células Cultivadas , Humanos , Células THP-1RESUMEN
STUDY OBJECTIVE: To determine whether prenatal depressive symptoms are associated with postpartum sexual risk among young, urban women of color. DESIGN: Participants completed surveys during their second trimester of pregnancy and at 1 year postpartum. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression Scale, excluding somatic items because women were pregnant. Logistic and linear regression models adjusted for known predictors of sexual risk and baseline outcome variables were used to assess whether prenatal depressive symptoms make an independent contribution to sexual risk over time. SETTING: Fourteen community health centers and hospitals in New York City. PARTICIPANTS: The participants included 757 predominantly black and Latina (91%, n = 692) pregnant teens and young women aged 14-21 years. INTERVENTIONS AND MAIN OUTCOME MEASURES: The main outcome measures were number of sex partners, condom use, exposure to high-risk sex partners, diagnosis of a sexually transmitted disease, and repeat pregnancy. RESULTS: High levels of prenatal depressive symptoms were significantly associated with increased number of sex partners (ß = 0.17; standard error, 0.08), decreased condom use (ß = -7.16; standard error, 3.08), and greater likelihood of having had sex with a high-risk partner (odds ratio = 1.84; 95% confidence interval, 1.26-2.70), and repeat pregnancy (odds ratio = 1.72; 95% confidence interval, 1.09-2.72), among participants who were sexually active (all P < .05). Prenatal depressive symptoms were not associated with whether participants engaged in postpartum sexual activity or sexually transmitted disease incidence. CONCLUSION: Screening and treatment for depression should be available routinely to women at risk for antenatal depression.
Asunto(s)
Negro o Afroamericano/psicología , Depresión Posparto/psicología , Depresión/diagnóstico , Hispánicos o Latinos/psicología , Complicaciones del Embarazo/psicología , Conducta Sexual/psicología , Adolescente , Conducta Anticonceptiva/psicología , Conducta Anticonceptiva/estadística & datos numéricos , Depresión/psicología , Femenino , Humanos , Incidencia , Modelos Logísticos , Ciudad de Nueva York/epidemiología , Oportunidad Relativa , Periodo Posparto , Embarazo , Complicaciones del Embarazo/diagnóstico , Segundo Trimestre del Embarazo/psicología , Medición de Riesgo/métodos , Factores de Riesgo , Parejas Sexuales , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/etiología , Encuestas y Cuestionarios , Sexo Inseguro/psicología , Sexo Inseguro/estadística & datos numéricos , Adulto JovenRESUMEN
Fifty-four individually-fed Hereford-Angus cross steers (initial BW = 308 ± 9 kg) were used in an unbalanced randomized block design with a 2 × 2 factorial treatment arrangement to determine effects of corn processing method and corn wet distillers grains plus solubles (WDGS) inclusion in finishing diets on animal performance, carcass and beef characteristics, and sensory attributes. Dietary treatments included steam-flaked corn- (SFC) and dry-rolled corn (DRC)-based finishing diets containing 0 or 35% WDGS (DM basis; 0SFC and 35SFC, 0DRC and 35DRC, respectively). Yellow grease was used to equilibrate fat content of diets. Steers were fed 174 d, and were harvested on a single date when the mean ultrasound fat thickness was estimated to be 1.30 cm. No interactions between corn processing and WDGS were observed for performance or carcass characteristics (P ≥ 0.11). Final BW (556 ± 14 kg) and ADG (1.43 ± 0.06 kg) were not affected (P ≥ 0.25) by dietary treatment. Steers fed SFC-based diets consumed less feed, and were 10.6% more efficient (P < 0.01) than those fed DRC-based diets. Including WDGS in finishing diets improved feed efficiency of steers consuming both SFC- and DRC-based diets (P ≤ 0.04). Dietary treatment did not affect HCW, dressing percentage, fat thickness, or yield grade (P ≥ 0.27). Including WDGS in finishing diets decreased the concentration of 16:1cis-9, 18:1cis-9, and 18:1cis-11 fatty acids, and tended (P ≤ 0.10) to increase total fat concentration of steaks compared with diets without WDGS. A corn processing method by WDGS interaction was detected for 18:1trans-11 where steaks from 0DRC diets had decreased concentrations compared with other diets. There were no dietary effects on palatability attributes (P > 0.20). Livery-organy aromatics (P = 0.03) and sweet basic tastes (P = 0.01) in steaks from the 35SFC treatment were more intense than in other treatments, but were barely detectable. Thiobarbituric acid reactive substances tended to be greater in steaks from steers fed WDGS after 5 d of storage (P = 0.10), and were greater after 7 d. (P < 0.01). Inclusion of WDGS used in this experiment improved G:F with minimal impacts on carcass characteristics. Both WDGS inclusion and corn processing method impacted fatty acid composition. However, diet had minimal impacts on palatability attributes. When compared with diets fat-equilibrated with yellow grease, the primary concern with incorporating WDGS appears to be decreased shelf-life after 5 d of storage.
