Propiedades psicométricas de la versión al español del cuestionario “Barriers to Being Active Quiz”, entre estudiantes universitarios de Colombia

Objetivo: El cuestionario Barriers to Being Active Quiz (BBAQ), indaga las barreras para ser físicamente activo. El cuestionario fue traducido al español por el mismo equipo que desarrolló la versión inglésa original, pero carece de estudios de validez en la versión española. El objetivo de esta investigación fue evaluar las propiedades psicométricas del BBAQ (en la versión completa de 21 ítems), centrándose en la fiabilidad y validez. Material y métodos: Un total de 2.634 (1.462 mujeres y 1.172 varones; 18-30 años de edad) estudiantes universitarios completaron el cuestionario BBAQ-21. El alfa de Crombach se estimó como indicador de consistencia interna. El coeficiente de correlación intra-clase (CCI) y el grado de acuerdo se calcularon para evaluar la estabilidad temporal con un periodo de 7 días entre ambas administraciones como estimadores de la reproducibilidad. Se aplicó un análisis factorial exploratorio (AFE) y confirmatorio (AFC) para analizar la validez del BBAQ-21 ítems. Resultados: El BBAQ-21 mostró valores de un alfa de Cronbach entre 0,812 y 0,844 y un CCI entre el 0,46 y 0,87. El porcentaje de acuerdo por todos los conceptos individuales varió de 45 a 80%. El AFE determinó cuatro factores que explicaron el 52,90% de la varianza y el AFC mostró moderadas cargas factoriales. Conclusiones: Los resultados obtenidos en este cuestionario avalan la utilización de este instrumento con este tipo de muestra, desde el punto de vista de la fiabilidad y validez. El BBAQ-21 está disponible para evaluar las barreras para la actividad física en América Latina.

Statistical evaluation of an acute dermal toxicity test using the dermal fixed dose procedure

The conventional method for the assessment of acute dermal toxicity (OECD Test Guideline 402, 1987) uses death of animals as an endpoint to identify the median lethal dose (LD50). A new OECD Testing Guideline called the dermal fixed dose procedure (dermal FDP) is being prepared to provide an alternative to Test Guideline 402. In contrast to Test Guideline 402, the dermal FDP does not provide a point estimate of the LD50, but aims to identify that dose of the substance under investigation that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonised System of Classification and Labelling scheme (GHS). The dermal FDP has been validated using statistical modelling rather than by in vivo testing. The statistical modelling approach enables calculation of the probability of each GHS classification and the expected numbers of deaths and animals used in the test for imaginary substances with a range of LD50 values and dose-response curve slopes. This paper describes the dermal FDP and reports the results from the statistical evaluation. It is shown that the procedure will be completed with considerably less death and suffering than guideline 402, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LD50 value.

A statistical evaluation of the fixed dose procedure

The fixed-dose procedure (FDP) was introduced as OECD Test Guideline 420 in 1992, as an alternative to the conventional median lethal dose (LD50) test for the assessment of acute oral toxicity (OECD Test Guideline 401). The FDP uses fewer animals and causes less suffering than the conventional test, while providing information on the acute toxicity to allow substances to be ranked according to the EU hazard classification system. Recently the FDP has been revised, with the aim of providing further reductions and refinements, and classification according to the criteria of the Globally Harmonized Hazard Classification and Labelling scheme (GHS). This paper describes the revised FDP and analyses its properties, as determined by a statistical modelling approach. The analysis shows that the revised FDP classifies substances for acute oral toxicity generally in the same, or a more stringent, hazard class as that based on the LD50 value, according to either the GHS or the EU classification scheme. The likelihood of achieving the same classification is greatest for substances with a steep dose-response curve and median toxic dose (TD50) close to the LD50. The revised FDP usually requires five or six animals with two or fewer dying as a result of treatment in most cases.

Fitting models for the joint action of two drugs using SAS(R)

Combinations of drugs are increasingly being used for a wide variety of diseases and conditions. A pre-clinical study may allow the investigation of the response at a large number of dose combinations. In determining the response to a drug combination, interest may lie in seeking evidence of synergism, in which the joint action is greater than the actions of the individual drugs, or of antagonism, in which it is less. Two well-known response surface models representing no interaction are Loewe additivity and Bliss independence, and Loewe or Bliss synergism or antagonism is defined relative to these. We illustrate an approach to fitting these models for the case in which the marginal single drug dose-response relationships are represented by four-parameter logistic curves with common upper and lower limits, and where the response variable is normally distributed with a common variance about the dose-response curve. When the dose-response curves are not parallel, the relative potency of the two drugs varies according to the magnitude of the desired effect and the models for Loewe additivity and synergism/antagonism cannot be explicitly expressed. We present an iterative approach to fitting these models without the assumption of parallel dose-response curves. A goodness-of-fit test based on residuals is also described. Implementation using the SAS NLIN procedure is illustrated using data from a pre-clinical study. Copyright © 2007 John Wiley & Sons, Ltd.

