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1.
Nat Commun ; 13(1): 3448, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35705544

RESUMEN

Sediment, nutrients, organic carbon and pollutants are funnelled down submarine canyons from continental shelves by sediment-laden flows called turbidity currents, which dominate particulate transfer to the deep sea. Post-glacial sea-level rise disconnected more than three quarters of the >9000 submarine canyons worldwide from their former river or long-shore drift sediment inputs. Existing models therefore assume that land-detached submarine canyons are dormant in the present-day; however, monitoring has focused on land-attached canyons and this paradigm remains untested. Here we present the most detailed field measurements yet of turbidity currents within a land-detached submarine canyon, documenting a remarkably similar frequency (6 yr-1) and speed (up to 5-8 ms-1) to those in large land-attached submarine canyons. Major triggers such as storms or earthquakes are not required; instead, seasonal variations in cross-shelf sediment transport explain temporal-clustering of flows, and why the storm season is surprisingly absent of turbidity currents. As >1000 other canyons have a similar configuration, we propose that contemporary deep-sea particulate transport via such land-detached canyons may have been dramatically under-estimated.


Asunto(s)
Sedimentos Geológicos , Ríos , Estaciones del Año
2.
Eur J Appl Physiol ; 119(3): 645-652, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30591963

RESUMEN

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death worldwide. Many risk factors for CVD can be modified pharmacologically; however, uptake of medications is low, especially in asymptomatic people. Exercise is also effective at reducing CVD risk, but adoption is poor with time-commitment and cost cited as key reasons for this. Repeated remote ischaemic preconditioning (RIPC) and isometric handgrip (IHG) training are both inexpensive, time-efficient interventions which have shown some promise in reducing blood pressure (BP) and improving markers of cardiovascular health and fitness. However, few studies have investigated the effectiveness of these interventions in premenopausal women. METHOD: Thirty healthy females were recruited to twelve supervised sessions of either RIPC or IHG over 4 weeks, or acted as non-intervention controls (CON). BP measurements, flow-mediated dilatation (FMD) and cardiopulmonary exercise tests (CPET) were performed at baseline and after the intervention period. RESULTS: IHG and RIPC were both well-tolerated with 100% adherence to all sessions. A statistically significant reduction in both systolic (- 7.2 mmHg) and diastolic (- 6 mmHg) BP was demonstrated following IHG, with no change following RIPC. No statistically significant improvements were observed in FMD or CPET parameters in any group. CONCLUSIONS: IHG is an inexpensive and well-tolerated intervention which may improve BP; a key risk factor for CVD. Conversely, our single arm RIPC protocol, despite being similarly well-tolerated, did not elicit improvements in any cardiorespiratory parameters in our chosen population.


Asunto(s)
Capacidad Cardiovascular/fisiología , Enfermedades Cardiovasculares/terapia , Ejercicio Físico/fisiología , Contracción Isométrica/fisiología , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/fisiopatología , Endotelio Vascular/fisiología , Femenino , Fuerza de la Mano/fisiología , Humanos , Hipertensión/fisiopatología , Persona de Mediana Edad , Vasodilatación/fisiología
3.
Vaccine ; 35(31): 3889-3896, 2017 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-28606813

RESUMEN

In recent years concern has mounted regarding the possibility of a re-emergence of smallpox through biowarfare or bioterrorism. There is also concern over the incidence of human monkeypox in endemic areas and the potential for monkeypox to be accidentally transported to non-endemic areas. In the event of re-emergence of smallpox or emergence of monkeypox, the accepted route of administration for live replicating smallpox vaccine is dermal scarification, which generates a virus-shedding lesion that persists for several days at the vaccination site. The lesion is a potential source of contact transmission of vaccine to individuals who may be contra-indicated for receipt of the live vaccine. In this study, we compare dermal scarification with intramuscular vaccination for replicating smallpox vaccine in a mouse lethal challenge model. Comparisons are made over multiple vaccine and challenge doses and data recorded for lethality, disease severity, and antibody responses. Qualitative and quantitative differences between the two routes are observed, and for the intramuscular route the febrile response is not suppressed after subsequent virulent vaccinia virus challenge. However both routes generate an immune response and protect from severe disease and death. Although dermal scarification is the preferred route of vaccination for the general population, intramuscular vaccination may be an option for people who are not contraindicated for the live vaccine, but who are close contacts of people who are contraindicated for the live vaccine, in an emergency situation.