Asunto(s)
Bovinos/fisiología , Dieta/veterinaria , Ácidos Grasos/análisis , Carne/análisis , Zea mays , Animales , Bovinos/crecimiento & desarrollo , Digestión/fisiología , Ingestión de Alimentos/fisiología , Calidad de los Alimentos , Masculino , Carne/normasRESUMEN
Internal carotid artery dissection (ICAD) is an important cause of acute ischemic stroke in younger patients. Potential acute treatments include anticoagulation, intravenous thrombolysis (IVT), and endovascular thrombectomy (ET). We report a case where the use of IVT followed by ET resulted in a good clinical outcome in a patient with tandem internal carotid and middle cerebral artery occlusion following ICAD.
RESUMEN
Blue light curing units (wavelengths of 400-500 nm) are a mainstay of restorative dentistry, and several high-intensity light sources have been developed to polymerize resin composites more rapidly. The biological safety of visible light has been assumed, but some reports of adverse biological effects of blue light in non-dental contexts support further evaluation of the biological safety of high-intensity blue light. The current study tested the hypothesis that blue light provokes cell stress responses resulting in the secretion of cytokines or expression of heat-shock proteins (HSP) in monocytes. Human monocytic cells were irradiated with three light sources (quartz-tungsten-halogen, plasma-arc and laser), then cellular proliferation, secretion of the inflammatory cytokine TNFalpha and induction of HSP72 were measured. Results indicated that although all three light sources significantly inhibited proliferation of monocytes, the secretion of TNFalpha was not induced following exposure to blue light and was not potentiated with administration of the activator lipopolysaccharide. Similarly, treatment with the plasma-arc light, which caused the largest temperature increase in previous studies, did not induce HSP72. The current results do not support activation of monocytes by blue light as an inflammatory risk factor in dental tissues during curing of composites. However, the results of the current study should be further verified in primary monocytes and an animal model before decisions about clinical risks are made.
Asunto(s)
Resinas Compuestas , Recubrimiento Dental Adhesivo/métodos , Luz/efectos adversos , Monocitos/efectos de la radiación , Proliferación Celular/efectos de la radiación , Células Cultivadas , Proteínas del Choque Térmico HSP72/metabolismo , Halógenos , Humanos , Rayos Láser/efectos adversos , Monocitos/inmunología , Monocitos/metabolismo , Cuarzo , Tecnología Odontológica , Temperatura , Factor de Necrosis Tumoral alfa/metabolismo , TungstenoRESUMEN
AIM: To test the hypothesis that extending the time of a traditional ex vivo cytotoxicity test helps to identify trends in the behaviour of root core materials and sealers, which could ultimately aid in predicting their clinical safety and performance. METHODOLOGY: Endodontic sealers and core specimens were initially tested in direct contact with L929 fibroblasts for 72 h. Cell response was estimated by measuring cellular succinate dehydrogenase activity relative to Teflon controls. Cytotoxicity (% of more active cells) was reassessed after 1, 3, 4 and 6 weeks, with the specimens stored in a physiologically balanced salt-solution between tests. RESULTS: Distinct trends in cytotoxicity among both core materials and sealers were observed over the 6-week test. Four of the six sealers and two of the three core materials showed cell viabilities of <30% of Teflon after 6 weeks (>70% cytotoxicity). CONCLUSIONS: The current results suggest that some endodontic materials have an elevated biological risk for extended intervals.