A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans

Objective: To evaluate the bifidogenic efficacy of two inulin doses in healthy human adults. Design: A double-blind, placebo-controlled, crossover human study. Setting: Food Microbial Sciences Unit, The University of Reading, Reading, UK. Subjects: Thirty healthy volunteers, 15 men, 15 women ( age range 19-35). Interventions: Subjects consumed a chocolate drink containing placebo ( maltodextrin, 8 g/day), 5 g/day inulin and 8 g/day inulin for a 2-week treatment period. Each treatment was followed by a 1-week washout at the end of which volunteers progressed to the next treatment. Faecal samples were obtained at the start of the study ( baseline) and at the end of each treatment and washout period. Fluorescent in situ hybridization was used to monitor populations of Bifidobacterium genus, Bacteroides - Prevotella, Lactobacillus - Enterococcus and Clostridium perfringens - histolyticum subgroup. Results: Bifidobacterial levels increased significantly upon ingestion of both the low ( 9.78 +/- 0.29 log(10) cells/g faeces, P < 0.05) and the high inulin dose ( 9.79 +/- 0.38 log(10) cells/g faeces, P < 0.05) compared to placebo ( 9.64 +/- 0.23 log(10) cells/g faeces). Conclusions: Both inulin doses exhibited a bifidogenic effect but a higher volunteer percentage responded to the high dose. A dose response effect was not observed but the magnitude of increase in bifidobacteria levels depended on their initial numbers. The higher the initial concentrations the smaller was the increase upon ingestion of the active treatments. Sponsorship: Financial support for the completion of this project was provided by Sensus ( Roosendaal, The Netherlands).

Blood-clotting response tests for resistance to diphacinone and chlorophacinone in the Norway rat (Rattus norvegicus Berk.)

Resistance baselines were obtained for the first generation anticoagulant rodenticides chlorophacinone and diphacinone using laboratory, caesarian-derived Norway rats (Rattus norvegicus) as the susceptible strain and the blood clotting response test method. The ED99 estimates for a quantal response were: chlorophacinone, males 0.86 mg kg−1, females 1.03 mg kg−1; diphacinone, males 1.26 mg kg−1, females 1.60 mg kg−1. The dose-response data also showed that chlorophacinone was significantly (p<0.0001) more potent than diphacinone for both male and female rats, and that male rats were more susceptible than females to both compounds (p<0.002). The ED99 doses were then given to groups of five male and five female rats of the Welsh and Hampshire warfarin-resistant strains. Twenty-four hours later, prothrombin times were slightly elevated in both strains but all the animals were classified as resistant to the two compounds, indicating cross-resistance from warfarin to diphacinone and chlorophacinone. When rats of the two resistant strains were fed for six consecutive days on baits containing either diphacinone or chlorophacinone, many animals survived, indicating that their resistance might enable them to survive treatments with these compounds in the field.

Accounting for the economic risk, caused by variation in disease severity, in fungicide dose decisions: exemplified for Mycosphaerella graminicola on winter wheat

A method is presented to calculate economic optimum fungicide doses accounting for the risk-aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost, plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimises net costs on average across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept ‘high loss’ years one year in ten or one year in twenty (i.e. specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk-aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over three years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of ‘high loss’ years requires substantially higher doses to be applied to all crops. Disease resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Study of the gamma radiation response of watch glasses

Some dosimetric properties of watch glasses were studied applying the thermoluminescence technique. The watch glass samples were powdered, and the selected grains were mixed with Teflon (TM). The mixture was pressed and sintered to produce pellets of watch glass-Teflon (TM) composites. The glow curves of the pellets show two peaks at 130 and 195 degrees C. Reproducibility of TL response was estimated to have a maximum coefficient of variation of 4.0%. The dose-response curve is sublinear between 0.5 and 20.0kGy. The calibration curve is linear between 1.0Gy and 1.0kGy. The minimum detection limits were also determined. The gamma radiation dose response and the thermal stability of the materials were studied with the purpose to establish the best conditions of watch glasses for use in gamma radiation dosimetry. (C) 2007 Elsevier Ltd. All rights reserved.