Asunto(s)
Vacuna contra Viruela/administración & dosificación , Vacuna contra Viruela/inmunología , Virus Vaccinia/inmunología , Vaccinia/prevención & control , Administración Cutánea , Animales , Modelos Animales de Enfermedad , Femenino , Inyecciones Intramusculares , Ratones Endogámicos BALB C , Análisis de Supervivencia , Resultado del Tratamiento , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología
4.
Water Res ; 113: 207-214, 2017 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-28214776

RESUMEN

Nitrite, in equilibrium with free nitrous acid (FNA), can inhibit both aerobic and anaerobic growth of microbial communities through bactericidal activities that have considerable potential for control of microbial growth in a range of water systems. There has been much focus on the effect of nitrite/FNA on anaerobic metabolism and so, to enhance understanding of the metabolic impact of nitrite/FNA on aerobic metabolism, a study was undertaken with a model denitrifying bacterium Paracoccus denitrificans PD1222. Extracellular nitrite inhibits aerobic growth of P. denitrificans in a pH-dependent manner that is likely to be a result of both nitrite and free nitrous acid (pKa = 3.25) and subsequent reactive nitrogen oxides generated from the intracellular passage of FNA into P. denitrificans. Increased expression of a gene encoding a flavohemoglobin protein (Fhp) (Pden_1689) was observed in response to extracellular nitrite. Construction and analysis of a deletion mutant established Fhp to be involved in endowing nitrite/FNA resistance at high extracellular nitrite concentrations. Global transcriptional analysis confirmed nitrite-dependent expression of fhp and indicated that P. denitrificans expressed a number of stress response systems associated with protein, DNA and lipid repair. It is therefore suggested that nitrite causes a pH-dependent stress response that is due to the production of associated reactive nitrogen species, such as nitric oxide from the internalisation of FNA.


Asunto(s)
Nitritos/metabolismo , Paracoccus denitrificans , Desnitrificación , Óxido Nítrico/metabolismo , Oxidación-Reducción
6.
Eur J Clin Microbiol Infect Dis ; 35(12): 2033-2036, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27614748

RESUMEN

The capacity of absorbent beads in BacT/ALERT® FA Plus and BACTEC® Aerobic/F Plus blood culture bottles to bind and neutralize antibiotics was compared. Binding was established using reverse-phase HPLC, and inactivation was based on the recovery of susceptible test stains from simulated blood cultures. The FA Plus medium demonstrated more rapid and better overall binding kinetics for each drug tested, resulting in significantly better overall recovery rates. Differences in time to detection favored the FA Plus medium for three drug/organism combinations and Aerobic/F Plus for two.


Asunto(s)
Adsorción , Antibacterianos/aislamiento & purificación , Cultivo de Sangre/métodos , Medios de Cultivo/química , Manejo de Especímenes/métodos , Antibacterianos/análisis , Cromatografía Líquida de Alta Presión , Humanos , Cinética , Factores de Tiempo
7.
Adv Microb Physiol ; 68: 353-432, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27134026

RESUMEN

Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nitric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the application of synthetic nitrogen-containing fertilizers. Thus, mitigation strategies must be developed which increase (or at least do not negatively impact) on agricultural efficiency whilst decrease the levels of N2O released. This aim is particularly important in the context of the ever expanding population and subsequent increased burden on the food chain. More than two-thirds of N2O emissions from soils can be attributed to bacterial and fungal denitrification and nitrification processes. In ammonia-oxidizing bacteria, N2O is formed through the oxidation of hydroxylamine to nitrite. In denitrifiers, nitrate is reduced to N2 via nitrite, NO and N2O production. In addition to denitrification, respiratory nitrate ammonification (also termed dissimilatory nitrate reduction to ammonium) is another important nitrate-reducing mechanism in soil, responsible for the loss of nitrate and production of N2O from reduction of NO that is formed as a by-product of the reduction process. This review will synthesize our current understanding of the environmental, regulatory and biochemical control of N2O emissions by nitrate-reducing bacteria and point to new solutions for agricultural GHG mitigation.


