995 resultados para Toxicity Tests


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Report for the scientific sojourn carried out at Albert Einstein Institut in Germany, from April to July 2006.

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Clinical and serological follow up examinations were performed on 203 persons, from three to twenty years of age, from the otolaryngology department of a hospital in the city of Rio de Janeiro, with no symptomatology suggesting toxoplasmosis, but suffering from chronic tonsillitis. According to results obtained during the first indirect immunofluorescence tests, the patients were divided into following groups: Group I (non-reactive IgG and IgM), 98 persons (48.3%); Group II (1:16 ≤ IgG ≤ 1:256 and non-reactive IgM), 74 persons (36.5%); Group III (IgM ≥ 1:1024 and non-reactive IgM), 18 persons (8.8%), and Group IV (IgG and IgM reactive), 13 persons (6.4%). One to two years later, 131 (64.5%) of the 203 persons were reexamined by a second indirect immunofluorescence test. In the case of 66 persons (Group I) whose serum was non-reactive in the IgG and IgM classes during the first indirect immunofluorescence test, serum conversion was observed in aproximately 21.2%. in 65 individuals (49.6%), (Groups II, III and IV),with reactive serum in the IgG classes during the first indirect immunofluorescence test, the second reaction showed an increase in titres in 20% of the cases, a decrease in 67.7% of the cases, or no alterations in 12.3 of the cases. In the IgM class, all 131 sera were non-reactive at 116 dilution the second immunofluorescence test, including the 13 cases that had previously been reactive in the immunoglobulin class, Symptomatology suggesting toxoplasmosis was only observed in one case during the second testing, this patient's principal physical sign being hypertrophied lymph nodes. during this period, the Toxoplasma antibodies showed titres of IgG 1:32000 and non-reactive IgM, whilst one year previously, during the first test, these titres were IgG 1:1024 and IgM 1:64. Differences in the age, sex and skin coloring of patients were not statistically significant as regards alterations in the indirect immunofluorescence test titres.

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This paper tests for real interest parity (RIRP) among the nineteen major OECD countries over the period 1978:Q2-1998:Q4. The econometric methods applied consist of combining the use of several unit root or stationarity tests designed for panels valid under cross-section dependence and presence of multiple structural breaks. Our results strongly support the fulfillment of the weak version of the RIRP for the studied period once dependence and structural breaks are accounted for.

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Point-of-care (POC) tests offer potentially substantial benefits for the management of infectious diseases, mainly by shortening the time to result and by making the test available at the bedside or at remote care centres. Commercial POC tests are already widely available for the diagnosis of bacterial and viral infections and for parasitic diseases, including malaria. Infectious diseases specialists and clinical microbiologists should be aware of the indications and limitations of each rapid test, so that they can use them appropriately and correctly interpret their results. The clinical applications and performance of the most relevant and commonly used POC tests are reviewed. Some of these tests exhibit insufficient sensitivity, and should therefore be coupled to confirmatory tests when the results are negative (e.g. Streptococcus pyogenes rapid antigen detection test), whereas the results of others need to be confirmed when positive (e.g. malaria). New molecular-based tests exhibit better sensitivity and specificity than former immunochromatographic assays (e.g. Streptococcus agalactiae detection). In the coming years, further evolution of POC tests may lead to new diagnostic approaches, such as panel testing, targeting not just a single pathogen, but all possible agents suspected in a specific clinical setting. To reach this goal, the development of serology-based and/or molecular-based microarrays/multiplexed tests will be needed. The availability of modern technology and new microfluidic devices will provide clinical microbiologists with the opportunity to be back at the bedside, proposing a large variety of POC tests that will allow quicker diagnosis and improved patient care.

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This paper applies recently developed heterogeneous nonlinear and linear panel unit root tests that account for cross-sectional dependence to 24 OECD and 33 non-OECD countries’ consumption-income ratios over the period 1951–2003. We apply a recently developed methodology that facilitates the use of panel tests to identify which individual cross-sectional units are stationary and which are nonstationary. This extends evidence provided in the recent literature to consider both linear and nonlinear adjustment in panel unit root tests, to address the issue of cross-sectional dependence, and to substantially expand both time-series and cross sectional dimensions of the data analysed. We find that the majority (65%) of the series are nonstationary with slightly fewer OECD countries’ (61%) series exhibiting a unit root than non-OECD countries (68%).

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Is institutional quality a major driver of economic development? This paper tackles the question by focusing on the within-country variation of growth rates of GDP per capita. While previous attempts using this methodology have controlled for many of the standard de- terminants of the empirical growth literature, we argue that such ap- proach is not adequate if good institutions are the main reason behind decisions to invest in human or physical capital accumulation or to engage in international trade. Our regressions exclude the proximate causes of growth in order to estimate the overall e¤ect of institutional quality. Perhaps surprisingly, we nd no support for the thesis that institutional quality improves economic growth. These results encourage a reconsideration of the evidence provided elsewhere in the literature.