Correlation between thermoluminescence sensitivity and crystallization temperatures of quartz: Potential application in geothermometry

The thermoluminescence (TL) characteristics of quartz are highly dependent of its thermal history. Based on the enhancement of quartz luminescence occurred after heating, some authors proposed to use quartz TL to recover thermal events that affected quartz crystals. However, little is know about the influence of the temperature of quartz crystallization on its TL characteristics. In the present study, we evaluate the TL sensitivity and dose response curves of hydrothermal and metamorphic quartz with crystallization temperatures from 209 +/- 15 to 633 +/- 27 degrees C determined through fluid inclusion and mineral chemistry analysis. The studied crystals present a cooling thermal history, which allow the acquiring of their natural TL without influence of heating after crystallization. The TL curves of the studied samples present two main components formed by different peaks overlapped around 110 C and 200-400 degrees C. The TL sensitivity in the 200-400 degrees C region increases linearly with the temperature of quartz crystallization. No relationship was observed between temperatures of quartz crystallization and saturation doses (<100 Gy). The elevated TL sensitivity of the high temperature quartz is attributed to the control exerted by the temperature of crystallization on the substitution of Si(4+) by ions such as Al(3+) and Ti(4+), which produce defects responsible for luminescence phenomena. The linear relationship observed between TL in the 200-400 degrees C region and crystallization temperature has potential use as a quartz geothermometer. The relative abundance of quartz in the earth crust and the easiness to measure TL are advantageous in relation to geothermometry methods based on chemistry of other minerals. (C) 2010 Elsevier Ltd. All rights reserved.

Inhibition Mechanism of Rat alpha(3)beta(4) Nicotinic Acetylcholine Receptor by the Alzheimer Therapeutic Tacrine

Nicotinic acetylcholine receptors (nAChRs) were studied in detail in the past regarding their interaction with therapeutic and drug addiction related compounds. Using fast kinetic whole-cell recording, we have now studied effects of tacrine, an agent used clinically to treat Alzheimer`s disease, on currents elicited by activation of rat alpha(3)beta(4) nAChR heterologously expressed in KX alpha(3)beta(4)R2 cells. Characterization of receptor activation by nicotine used as agonist revealed a K(d) of 23 +/- 0.2 mu M and 4.3 +/- 1.3 for the channel opening equilibrium constant, Phi(-1). Experiments were performed to investigate whether tacrine is able to activate the alpha(3)beta(4) nAChR. Tacrine did not activate whole-cell currents in KX alpha(3)beta(4)R2 cells but inhibited receptor activity at submicromolar concentration. Dose response curves obtained with increasing agonist or inhibitor concentration revealed competitive inhibition of nAChRs by tacrine, with an apparent inhibition constant, K(I), of 0.8 mu M. The increase of Phi(-1) in the presence of tacrine suggests that the drug stabilizes a nonconducting open channel form of the receptor. Binding studies with TCP and MK-801 ruled out tacrine binding to common allosteric sites of the receptor. Our study suggests a novel mechanism for action of tacrine on nAChRs besides inhibition of acetylcholine esterase.

Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors

The ruthenium NO donors of the group trans-[Ru(NO)(NH(3))(4)L](n+), where the ligand (L) is N-heterocyclic H(2)O, SO(3)(2 -), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC(50)(try)) and cytotoxicity data on mammalian V-79 cells (IC(50)(V79)), the in vitro therapeutic indices (TIs) (IC(50)(V79)/IC(50)(try)) for these compounds were calculated. Compounds that exhibited an in vitro TI of >= 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC(50)(try/epi) of <= 100 mu M were assayed in a mouse model for acute Chagas` disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) (isn, isonicotinamide) and trans-[Ru(NO)(NH3) 4imN](BF4) 3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD(50)) for both compounds are higher than 125 mu mol/kg, the in vivo TIs (LD(50)/ED(50)) of the compounds are 1,453 for trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and 658 for trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3). Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi -glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.

Smoking and Periodontal Disease: Clinical Evidence for an Association

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Can a Strychnos species be used as antiulcer agent? Ulcer healing action from alkaloid fraction of Strychnos pseudoquina St. Hil. (Loganiaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)