Asunto(s)
Amoníaco/metabolismo , Bacterias/metabolismo , Desnitrificación/fisiología , Restauración y Remediación Ambiental/métodos , Nitratos/metabolismo , Óxido Nitroso/metabolismo , Fertilizantes , Calentamiento Global/prevención & control , Hidroxilamina/química , Nitrificación/fisiología , Oxidación-Reducción , Oxidorreductasas/metabolismo , Suelo/química
8.
J Fish Biol ; 87(4): 1118-26, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26377954

RESUMEN

Evidence is presented from publicly available remotely operated vehicle (ROV) footage that suggests deep-water ranging in ocean sunfishes (family Molidae) is more common than typically thought, including a new maximum depth recorded for the southern sunfish Mola ramsayi.


Asunto(s)
Conducta Animal , Ecosistema , Tetraodontiformes/fisiología , Animales , Océanos y Mares , Densidad de Población , Dinámica Poblacional
9.
J Hum Nutr Diet ; 28(3): 246-61, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24852456

RESUMEN

BACKGROUND: Most national surveys examining diet leave large segments of the Aboriginal population under-represented. The present study aimed to: (i) review primary research studies that investigated the dietary intakes of Canadian school-aged Aboriginal youths; (ii) summarise the tools and methodologies currently used to measure diet in this population; and (iii) identify knowledge gaps and suggest areas of future research. METHODS: A systematic review of research published between January 2004 and January 2014 related to the diets of Canadian school-aged (6-18 years) Aboriginal youths was undertaken, including Medline, Scopus, ERIC, Web of Science and Google Scholar databases. Studies were summarised based on purpose, year, sample population, setting, dietary assessment method and main findings. RESULTS: Twenty-four studies were reviewed, all of which were cross-sectional in design. Most (n = 16; 67%) were from Ontario or Quebec, investigated the diets of First Nations (n = 21; 88%) youths and took place in remote or isolated settings (n = 18; 75%). Almost all of the studies used the 24-h recall to assess intake (n = 19; 79%), of which 89% used a single recall. The findings suggest that the diets of Aboriginal youths could be improved. Of particular concern are inadequate intakes of vegetables and fruit, milk and alternatives, fibre, folate, vitamin A, vitamin C, calcium and vitamin D, concomitant with an excess consumption of sugar sweetened beverages, snacks and fast foods. Traditional foods remain important but tend to be consumed infrequently. CONCLUSIONS: The diets of Canadian Aboriginal youths are energy-dense and nutrient-poor. The diets of Inuit and Métis youths, in particular, and perceptions of a balanced diet warrant further investigation.


Asunto(s)
Dieta , Indígenas Norteamericanos , Inuk , Estudiantes , Adolescente , Animales , Bebidas , Canadá , Niño , Estudios Transversales , Productos Lácteos , Registros de Dieta , Fibras de la Dieta , Sacarosa en la Dieta , Ingestión de Energía , Conducta Alimentaria , Frutas , Humanos , Memoria a Corto Plazo , Evaluación Nutricional , Bocadillos , Verduras , Vitaminas
10.
Rural Remote Health ; 13(3): 2498, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24033103