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As most metabolic studies are conducted in male animals, understanding the sex specificity of the underlying molecular pathways has been broadly neglected; for example, whether PPARs elicit sex-dependent responses has not been determined. Here we show that in mice, PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and immunity. In male mice, this effect was reproduced by the administration of a synthetic PPARalpha ligand. Using the steroid oxysterol 7alpha-hydroxylase cytochrome P4507b1 (Cyp7b1) gene as a model, we elucidated the molecular mechanism of this sex-specific PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggered the interaction of PPARalpha with GA-binding protein alpha (GABPalpha) bound to the target Cyp7b1 promoter. Histone deacetylase and DNA and histone methylases were then recruited, and the adjacent Sp1-binding site and histones were methylated. These events resulted in loss of Sp1-stimulated expression and thus downregulation of Cyp7b1. Physiologically, this repression conferred on female mice protection against estrogen-induced intrahepatic cholestasis, the most common hepatic disease during pregnancy, suggesting a therapeutic target for prevention of this disease.

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Report for the scientific sojourn at the National Institute for Public Health and the Environment (RIVM), Netherlands, from 2006 to 2008. This project aimed at creating scientific elements that could help deriving an integrated testing strategy for reproductive toxicity. Part of the project focused on the use of alternative tests for regulatory purposes. An in vitro-in vivo extrapolation method for embryotoxicity was proposed and evaluated. In vitro and in vivo dose descriptors were correlated; however, the scatter in the correlation was too large to allow an accurate estimation of an in vivo dose from an in vitro dose. The in vitro-in vivo extrapolation method together with toxicokinetic data was also applied to a category of substances (phthalates). Although based on a limited number of substances, the results suggested that in vitro-in vivo extrapolation for embryotoxicity is possible within a category of compounds if adequate toxicokinetic data is available. Because of the limitations that still remain in the use of alternative tests for reproductive toxicicity, other approaches to reduce animal testing were explored. Thus, a database of reproductive toxicity studies was created to retrospectively evaluate the comparative value of some studies or elements in a particular study. When compared to the subchronic toxicity study, the rat two-generation reproductive toxicity study had a considerable impact on the identification of hazard for reproductive toxicity, but not on the overall NOAEL. Among the two-generation studies included in our database, the second generation affected neither the overall NOAEL nor the critical effect. The rat and the rabbit developmental toxicity studies were, on average, similarly sensitive. However, for certain substances the developmental study in either one of the two species appeared to be more sensitive than in the other species.

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Recent risk sharing tests strongly reject the hypothesis of complete markets, because in the data: (1) the individual consumption comoves with income and (2) the consumption dispersion increases over the life cycle. In this paper, I revisit the implications of these risk sharing tests in the context of a complete market model with discount rate heterogeneity, which is extended to introduce the individual choices of effort in education. I .nd that a complete market model with discount rate heterogeneity can pass both types of the risk sharing tests. The endogenous positive correlation between income growth rate and patience makes the individual consumption comove with income, even if the markets are complete. I also show that this model is quantitatively admissible to account for both the observed comovement of consumption and income and the increase of consumption dispersion over the life cycle.

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Modern macroeconomic theory utilises optimal control techniques to model the maximisation of individual well-being using a lifetime utility function. Agents face choices over current and future consumption (with resultant implied savings decisions) seeking to maximise the present value of current plus future well-being. However, such inter-temporal welfare-maximising assumptions remain empirically untested. In the work presented here we test whether welfare was in (historical) fact maximised in the US between 1870-2000 and find empirical support for the optimising basis of growth theory, but only once a comprehensive view of what constitutes a country’s wealth or capital is taken into account.

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En el present estudi s’ha fet un seguiment baromètric de la producció de biogàs de tres compostos farmacèutics mitjançant tests de degradació anaeròbia. El llot del digestor anaerobi de l’estació depuradora d’aigües residuals (EDAR) de Granollers s’ha emprat com a inòcul. En un primer experiment, s’ha fet l’estudi de l’etapa metanogènica, amb metanol com a substrat i les concentracions de 5, 10 i 20 mg·L-1 d’àcid clofíbric (CLOFI, regulador lípid), ibuprofè (IBU, anti-inflamatori) i carbamazepina (CARBA, antiepilèptic/analgèsic). En un segon experiment, s’ha estudiat l’etapa acetogènica, amb àcid propiònic com a substrat i amb concentracions de 20 i 100 mg·L-1 dels mateixos fàrmacs. Per una banda, en el primer experiment, no s’ha observat degradació dels fàrmacs i cap d’ells presenta toxicitat pel llot anaerobi. CARBA i IBU s’adsorbeixen majoritàriament a la fase sòlida. Per altra banda, en l’etapa acetogènica ni CARBA ni IBU s’han degradat i tampoc presenten toxicitat en cap de les concentracions provades. Com en el cas anterior, la majoria d’aquests fàrmacs queda adsorbit en el llot. En canvi, CLOFI es degrada en 100 mg·L-1 de concentració donant com a producte intermedi un metabòlit.

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The passive haemagglutination (PHA) test, enzyme-linked immunosorbent assay (ELISA) and the dot enzyme-immunosorbent assay (DOT-ELISA) were used to detect the levels of IgG antibodies against the Fraction 1 (F1) antigen of Yersinia pestis in sera of plague-infected patients from Northeast Brazil. Twenty three selected PHA-positive sera of subjects with bacteriological confirmation of plague were also positive in the DOT-ELISA but only 19 were detected by the conventional ELISA technique. Another group of 186 serum samples from subjects diagnosed as plague-infected by clinical and epidemiological parameters, but PHA-negative, were screened with DOT-ELISA and 11 gave positive results. The specificity of the assays on the serological detection of plague was confirmed in inhibition tests using purified F1 antigen. These results suggest that DOT-ELISA can be an useful, simple and more sensitive alternative for the serodiagnosis of plague in Northeast Brazil.

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The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.