Asunto(s)
Materiales de Obturación del Conducto Radicular/toxicidad , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colorantes , Resinas Compuestas/toxicidad , Dimetilpolisiloxanos/toxicidad , Combinación de Medicamentos , Resinas Epoxi/toxicidad , Fibroblastos/efectos de los fármacos , Predicción , Gutapercha/toxicidad , Ensayo de Materiales , Ratones , Mitocondrias/enzimología , Poliésteres/toxicidad , Cementos de Resina/toxicidad , Seguridad , Succinato Deshidrogenasa/efectos de los fármacos , Sales de Tetrazolio , Tiazoles , Factores de Tiempo , Cemento de Óxido de Zinc-Eugenol/toxicidadRESUMEN
UNLABELLED: Monosodium titanate (MST) particles effectively bind specific metals and are therefore promising compounds for delivery or sequestration of metals in biological contexts. Yet, the biological properties of MST are largely unexplored. Our previous study showed that the cytotoxicity of these compounds was mild, but the nature of the dose response curves suggested that residual titanates in culture may have interfered with the assay. In the current study, we assessed the importance of these artifacts, and extended our previous results using fibroblasts for biological evaluation. We also assessed the biological response to a new type of titanate (referred to as amorphous peroxo-titanate or APT) that shows more promising metal binding properties than MST. METHODS: The degree of titanate-induced interference in the MTT (mitochondrial activity assay) was estimated by means of cell-free assays with and without a final centrifugation step to remove residual titanate particulate. Cytotoxic responses to titanates were assessed by measuring succinate dehydrogenase activity (by MTT) in THP1 monocytes or L929 fibroblasts after 24-72 h exposures. Monocytic activation by APT was assessed by TNFalpha secretion (ELISA) from monocytes with or without lipopolysaccharide (LPS) activation. RESULTS: We confirmed that residual titanate particulates may alter the SDH activity assay, but that this effect is eliminated by adding a final centrifugation step to the standard MTT procedure. Addition of MST or APT at concentrations up to 100 mg/L altered succinate dehydrogenase activity by < 25% in both monocytes and fibroblasts. Fibroblasts displayed time-dependent adaptation to the MST. APT did not trigger TNFalpha secretion or modulate LPS-induced TNFalpha secretion from monocytes. CONCLUSIONS: Although further in vitro and in vivo assessment is needed, MST and APT exhibit biological properties that are promising for their use as agents to sequester or deliver metals in biological systems.