RESUMEN

INTRODUCTION: Prevalence rates of overweight and obesity in Canada have risen rapidly in the past 20 years. Concurrent with the obesity epidemic, sleep time and physical activity levels have decreased among youth. Aboriginal youth experience disproportionately high obesity prevalence but there is inadequate knowledge of contributing factors. This research aimed to examine sleep and screen time behavior and their relationship to Body Mass Index (BMI) in on-reserve First Nations youth from Ontario, Canada. METHODS: This was an observational population-based study of cross-sectional design. Self-reported physical activity, screen time, and lifestyle information was collected from 348 youth aged 10-18 years residing in five northern, remote First Nations communities and one southern First Nations community in Ontario, Canada, from October 2004 to June 2010. Data were collected in the school setting using the Waterloo Web-based Eating Behaviour Questionnaire. Based on self-reported height and weight, youth were classified normal (including underweight), overweight and obese according to BMI. Descriptive cross-tabulations and Pearson's χ² tests were used to compare screen time, sleep habits, and physical activity across BMI categories. RESULTS: Participants demonstrated low levels of after-school physical activity, and screen time in excess of national guidelines. Overall, 75.5% reported being active in the evening three or less times per week. Approximately one-quarter of the surveyed youth watched more than 2 hours of television daily and 33.9% spent more than 2 hours on the internet or playing video games. For boys, time using the internet/video games (p=0.022) was positively associated with BMI category, with a greater than expected proportion of obese boys spending more than 2 hours using the internet or video games daily (56.7%). Also for boys, time spent outside after school (p=0.033) was negatively associated with BMI category, with a lesser than expected proportion spending 'most of the time' outside (presumably being active) after school. These relationships were not observed in girls. Adjusted standardized residuals suggest a greater than expected proportion of obese individuals had a television in their bedroom (66.7%) as compared with the rest of the population. CONCLUSIONS: The current study adds to the limited information about contributors to overweight and obesity in First Nations youth living on-reserve in Canada. Concerns about inadequate sleep, excess screen time, and inadequate physical activity mirror those of the general population. Further investigation is warranted to improve the understanding of how various lifestyle behaviors influence overweight, obesity, and the development of chronic disease among First Nations youth. Initiatives to reduce screen time, increase physical activity, and encourage adequate sleep among on-reserve First Nations youth are recommended.


Asunto(s)
Índice de Masa Corporal , Ejercicio Físico , Indígenas Norteamericanos/estadística & datos numéricos , Sobrepeso/etnología , Adolescente , Niño , Femenino , Humanos , Internet , Masculino , Obesidad/etnología , Ontario/epidemiología , Prevalencia , Conducta Sedentaria/etnología , Sueño
11.
J Perinatol ; 30 Suppl: S2-5, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20877403

RESUMEN

The provision of appropriate nutritional support is an essential part of the primary and adjunctive management of many gastrointestinal (GI) disorders in neonatology and pediatrics. Few conditions in neonatology pose as great a challenge as intestinal failure or short bowel syndrome (SBS). The latter, SBS, is a complex disorder affecting normal intestinal physiology with nutritional, metabolic and infectious consequences. It is a result of the alteration of intestinal digestion and absorption following extensive bowel resection. Medical management of SBS is a very labor-intensive problem. Nutritional support and monitoring are of paramount importance, and long-term morbidity and mortality will depend on recognition and careful management of associated complications. With the increased use of intestine or intestine-liver transplant, maintaining these infants in good 'health' to allow transplantation will go a long way in achieving good long-term outcomes.


Asunto(s)
Apoyo Nutricional , Síndrome del Intestino Corto , Insuficiencia de Crecimiento/etiología , Alimentos Formulados/efectos adversos , Alimentos Formulados/análisis , Alimentos Formulados/normas , Insuficiencia Hepática/etiología , Insuficiencia Hepática/terapia , Humanos , Lactante , Recién Nacido , Absorción Intestinal/fisiología , Intestino Delgado/patología , Intestino Delgado/fisiología , Intestino Delgado/cirugía , Trasplante de Hígado , Micronutrientes/deficiencia , Leche Humana , Monitoreo Fisiológico , Apoyo Nutricional/efectos adversos , Apoyo Nutricional/métodos , Nutrición Parenteral Total en el Domicilio , Complicaciones Posoperatorias , Hidrolisados de Proteína/uso terapéutico , Síndrome del Intestino Corto/etiología , Síndrome del Intestino Corto/metabolismo , Síndrome del Intestino Corto/mortalidad , Síndrome del Intestino Corto/terapia , Resultado del Tratamiento
12.
Vaccine ; 26(16): 2010-9, 2008 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-18342996

