The azo dye Disperse Orange 1 induces DNA damage and cytotoxic effects but does not cause ecotoxic effects in Daphnia similis and Vibrio fischeri

Azo dyes constitute the largest group of colorants used in industry and can pass through municipal waste water plants nearly unchanged due to their resistance to aerobic treatment, which potentially exposes humans and local biota to adverse effects. Unfortunately, little is known about their environmental fate. Under anaerobic conditions, some azo dyes are cleaved by microorganisms forming potentially carcinogenic aromatic amines. In the present study, the azo dye Disperse Orange 1, widely used in textile dyeing, was tested using the comet, Salmonella/microsome mutagenicity, cell viability, Daphnia similis and Microtox (R) assays. The human hepatoma cell line (HepG2) was used in the comet assay and for cell viability. In the mutagenicity assay. Salmonella typhimurium strains with different levels of nitroreductase and o-acetyltransferase were used. The dye showed genotoxic effects with respect to HepG2 cells at concentrations of 0.2, 0.4, 1.0, 2.0 and 4.0 mu g/mL. In the mutagenicity assay, greater responses were obtained with the strains TA98 and YG1041, suggesting that this compound mainly induces frameshift mutations. Moreover, the mutagenicity was greatly enhanced with the strains overproducing nitroreductase and o-acetyltransferase, showing the importance of these enzymes in the mutagenicity of this dye. In addition, the compound induced apoptosis after 72 h in contact with the HepG2 cells. No toxic effects were observed for either D. similis or Vibrio fischeri. (C) 2011 Elsevier B.V. All rights reserved.

The effects of chronic exposure to traffic derived air pollution on the ocular surface

Objectives: The purpose of this study was to explore the clinical relevance of chronic exposure to ambient levels of traffic derived air pollution on the ocular surface. Methods: A panel study involving 55 volunteers was carried out in Sao Paulo, Brazil. We measured the mean individual levels of nitrogen dioxide (NO(2)) exposure for 7 days. All subjects answered the Ocular Symptom Disease Index (OSDI) and a symptoms inventory. Subsequently, subjects underwent Schirmer I test, biomicroscopy, vital staining and tear breakup time (TOUT) assessment. Subject`s mean daily exposure to NO(2) was categorized in quartiles. Statistical analysis was performed using one-way ANOVA, Tukey HSD and Chi-Square tests. Results: A dose-response pattern was detected between OSDI scores and NO(2) quartiles (p < 0.05). There was a significant association between NO(2) quartiles and reported ocular irritation (X(2) = 9.2, p < 0.05) and a significant negative association between TBUT and NO(2) exposure (p < 0.05, R = -0.316. Spearman`s correlation). There was a significant increase in the frequency of meibomitis in subjects exposed to higher levels of NO(2) (p < 0.05). Conclusions: Subjects exposed to higher levels of traffic derived air pollution reported more ocular discomfort symptoms and presented greater tear film instability, suggesting that the ocular discomfort symptoms and tear breakup time could be used as convenient bioindicators of the adverse health effects of traffic derived air pollution exposure. (C) 2010 Elsevier Inc. All rights reserved.

Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy

Objective-To compare analgesic effects of tramadol, codeine, and ketoprofen administered alone and in combination and their effects on concentrations of blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing maxillectomy or mandibulectomy. Animals-42 dogs with oral neoplasms. Procedures-30 minutes before the end of surgery, dogs received SC injections of tramadol (2 mg/kg), codeine (2 mg/kg), ketoprofen (2 mg/kg), tramadol + ketoprofen, or codeine + ketoprofen (at the aforementioned dosages). Physiologic variables, analgesia, and sedation were measured before (baseline) and 1, 2, 3, 4, 5, and 24 hours after surgery. Blood glucose, serum cortisol, and serum IL-6 concentrations were measured 1, 3, 5, and 24 hours after administration of analgesics. Results-All treatments provided adequate postoperative analgesia. Significant increases in mean +/- SD blood glucose concentrations were detected in dogs receiving tramadol (96 +/- 14 mg/dL), codeine (120 +/- 66 mg/dL and 96 +/- 21 mg/dL), ketoprofen (105 +/- 22 mg/dL), and codeine + ketoprofen (104 +/- 16 mg/dL) at 5, 1 and 3, 5, and 3 hours after analgesic administration, respectively, compared with preoperative (baseline) values. There were no significant changes in physiologic variables, serum IL-6 concentrations, or serum cortisol concentrations. Dogs administered codeine + ketoprofen had light but significant sedation at 4, 5, and 24 hours. Conclusions and Clinical Relevance-Opioids alone or in combination with an NSAID promoted analgesia without adverse effects during the 24-hour postoperative period in dogs undergoing maxillectomy or mandibulectomy for removal of oral neoplasms. (Am J Vet Res 2010;71:1019-1026)