Asunto(s)
Materiales Biocompatibles/toxicidad , Fibroblastos/efectos de los fármacos , Monocitos/efectos de los fármacos , Óxidos/toxicidad , Titanio/toxicidad , Animales , Materiales Biocompatibles/química , Línea Celular , Fibroblastos/enzimología , Humanos , Ensayo de Materiales , Ratones , Mitocondrias/efectos de los fármacos , Monocitos/inmunología , Óxidos/química , Succinato Deshidrogenasa/análisis , Titanio/química , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Resin composites are widely used in dentistry, and are polymerized in situ using a blue-light activated, free-radical polymerization mechanism. Blue light (400-500nm) is used to activate camphoroquinone (CQ), which decomposes to form free radicals that are stabilized by dimethyl-p-toludine (DMPT). CQ and DMPT are applied near tooth pulpal tissues and are irradiated during restorative procedures, suggesting that pulpal cells are exposed to free radicals. Because glutathione is a major component of the cellular redox management system, we tested the hypothesis that blue light irradiation would shift cellular glutathione redox balance of cells exposed to CQ and DMPT. We also measured NFkappaB activation, a redox-sensitive transcription factor that regulates inflammatory responses and glutathione synthetic enzyme levels. THP1 human monocytes were exposed to sublethal levels of CQ (0.4 mM) or DMPT (1.0 mM), with or without blue light exposure (25 J/cm(2)) from a quartz-tungsten-halogen source. The ratio of reduced to oxidized glutathione was measured using as assay based on 5,5'-dithio-bis(2-nitrobenszoic acid). NFkappaB transactivation was measured by transfection of an NFkappaB-containing plasmid linked to a luciferase reporter. Our results showed that blue light, CQ, or DMPT alone had no significant effect on cellular glutathione redox balance, but that the combination of these agents induced a marked oxidative bias, and reduced total glutathione levels up to 50%. On the other hand, light, CQ, and DMPT alone or in combination suppressed NFkappaB transactivation by >70%. Our results suggest that CQ and DMPT pose risks to pulpal tissues with or without blue light irradiation, and that multiple, interacting mechanisms shape the response to these agents.
Asunto(s)
Radicales Libres/metabolismo , Luz , Monocitos/efectos de los fármacos , Monocitos/efectos de la radiación , Terpenos/farmacología , Toluidinas/farmacología , Línea Celular , Glutatión/metabolismo , Humanos , Monocitos/enzimología , Monocitos/metabolismo , FN-kappa B/genética , Oxidación-Reducción/efectos de los fármacos , Oxidación-Reducción/efectos de la radiación , Succinato Deshidrogenasa/metabolismo , Activación Transcripcional/efectos de los fármacos , Activación Transcripcional/genéticaRESUMEN
Biomedical implants significantly improve the quality of life in an ever-increasing number of patients. However, inflammation of tissues around implants remains a long-term, post-placement sequelae that may contribute to implant failure. Infection-mediated failure is partly a consequence of inappropriate host response and chronic inflammation, and is mediated primarily by the secretory products of monocytes and macrophages. Although the secretion of inflammatory mediators from activated monocytes is well characterized, the resolution of mediator levels post-activation is relatively unstudied. The current study defines the time course of cytokine secretion by activated human monocytes after the activator has been removed. THP1 human monocytes were activated by LPS, and cytokine secretion was monitored over time after LPS removal using enzyme-linked immunosorbent assays (TNFalpha or IL8) or a cytokine array. The release of cytokines was compared with conditions without LPS removal. As expected, secretion of nearly all cytokines was reduced when LPS was removed, but the amount of the reduction was highly cytokine-dependent. Furthermore, levels of cytokines were stable in medium alone but not in cell-culture, suggesting an active process to either degrade or internalize secreted cytokines. Our results are consistent with clinical experience that inflammation resolves rapidly after treatment to remove bacteria or inflamed tissue. However, the differential cytokine regulation indicates a sophisticated coordination of cytokine levels probably associated with management of the wound healing response after removal of the bacterial insult. This wound healing response is one critical component of the long-term success of biomedical implants.