RESUMEN

In a previous study, signature sequence mutagenesis (SSM) was used to identify a mutant with a disruption of the gene encoding the metabolic factor, dihydrolipoamide dehydrogenase, and that mutant was designated Mg 7. The current study assessed the safety, immunogenicity and efficacy of Mg 7 in comparison to two commercially available vaccines (ts-11 and F) as well as a laboratory vaccine strain, GT5. Intratracheal vaccination of chickens with all four attenuated mutants induced varying levels of protection against intratracheal challenge with virulent Mycoplasma gallisepticum strain R(low). Mg 7 vaccinated chickens rapidly cleared the challenge strain, had lower histopathologic tracheal lesion scores when compared to unvaccinated chickens, and mounted a strong humoral anti-M. gallisepticum-specific IgG response. The IgG levels increased 2- to 3-fold upon R(low) challenge. Mg 7 induced a greater level of protection against intratracheal R(low) challenge than that observed with the other three attenuated strains, as evidenced by a lower recovery of R(low) from tracheas and lower histopathologic lesion scores in tracheas and air sacs. Based on these findings, Mg 7 appears to have good potential as a safe and effective vaccine for the prevention of avian mycoplasmosis.


Asunto(s)
Vacunas Bacterianas/administración & dosificación , Infecciones por Mycoplasma/veterinaria , Mycoplasma gallisepticum/inmunología , Enfermedades de las Aves de Corral/prevención & control , Infecciones del Sistema Respiratorio/veterinaria , Vacunación , Sacos Aéreos/patología , Animales , Anticuerpos Antibacterianos/sangre , Pollos , Dihidrolipoamida Deshidrogenasa/genética , Femenino , Mutación , Infecciones por Mycoplasma/patología , Infecciones por Mycoplasma/prevención & control , Mycoplasma gallisepticum/enzimología , Mycoplasma gallisepticum/genética , Enfermedades de las Aves de Corral/patología , Mucosa Respiratoria/patología , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/prevención & control , Tráquea/patología , Vacunas Atenuadas/administración & dosificación
13.
Vaccine ; 25(1): 34-42, 2007 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-16950548

RESUMEN

International concern over the potential consequences of a Bioterrorist or Biowarfare associated release of variola virus have prompted renewed interest in the vaccines for smallpox. The traditional live, replicating vaccine strains are subject to novel safety concerns associated with historical production methods in domesticated ruminants and the additional hazards that vaccinia virus poses for people with immune system abnormalities or a history of eczematous skin conditions. In this study we have examined the longevity and efficacy of immunity induced by a non-replicating smallpox vaccine candidate, modified vaccinia Ankara (MVA) in a murine model using intranasal and aerosol routes of infection. Two-step vaccinations of MVA followed by traditional Lister vaccine are compared with either Lister alone or MVA alone, and the longevity of the protection induced by MVA is assessed. MVA is found to be broadly similar to Lister. Although protection is shown to decay with time, when administered at a standard human dose the longevity of protection induced by MVA is comparable to that induced by Lister.


Asunto(s)
Vacuna contra Viruela/administración & dosificación , Viruela/prevención & control , Virus Vaccinia/genética , Virus Vaccinia/inmunología , Administración Intranasal , Aerosoles , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Viruela/inmunología , Vacuna contra Viruela/inmunología , Vacunación/métodos , Virus Vaccinia/patogenicidad , Pérdida de Peso
14.
Vaccine ; 23(27): 3500-7, 2005 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-15855008

RESUMEN

There is currently considerable concern about the vulnerability of human populations to biowarfare or bioterrorist attacks with variola virus (VARV). Traditional smallpox vaccines were manufactured using the lymph of ruminants infected with the vaccinia virus (VACV). However, these production methods do not meet current standards for vaccines, especially since the emergence of transmissable spongiform encephalopathies in domesticated ruminants. This study has examined the protective efficacy of the Lister (Elstree) vaccine strain from various sources in a murine lethal challenge model. Considerable variation in efficacy is observed between the Lister material obtained from the American Type Culture Collection (ATCC) and the same strain obtained from vaccine stockpiles. A new, tissue-culture derived Lister vaccine is assessed against a bench-mark of multiple lots from a historical stockpile of the traditional vaccine. Apparent qualitative differences are observed between historical and new vaccines. Statistically significant differences are observed between different batches of the traditional vaccine, and the efficacy of the tissue-culture produced vaccine falls within this range.