Patient based method of assessing adverse events in clinical trials in rheumatology: the revised Stanford Toxicity Index

We describe the progress towards developing a patient rated toxicity index that meets all of the patient-important attributes defined by the OMERACT Drug Safety Working Party, These attributes are frequency, severity. importance to patient, importance to the clinician, impact on economics, impact on activities, and integration of adverse effects with benefits. The Stanford Toxicity Index (STI) has been revised to collect all attributes with the exception of impact on activities. However, since the STI is a part of the Health Assessment Questionnaire (HAQ). impact on activities is collected by the HAQ. In particular, a new question asks patients to rate overall satisfaction, taking into consideration both benefits and adverse effects. The nest step in the development of this tool is to ensure that the STI meets the OMERACT filter of truth, discrimination, and feasibility. Although truth and feasibility have been confirmed by comparisons within the ARAMIS database, discrimination needs to be assessed in clinical trials.

Recoverable reserves and support effects when optimizing open pit mine designs

Orebody modelling, support effects and the estimation of recoverable reserves are key parts of open pit optimization studies. A case study is presented on the estimation of recoverable reserves using an implementation of indicator kriging where metal quantity is used to select cutoffs, and support corrections founded on a conditional simulation approach. Mining selectivity is explored in the subsequent optimization study to compare results from indicator kriging of grade estimates on a regular size blocks and indicator kriging estimates on small size blocks. The use of indicator kriging models adjusted for a given selectivity and the use of grade proportions in each block for the optimization study, provide a presentation of the expected ore recovery for a predefined level of selectivity. The case study shows that indicator kriging estimation with full accounting of block grade distributions generates substantially better results in the pit optimization study. In addition, the adverse effects of small blocks and over-smoothing on optimization results are illustrated.

A comparison of the effects of propofol and thiopental on tear production in dogs

The tear film plays an important role in maintaining the integrity of the ocular suface. During general anesthesia, tear production is considerably reduced, which requires care to prevent adverse effects that result in diseases of these structures. Studies comparing the effects of induction of anaesthesia with thiopental and propofol on tear production have not been carried out yet. Because these drugs are used in veterinary medicine, we decided to evaluate the tear production in 30 dogs undergoing experimental surgery as well as routine procedures at the veterinary hospital of Federal University of Viçosa. Patients were divided into two groups of equal number. All animals were sedated with clorpromazine and maintained with isoflurane in diluted oxygen. Group 1 was induced with thiopental whereas group 2 with propofol. Schirmer tear test 1 was performed before sedation (T0), 15 minutes after sedation (T1) and 10 minutes after induction of anesthesia (T2) with the drug chosen for one of the groups. There was a significant decrease in tear production for both drugs, but no significant statistical differences were found between them. Thus, considering the results and the way in which the study was conducted, we suggest protecting the cornea and conjunctiva of patients during anesthesia using any of the drugs here evaluated.