Asunto(s)
Citocinas/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Prótesis e Implantes/efectos adversos , Células Cultivadas , Citocinas/inmunología , Humanos , Inflamación/inmunología , Interleucina-8/inmunología , Lipopolisacáridos/inmunología , Monocitos/citología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
UNLABELLED: The biological response to dental restorative polymer composites is mediated by the release of unpolymerized residual monomers. Several new composite formulations claim to reduce unpolymerized residual mass. The current study assessed the cytotoxic responses to several of these new formations and compared them with more traditional formulations. Our hypothesis predicted that if these new polymerization chemistries reduce unpolymerized residual mass, the cytotoxicity of these materials also should be reduced relative to traditional formulations. METHODS: Materials (HerculiteXRV, Premise, Filtek Supreme, CeramxDuo, Hermes, and Quixfil) were tested in vitro in direct contact with Balb mouse fibroblasts, initially, then after aging in artificial saliva for 0, 1, 3, 5, or 8 weeks. The toxicity was determined by using the MTT assay to the estimate SDH activity. Knoop hardness of the materials also was measured at 0 and 8 weeks to determine whether surface breakdown of the materials in artificial saliva contributed to cytotoxic responses. RESULTS: Materials with traditional methacrylate chemistries (Herculite, Premise, Filtek Supreme) were severely (>50%) cytotoxic throughout the 8-week interval, but materials with newer chemistries or filling strategies (Hermes, CeramXDuo, and Quixfil) improved over time of aging in artificial saliva. Hermes showed the least cytotoxicity at 8 weeks, and was statistically equivalent to Teflon negative controls. Hardness of the materials was unaffected by exposure to artificial saliva. CONCLUSIONS: Newer polymerization and filling strategies for dental composites show promise for reducing the release of unpolymerized components and cytotoxicity.
Asunto(s)
Resinas Compuestas/química , Resinas Compuestas/toxicidad , Animales , Células 3T3 BALB , Técnicas In Vitro , Ensayo de Materiales , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Cementos de Resina/química , Cementos de Resina/toxicidad , SalivaRESUMEN
We described the characteristics in a referred cohort of type II diabetic patients in the Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes study evaluating the global prevalence and determinants of microalbuminuria (MA). A cross-sectional study evaluating 32,208 type II diabetic patients without known albuminuria from 33 countries was performed. Overall, 8057 patients were excluded, either because of prior known proteinuria or non-diabetic nephropathy (3670), or because of invalid urine collections (4387). One single random urinary albumin/creatinine ratio was obtained in 24,151 patients (75%). The overall global prevalence of normo-, micro-, and macroalbuminuria was 51, 39, and 10%, respectively. The Asian and Hispanic patients had the highest prevalence of a raised urinary albumin/creatinine ratio (55%) and Caucasians the lowest (40.6), P<0.0001. HbA1c, systolic blood pressure (BP), ethnicity, retinopathy, duration of diabetes, kidney function, body height, and smoking were all independent risk factors of MA, P<0.0001. Estimated glomerular filtration rate was below 60 ml/min/1.73 m(2) in 22% of the 11,573 patients with available data. Systolic BP below 130 mmHg was found in 33 and 43% had an HbA1c below 7%. The frequency of patients receiving aspirin was 32%, statins 29%, and BP-lowering therapy 63%. A high prevalence globally of MA and reduced kidney function, both conditions associated with enhanced renal and cardiovascular risk, was detected in type II diabetic patients without prior known nephropathy. Early detection, monitoring of vascular complications, and more aggressive multifactorial treatment aiming at renal and vascular protection are urgently needed.
Asunto(s)
Albuminuria/epidemiología , Albuminuria/etiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Derivación y Consulta , Factores de RiesgoRESUMEN
Blue light from dental photopolymerization devices has significant biological effects on cells. These effects may alter normal cell function of tissues exposed during placement of oral restorations, but recent data suggest that some light-induced effects may also be therapeutically useful, for example in the treatment of epithelial cancers. Reactive oxygen species (ROS) appear to mediate blue light effects in cells, but the sources of ROS (intra- versus extracellular) and their respective roles in the cellular response to blue light are not known. In the current study, we tested the hypothesis that intra- and extracellular sources of blue light-generated ROS synergize to depress mitochondrial function. Normal human epidermal keratinocytes (NHEK) and oral squamous cell carcinoma (OSC2) cells were exposed to blue light (380-500 nm; 5-60 J/cm(2)) from a dental photopolymerization source (quartz-tungsten-halogen, 550 mW/cm(2)). Light was applied in cell-culture media or balanced salt solutions with or without cells present. Intracellular ROS levels were estimated using the dihydrofluorescein diacetate (DFDA) assay; extracellular ROS levels were estimated using the leucocrystal violet assay. Cell response was estimated using the MTT mitochondrial activity assay. Blue light increased intracellular ROS equally in both NHEK and OSC2. Blue light also increased ROS levels in cell-free MEM or salt solutions, and riboflavin supplements increased ROS formation. Extracellularly applied ROS rapidly (50-400 muM, <1 min) increased intracellular ROS levels, which were higher and longer-lived in NHEK than OSC2. The type of cell-culture medium significantly affected the ability of blue light to suppress cellular mitochondrial activity; the greatest suppression was observed in DMEM-containing or NHEK media. Collectively, the data support our hypothesis that intra- and extracellularly generated ROS synergize to affect cellular mitochondrial suppression of tumor cells in response to blue light. However, the identity of blue light targets that mediate these changes remain unclear. These data support additional investigations into the risks of coincident exposure of tissues to blue light during material polymerization of restorative materials, and possible therapeutic benefits.
Asunto(s)
Queratinocitos/metabolismo , Luz , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Células Cultivadas , Humanos , Succinato DeshidrogenasaRESUMEN
Monosodium titanate (MST) is an inorganic sorbent/ion exchanger developed for the removal of radionuclides from nuclear wastes. We investigated the ability of MST to bind Cd(II), Hg(II), Au(III), or the Au-organic compound auranofin to establish the utility of MST for applications in environmental decontamination or medical therapy (drug delivery). Adsorption isotherms for MST were determined at pH 7-7.5 in water or phosphate-buffered saline. The extent of metal binding was determined spectroscopically by measuring the concentrations of the metals in solution before and after contact with the MST. Cytotoxic responses to MST were assessed using THP1 monocytes and succinate dehydrogenase activity. Monocytic activation by MST was assessed by TNFalpha secretion (ELISA) with or without lipopolysaccharide (LPS) activation. MST adsorbed Cd(II), Hg(II), and Au(III) under conditions similar to those in physiological systems. MST exhibited the highest affinity for Cd(II) followed by Hg(II) and Au (III). MST (up to 100 mg/L) exhibited only minor (<25% suppression of succinate dehydrogenase) cytotoxicity and did not trigger TNFalpha secretion nor modulate LPS-induced TNFalpha secretion from monocytes. MST exhibits high affinity for biometals with no significant biological liabilities in these introductory studies. MST deserves further scrutiny as a substance with the capacity to decontaminate biological environments or deliver metals or metal compounds for therapeutic applications.
Asunto(s)
Auranofina/química , Sistemas de Liberación de Medicamentos , Metales Pesados/química , Monocitos , Adsorción , Auranofina/uso terapéutico , Materiales Biocompatibles , Línea Celular , Descontaminación , Humanos , Intercambio Iónico , Lipopolisacáridos/farmacología , Lipopolisacáridos/toxicidad , Ensayo de Materiales , Metales Pesados/uso terapéutico , Monocitos/metabolismo , Monocitos/ultraestructura , Residuos Radiactivos , Succinato Deshidrogenasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: Effective partner management is critical in reducing the spread of bacterial sexually transmitted infections (STIs). The purpose of this study was to determine the relation between knowledge of partner treatment for a past STI and current infection in the index patient. METHODS: In a cross sectional analysis, 97 adolescent females sampled from community based health clinics reported that they had a past diagnosis of chlamydia or gonorrhoea in structured, face to face interviews. At the time of the interview, adolescents were also tested for chlamydia and gonorrhoea using urine based ligase chain reaction testing. RESULTS: 66% of the adolescents reported knowing that their partner was treated for the past infection. Those who knew their partner was treated were less likely to have a current infection, compared to those who did not know (11% v 30%, adjusted odds ratio and 95% confidence interval 4.46 (1.41 to 14.29), p<0.05). Correlates of not knowing the sex partner was treated included younger age and being in new sex partnership. CONCLUSIONS: Efforts to encourage young women to follow up directly with their partners regarding treatment may help to reduce repeat infections and further spread. Furthermore, alternative strategies such as patient delivered therapy may help with partner treatment in this vulnerable population.
Asunto(s)
Infecciones por Chlamydia/terapia , Gonorrea/terapia , Conocimientos, Actitudes y Práctica en Salud , Parejas Sexuales , Adolescente , Adulto , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/psicología , Estudios Transversales , Femenino , Gonorrea/diagnóstico , Gonorrea/psicología , Humanos , Oportunidad Relativa , Recurrencia , Factores de RiesgoRESUMEN
The transcription factor NFkappaB plays a key role in the tissue inflammatory response. Metal ions released into tissues from biomaterials (e.g., Au, Pd, Ni, Hg) are known to alter the binding of NFkappaB proteins to DNA, thereby modulating the effect of NFkappaB on gene activation and, ultimately, the tissue response to biomaterials. Little is known about the effect of these metals on key signaling steps prior to NFkappaB-DNA binding such as transcription factor activation or nuclear translocation, yet these steps are equally important to modulation of the pathway. Oxidative stress is known to alter NFkappaB proteins and is suspected to play a role in metal-induced NFkappaB signaling modulation. Our aim in the current study was to assess the effects of sublethal levels of Ni, Hg, Pd, and Au ions on NFkappaB activation and nuclear translocation in the monocyte, which is acknowledged as an important orchestrator of the biological response to materials and the pathogenesis of chronic disease. Sublethal concentrations of Au(III), Ni(II), Hg(II), and Pd(II) were added to cultures of human THP1 monocytic cells for 72 h. In parallel cultures, lipopolysaccharide (LPS) was added for the last 30 min to activate the monocytic cells. Then cellular cytoplasmic and nuclear proteins were isolated, separated by electrophoresis, and probed for IkappaBalpha degradation (activation) and NFkappaB p65 translocation. Protein levels were digitally quantified and statistically compared. The levels of reactive oxygen species (ROS) in the monocytic cells were measured as a possible mechanism of metal-induced NFkappaB modulation. Only Au(III) activated IkappaBalpha degradation by itself. Au(III) and Pd(II) enhanced LPS-induced IkappaBalpha degradation, but Hg(II) and Ni(II) suppressed it. Au(III), Ni(II), and Pd(II) activated p65 nuclear translocation without LPS, and all but Ni(II) enhanced LPS-induced translocation. Collectively, the results suggest that these metal ions alter activation and translocation of NFkappaB, each in a unique way at unique concentrations. Furthermore, even when these metals had no overt effects on signaling by themselves, all altered activation of signaling by LPS, suggesting that the biological effects of these metals on monocytic function may only be manifest upon activation. None of the metal ions elevated levels of ROS at 72 h, indicating that ROS were probably not direct modulators of the NFkappaB activation or translocation at this late time point.
Asunto(s)
Metales Pesados/farmacología , Monocitos/efectos de los fármacos , Monocitos/fisiología , FN-kappa B/fisiología , Transducción de Señal/efectos de los fármacos , Cationes Bivalentes , Línea Celular Tumoral , Oro/fisiología , Humanos , Proteínas I-kappa B/metabolismo , Immunoblotting , Mercurio/fisiología , Monocitos/metabolismo , Inhibidor NF-kappaB alfa , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Níquel/fisiología , Paladio/fisiología , Fosforilación , Transporte de Proteínas/fisiología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiologíaRESUMEN
The use of hydrophilic dental monomers in dentin bonding agents has vastly improved resin-dentin bond strengths, but incomplete polymerization of these monomers and their leaching into adjacent (pulpal) oral tissues has raised concerns about their biocompatibility. The sublethal effects of these resins are virtually unknown, but their electrophilic nature led to the hypothesis that they may alter cellular oxidative stress pathways. Glutathione balance between reduced (GSH) and oxidized (GSSG) is a major mechanism by which cells maintain redox balance and was therefore the focus of the current investigation. THP-1 human monocytic cells were exposed to hydroxyethyl methacrylate (HEMA), benzoyl peroxide (BPO), camphorquinone (CQ), or triethyelene glycol dimethacrylate (TEGDMA) for 24 h at sublethal doses, then GSH and GSSG levels were measured by means of Ellman's method adapted for cell culture. The results indicate that these dental resin compounds act at least partly via oxidative stress by increasing GSH levels at sublethal concentrations. However, the GSH-GSSG ratio was relatively unaffected. Only BPO altered the GSH-GSSG ratio at 24 h, again at sublethal levels (7.5-15 micromol/L). The results support the hypothesis that resin monomers act, at least in part, via oxidative stress, and that oxidative-stress pathways should be one focus of future investigations of monomer biocompatibility.