Asunto(s)
Modelos Animales , Vacuna contra Viruela/administración & dosificación , Virus Vaccinia/fisiología , Vaccinia/prevención & control , Replicación Viral/fisiología , Administración Intranasal , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/inmunología , Femenino , Inmunización Secundaria , Ratones , Ratones Endogámicos BALB C , Conejos , Vacuna contra Viruela/inmunología , Vaccinia/fisiopatología , Virus Vaccinia/inmunología , Pérdida de Peso/inmunología
15.
Vaccine ; 22(25-26): 3358-66, 2004 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-15308360

RESUMEN

DNA vaccines might offer an alternative to the live smallpox vaccine in providing protective efficacy in an orthopoxvirus (OPV) lethal respiratory challenge model. BALB/c mice were immunised with DNA vaccines coding for 10 different single vaccinia virus (VACV) membrane proteins. After an intranasal challenge with the VACV IHD strain, three gene candidates B5R, A33R and A27L produced > or =66% survival. The B5R DNA vaccine consistently produced 100% protection and exhibited greatest efficacy after three 50 microg intramuscular doses in this model. Sero-conversion to these vaccines was often inconsistent, implying that antibody itself was not a correlate of protection. The B5R DNA vaccine induced a strong and consistent gamma interferon (IFNgamma) response in BALB/c mice given a single DNA vaccine dose. Strong IFNgamma responses were also measured in pTB5R immunised C57BL6 mice deficient for MHC class I molecules, suggesting that the memory response was mediated by a CD4+ T cell population.


Asunto(s)
Virus Vaccinia/genética , Virus Vaccinia/inmunología , Vaccinia/prevención & control , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/genética , Vacunas Virales/inmunología , Administración Intranasal , Animales , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/biosíntesis , Línea Celular , Femenino , Genes MHC Clase I/genética , Inmunidad Celular/inmunología , Memoria Inmunológica/inmunología , Interferón gamma/análisis , Interferón gamma/biosíntesis , Interleucina-5/análisis , Interleucina-5/biosíntesis , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Pruebas de Neutralización , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/inmunología , Vacunas de ADN/inmunología , Vaccinia/virología , Virus Vaccinia/crecimiento & desarrollo
17.
Hum Gene Ther ; 11(18): 2493-513, 2000 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-11119421

RESUMEN

A major limitation associated with systemic administration of cationic lipid:plasmid DNA (pDNA) complexes is the vector toxicity at the doses necessary to produce therapeutically relevant levels of transgene expression. Systematic evaluation of these toxicities has revealed that mice injected intravenously with cationic lipid:pDNA complexes develop significant, dose-dependent hematologic and serologic changes typified by profound leukopenia, thrombocytopenia, and elevated levels of serum transaminases indicative of hepatocellular necrosis. Vector administration also induced a potent inflammatory response characterized by complement activation and the induction of the cytokines IFN-gamma, TNF-alpha, IL-6, and IL-12. These toxicities were found to be transient, resolving with different kinetics to pretreatment levels by 14 days posttreatment. The toxic syndrome observed was independent of the cationic lipid:pDNA ratio, the cationic lipid species, and the level of transgene expression attained. Mechanistic studies determined that neither the complement cascade nor TNF-alpha were key mediators in the development of these characteristic toxicities. Administration of equivalent doses of the individual vector components revealed that cationic liposomes or pDNA alone did not generate the toxic responses observed with cationic lipid:pDNA complexes. Only moderate leukopenia was associated with administration of cationic liposomes or pDNA alone, while only mild thrombocytopenia was noted in pDNA-treated animals. These results establish a panel of objective parameters that can be used to quantify the acute toxicities resulting from systemic administration of cationic lipid:pDNA complexes, which in turn provides a means to compare the therapeutic indices of these vectors.