Air pollution effects on myocardial infarction

OBJECTIVE: Myocardial infarction is an acute and severe cardiovascular disease that generally leads to patient admissions to intensive care units and few cases are initially admitted to infirmaries. The objective of the study was to assess whether estimates of air pollution effects on myocardial infarction morbidity are modified by the source of health information. METHODS: The study was carried out in hospitals of the Brazilian Health System in the city of São Paulo, Southern Brazil. A time series study (1998-1999) was performed using two outcomes: infarction admissions to infirmaries and to intensive care units, both for people older than 64 years of age. Generalized linear models controlling for seasonality (long and short-term trends) and weather were used. The eight-day cumulative effects of air pollutants were assessed using third degree polynomial distributed lag models. RESULTS: Almost 70% of daily hospital admissions due to myocardial infarction were to infirmaries. Despite that, the effects of air pollutants on infarction were higher for intensive care units admissions. All pollutants were positively associated with the study outcomes but SO2 presented the strongest statistically significant association. An interquartile range increase on SO2 concentration was associated with increases of 13% (95% CI: 6-19) and 8% (95% CI: 2-13) of intensive care units and infirmary infarction admissions, respectively. CONCLUSIONS: It may be assumed there is a misclassification of myocardial infarction admissions to infirmaries leading to overestimation. Also, despite the absolute number of events, admissions to intensive care units data provides a more adequate estimate of the magnitude of air pollution effects on infarction admissions.

The effects of air pollution on cardiovascular diseases: lag structures

OBJECTIVE: To assess the lag structure between air pollution exposure and elderly cardiovascular diseases hospital admissions, by gender. METHODS: Health data of people aged 64 years or older was stratified by gender in São Paulo city, Southeastern Brazil, from 1996 to 2001. Daily levels of air pollutants (CO, PM10, O3, NO2, and SO2) , minimum temperature, and relative humidity were also analyzed. It were fitted generalized additive Poisson regressions and used constrained distributed lag models adjusted for long time trend, weekdays, weather and holidays to assess the lagged effects of air pollutants on hospital admissions up to 20 days after exposure. RESULTS: Interquartile range increases in PM10 (26.21 mug/m³) and SO2 (10.73 mug/m³) were associated with 3.17% (95% CI: 2.09-4.25) increase in congestive heart failure and 0.89% (95% CI: 0.18-1.61) increase in total cardiovascular diseases at lag 0, respectively. Effects were higher among female group for most of the analyzed outcomes. Effects of air pollutants for different outcomes and gender groups were predominately acute and some "harvesting" were found. CONLUSIONS: The results show that cardiovascular diseases in São Paulo are strongly affected by air pollution.

Isolated and synergistic effects of PM10 and average temperature on cardiovascular and respiratory mortality

OBJECTIVE To analyze the effect of air pollution and temperature on mortality due to cardiovascular and respiratory diseases. METHODS We evaluated the isolated and synergistic effects of temperature and particulate matter with aerodynamic diameter < 10 &#181;m (PM10) on the mortality of individuals > 40 years old due to cardiovascular disease and that of individuals > 60 years old due to respiratory diseases in Sao Paulo, SP, Southeastern Brazil, between 1998 and 2008. Three methodologies were used to evaluate the isolated association: time-series analysis using Poisson regression model, bidirectional case-crossover analysis matched by period, and case-crossover analysis matched by the confounding factor, i.e., average temperature or pollutant concentration. The graphical representation of the response surface, generated by the interaction term between these factors added to the Poisson regression model, was interpreted to evaluate the synergistic effect of the risk factors. RESULTS No differences were observed between the results of the case-crossover and time-series analyses. The percentage change in the relative risk of cardiovascular and respiratory mortality was 0.85% (0.45;1.25) and 1.60% (0.74;2.46), respectively, due to an increase of 10 &#956;g/m3 in the PM10 concentration. The pattern of correlation of the temperature with cardiovascular mortality was U-shaped and that with respiratory mortality was J-shaped, indicating an increased relative risk at high temperatures. The values for the interaction term indicated a higher relative risk for cardiovascular and respiratory mortalities at low temperatures and high temperatures, respectively, when the pollution levels reached approximately 60 &#956;g/m3. CONCLUSIONS The positive association standardized in the Poisson regression model for pollutant concentration is not confounded by temperature, and the effect of temperature is not confounded by the pollutant levels in the time-series analysis. The simultaneous exposure to different levels of environmental factors can create synergistic effects that are as disturbing as those caused by extreme concentrations.