Asunto(s)
Recubrimientos Dentinarios/farmacología , Glutatión/metabolismo , Monocitos/fisiología , Estrés Oxidativo/fisiología , Butionina Sulfoximina/farmacología , Línea Celular , Resinas Compuestas/farmacología , Disulfuro de Glutatión/metabolismo , Glutatión Reductasa/metabolismo , Humanos , Metacrilatos/farmacología , Monocitos/efectos de los fármacos , Oxidación-Reducción , Polietilenglicoles/farmacología , Ácidos Polimetacrílicos/farmacologíaRESUMEN
The objective of this study was to quantify the ability of sublethal concentrations of several gold compounds to differentially modulate the monocytic secretion of key cytokines that are important in the etiology of rheumatic diseases. Human THP1 monocytic cells were exposed to the anti-rheumatic drugs auranofin (AF), gold sodium thiomalate (GSTM) or HAuCl4 (Au(III)) for 24-72 h. Succinate dehydrogenase (SDH) activity of the monocytes was used to determine sublethal concentrations. Monocytes were then exposed to sublethal concentrations of gold compounds for 72 h, and the activator lipopolysaccharide (LPS) was added (or not) to cultures for the last 6h. The secretion of IL6, IL8, IL10, and TNFalpha were measured in cell supernatants using ELISA. Cytokine secretion was compared among concentrations and gold compounds. SDH experiments established a sublethal concentration range of 0-75 microM for GSTM and Au(III) and 0-0.5 microM for AF. In cytokine experiments, none of the compounds alone activated secretion of any of the cytokines, but all differentially (50-440%, p<0.05) increased LPS-induced secretion of IL6 and IL8 over TNFalpha and IL10. In conclusion, sublethal concentrations of AF, GSTM, and Au(III) all may differentially modulate activation of monocytic cells, and this differential modulation may be important in the mechanisms of action of these compounds.
Asunto(s)
Antirreumáticos/toxicidad , Auranofina/toxicidad , Cloruros/toxicidad , Citocinas/metabolismo , Compuestos de Oro/toxicidad , Tiomalato Sódico de Oro/toxicidad , Monocitos/efectos de los fármacos , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Monocitos/metabolismo , Succinato Deshidrogenasa/metabolismoRESUMEN
Previous studies have reported that blue light (400-500 nm) inhibits cell mitochondrial activity. We investigated the hypothesis that cells with high energy consumption are most susceptible to blue-light-induced mitochondrial inhibition. We estimated cell energy consumption by population doubling time, and cell survival and growth by succinate dehydrogenase (SDH) activity. Six cell types were exposed to 5 or 60 J/cm(2) of blue light from quartz-tungsten-halogen (QTH), plasma-arc (PAC), or argon laser sources in monolayer culture. Post-light SDH activity correlated positively with population doubling time (R(2) = 0.91 for PAC, 0.76 for QTH, 0.68 for laser); SDH activity increased for cell types with the longest doubling times and was suppressed for cell types with shorter doubling times. Thus, light-induced exposure differentially affects SDH activity, cell survival, and growth, depending on cell energy consumption. Blue light may be useful as a therapeutic modulator of cell growth and survival.