Asunto(s)
Cationes/toxicidad , Terapia Genética/efectos adversos , Lípidos/genética , Lípidos/toxicidad , Plásmidos/toxicidad , Animales , Plaquetas/metabolismo , Proteínas del Sistema Complemento/metabolismo , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Femenino , Inflamación/metabolismo , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Cinética , Leucocitos/metabolismo , Leucopenia/inducido químicamente , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Necrosis , Trombocitopenia/inducido químicamente , Factores de Tiempo , Transaminasas/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
18.
J Behav Health Serv Res ; 27(1): 47-59, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10695240

RESUMEN

This study investigated level of restrictiveness of living arrangements and number of days in out-of-family care at six months postintake, based on the Child and Adolescent Functional Assessment Scale (CAFAS), the Child Behavior Checklist (CBCL), gender, age, and level of family income at intake. It was composed of youths who met the criteria for serious emotional disturbance (SED) and were for the most part living in families that are described as socioeconomically disadvantaged. A multinomial logit model was used in the analysis of level of restrictiveness of living arrangements, and an ordinary least squares (OLS) regression model was conducted on number of days in out-of-family care. The CAFAS score at intake was found to be a significant predictor of service utilization between intake and six months and was a more consistent predictor than the CBCL. Results suggest that the CAFAS can be used to match service needs with resource allocation and to monitor performance-based outcome indicators.


Asunto(s)
Servicios de Salud del Adolescente/estadística & datos numéricos , Síntomas Afectivos/terapia , Servicios de Salud del Niño/estadística & datos numéricos , Servicios de Salud Mental/estadística & datos numéricos , Adolescente , Servicios de Salud del Adolescente/organización & administración , Niño , Conducta Infantil , Servicios de Salud del Niño/organización & administración , Humanos , Modelos Logísticos , Servicios de Salud Mental/organización & administración , Pruebas Psicológicas , Análisis de Regresión
19.
Prof Nurse ; 16(1): 835-8, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12029720

RESUMEN

'Bladder washout' is a misnomer, as it is the catheter that is being washed. Urinary catheters can cause significant physical and psychological problems. Although nurses are responsible for urinary catheter maintenance, there is a lack of knowledge in some areas. Some urological practices have been based on historical practice rather than evidence.


Asunto(s)
Vejiga Urinaria/fisiología , Cateterismo Urinario/enfermería , Infecciones Urinarias/prevención & control , Humanos , Atención de Enfermería/normas , Irrigación Terapéutica , Cateterismo Urinario/efectos adversos , Infecciones Urinarias/etiología
20.
Acta Virol ; 44(3): 151-6, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11155357

RESUMEN

Although it is unlikely that large-scale vaccination against smallpox will ever be required again, it is conceivable that the need may arise to vaccinate against a human orthopoxvirus infection. A possible example could be the emergence of monkey poxvirus (MPV) as a significant human disease in Africa. Vaccinia virus (VV) recombinants, genetically modified to carry the immunogenic proteins of other pathogenic organisms, have potential use as vaccines against other diseases present in this region. The immune response to parental wild-type (wt) or recombinant VV was examined by binding and functional assays, relevant to protection: total IgG, IgG subclass profile, B5R gene product (gp42)-specific IgG, neutralizing antibodies and class 1-mediated cytotoxic lymphocyte activity. There was a substantial reduction in the immune response to VV after scarification with about 10(8) PFU of recombinant as compared to wt virus. These data suggest that to achieve the levels of immunity associated with protection against human orthopoxvirus infection, and to control a possible future outbreak of orthopoxvirus disease, the use of wt VV would be necessary.


Asunto(s)
Timidina Quinasa/genética , Virus Vaccinia/inmunología , Animales , Especificidad de Anticuerpos/inmunología , Antígenos Virales/inmunología , Femenino , Inmunoglobulina G/sangre , Glicoproteínas de Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Mutación , Pruebas de Neutralización , Viruela/inmunología , Viruela/prevención & control , Linfocitos T Citotóxicos/inmunología , Vacunación , Vacunas Sintéticas/inmunología , Virus Vaccinia/genética , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/inmunología
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