Effects of acupressure on progress of labor and cesarean section rate: randomized clinical trial

OBJECTIVE To analyze the effects of acupressure at the SP6 point on labor duration and cesarean section rates in parturients served in a public maternity hospital.METHODS This controlled, randomized, double-blind, pragmatic clinical trial involved 156 participants with gestational age &#8805; 37 weeks, cervical dilation &#8805; 4 cm, and &#8805; 2 contractions in 10 min. The women were randomly divided into an acupressure, placebo, or control group at a university hospital in an inland city in the state of Sao Paulo, Brazil, in 2013. Acupressure was applied to the SP6 point during contractions for 20 min.RESULTS The average labor duration was significantly different between the SP6 acupressure group [221.5 min (SD = 162.4)] versus placebo [397.9 min (SD = 265.6)] and versus control [381.9 min (SD = 358.3)] (p = 0.0047); however, the groups were similar regarding the cesarean section rates (p = 0.2526) and Apgar scores in the first minute (p = 0.9542) and the fifth minute (p = 0.7218) of life of the neonate.CONCLUSIONS The SP6 acupressure point proved to be a complementary measure to induce labor and may shorten the labor duration without causing adverse effects to the mother or the newborn. However, it did not affect the cesarean section rate.

Characterization of the Toxicological Effects of Aminocarb on Rats: Hematological, Biochemical, and Histological Analyses

Aminocarb is a widely applied carbamate insecticide with action of controlling pests such as Lepidoptera and Coleoptera. In this study, subchronic effects on Wistar rats were investigated using hematological, biochemical, and histological techniques. Rats were exposed orally at sublethal levels of 10, 20, or 40 mg/kg body weight (groups A, B, and C, respectively) for 14 d. Hematological results revealed no statistical differences after 1 d of exposure but significant reduction in white blood cells detected after 7 d of exposure in group C, as well as, in all treated groups after 14 d of exposure. Biochemical data showed a decrease of acetylcholinesterase activity in all groups after 1 d of exposure with a return to normal after 7 and 14 d. Significant increase in alkaline phosphatase activity of rats exposed to aminocarb was noted after 7 d of treatment. The levels of triglycerides were also significantly decreased. The present investigation also showed a significant increase in content of serum urea and creatinine in animals from group A (14 d), and from groups B and C (7 and 14 d). Histological results demonstrated hemorrhagic focus on hepatic and renal parenchyma in all exposed groups. Taken together, the attained results were dose dependent and indicated adverse effects of aminocarb on hepatic and renal functions, as well as on immune responsiveness at sublethal tested doses.

ADVERSE EFFECT VERSUS QUALITY CONTROL OF THE FUENZALIDA-PALACIOS ANTIRABIES VACCINE

We evaluated the components of the Fuenzalida-Palacios antirabies vaccine, which is till used in most developing countries in human immunization for treatment and prophylaxis. This vaccine is prepared from newborn mouse brains at 1% concentration. Even though the vaccine is considered to have a low myelin content, it is not fully free of myelin or of other undesirable components that might trigger adverse effects after vaccination. The most severe effect is a post-vaccination neuroparalytic accident associated with Guillain-Barré syndrome. In the present study we demonstrate how the vaccines produced and distributed by different laboratories show different component patterns with different degrees of impurity and with varying protein concentrations, indicating that production processes can vary from one laboratory to another. These differences, which could be resolved using a better quality control process, may affect and impair immunization, with consequent risks and adverse effects after vaccination. We used crossed immunoelectrophoresis to evaluate and demonstrate the possibility of quality control in vaccine production, reducing the risk factors possibly involved in these immunizing products.

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.

Comparative effects of sediments contaminated by carcinogenic and non-carcinogenic PAHs in Dicentrarchus labrax: a semi-quantitative histopathological approach

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente