Safety assessment of oral photodynamic therapy in rats

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

Evaluation of clinical safety and anthelmintic efficacy of aurixazole administed orally at 24 mg/kg in cattle

The current study evaluated, in vivo, the clinical safety and the anthelmintic efficacy of 24% aurixazole (24 mg/kg), administered orally, in bovines. Two experiments were conducted: the first one evaluating the clinical safety of 24% aurixazole (24 mg/kg) in cattle, and a second one evaluating the anthelmintic efficacy of aurixazole (24 mg/kg) against gastrointestinal nematodes on naturally infected cattle. Based on the results of clinical safety, no alterations on clinical and haematological signs and on the biochemical values obtained in animals treated orally with aurixazole 24 mg/kg were observed. Regarding the results of reduction or efficacy, obtained by eggs per gram of faeces (EPG) counts, the formulation of aurixazole reached values superior to 99% (arithmetic means) in all post-treatment dates. In two occasions, this formulation reached maximum efficacy (100%). Comparing these results with the reduction percentages obtained by EPG counts, it is possible to verify that the values obtained by all three formulations were compatible with the efficacy results. Aurixazole reached maximum efficacy (100%) against Haemonchus placei, Cooperia spatulata and Oesophagostomum radiatum. Against Cooperia punctata, this formulation reached an efficacy index of 99.99%. Regarding aurixazole, no specific trials were conducted on the field in order to evaluate the behaviour of this molecule against helminths that are resistant to other molecules, specially isolated levamisole and disophenolat: Due to this fact, future studies will be necessary to assess the effectiveness of aurixazole against strains of nematodes that are resistant to levamisole and disophenolat, but the results of clinical safety and efficacy described in this study allow us to conclude that the aurixazole molecule, concomitantly with other measures and orally administered formulations, can be another important tool in the control of nematodes parasitizing bovines. (C) 2014 Published by Elsevier Ltd.

Fatigue Behavior of Weld Repaired AISI 4130 Aeronautic Steel Used in Critical Flight Safety Structures

Since the 1950s, fatigue is the most important project and operational consideration for both civil and military aircrafts. For some aircraft models the most loaded component is one that supports the motor: the Motor Cradle. Because they are considered critical to the flight safety the aeronautic standards are extremely rigorous in manufacturing them by imposing a zero index of defects on the final weld quality (Safe Life), which is 100% inspected by Non-Destructive Testing/NDT. This study has as objective to evaluate the effects of up to four successive TIG welding repairs on the axial fatigue strength of an AISI 4130 steel. Tests were conducted on hot-rolled steel plate specimens, 0.89 mm thick, with load ratio R = 0.1, constant amplitude, at 20 Hz frequency and in room temperature, in accordance with ASTM E466 Standard. The results were related to microhardness and microstructural and geometric changes resulting from welding cycles.

Child safety from the perspective of essential needs

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

Safety performance models for urban intersections in Brazil

This paper presents a modeling effort for developing safety performance models (SPM) for urban intersections for three major Brazilian cities. The proposed methodology for calibrating SPM has been divided into the following steps: defining the safety study objective, choosing predictive variables and sample size, data acquisition, defining model expression and model parameters and model evaluation. Among the predictive variables explored in the calibration phase were exposure variables (AADT), number of lanes, number of approaches and central median status. SPMs were obtained for three cities: Fortaleza, Belo Horizonte and Brasilia. The SPM developed for signalized intersections in Fortaleza and Belo Horizonte had the same structure and the most significant independent variables, which were AADT entering the intersection and number of lanes, and in addition, the coefficient of the best models were in the same range of values. For Brasilia, because of the sample size, the signalized and unsignalized intersections were grouped, and the AADT was split in minor and major approaches, which were the most significant variables. This paper also evaluated SPM transferability to other jurisdiction. The SPM for signalized intersections from Fortaleza and Belo Horizonte have been recalibrated (in terms of the COx) to the city of Porto Alegre. The models were adjusted following the Highway Safety Manual (HSM) calibration procedure and yielded C-x of 0.65 and 2.06 for Fortaleza and Belo Horizonte SPM respectively. This paper showed the experience and future challenges toward the initiatives on development of SPMs in Brazil, that can serve as a guide for other countries that are in the same stage in this subject. (C) 2014 Elsevier Ltd. All rights reserved.

Use of HEPG2 cells to assay the safety of cosmetic active substances

The importance of this study is based on the need to obtain simple and efficient in vitro models to predict the in vivo toxicity of cosmetics, aiming not to use animals as experimental model. Here, we proposed the use of HepG2 cells, which are widely applied to simulate the hepatic function of the human organism in vitro. This cell line was chose since recent studies have shown that the liver is potentially the most frequently targeted organ by cosmetic ingredients, and beyond that, considering the widely application of in vitro assays to test the cutaneous permeation of cosmetic products, including the assays applying modified Franz cells, this technique becomes indispensable. Three different cosmetic active substances were used, and the toxicity to HepG2 cells was assessed by the MTT method. The treatment with hyaluronic acid showed no toxicity to HepG2 cells. Treating the cells with P. guajava L. extract were verified that increasing the amount of the extract in the media, the cellular viability decreased, and finally, the treatment of alpha-lipoic acid showed a cytoprotective effect in relation to the treatment with propylene glycol. The study demonstrated the suitability in using HepG2 cells to assess the safety of cosmetic active substances, helping in the prediction of if the substance could be hepatotoxic if could reach the bloodstream

Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses

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

Safety of kidney transplantation using anti-HBc-positive donors

Background. Prospective studies evaluating the risk of hepatitis B virus (HBV) transmission in transplants of kidneys from hepatitis B core antibody (anti-HBc)-positive/ hepatitis B surface antibody (anti-HBs) negative donors are still lacking. The objective of this study was to assess the safety of kidney transplantation with the use of anti-HBc positive donors.Methods. This prospective case series study included 50 kidney transplant recipients from anti-HBc positive donors with or without anti-HBs positivity. Recipients were required to test positive for anti-HBs (titers >10 mUI/mL), regardless of anti-HBc status, and negative for hepatitis B surface antigen (HBsAg). Recipient and donor data were retrieved from medical records, databases, and organ procurement organization sheets. Liver function tests were performed at progressively increasing post-transplantation intervals. Complete serologic tests for HBV were performed before transplantation, 3 and 6 months after transplantation, and annually thereafter.Results. Six months after transplantation, all recipients were negative for HBsAg, HBeAg, anti-HBe, and anti-HBcIgM. No seroconversion was observed among the 20 patients who received kidneys from anti-HBc positive/anti-HBs negative donors. No patient showed elevated liver enzymes during follow-up.Conclusions. Kidney transplantation using organs from anti-HBeIgG positive donors (even when they are concurrently anti-HBs negative) in anti-HBs positive recipients is a safe procedure and may be considered as a way to expand the donor pool.

Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Safety assessment of essential medicines for elderly people: a bibliographic survey

Certain medicines are considered potentially inappropriate (PIM) for elderly people as they increase the risk of adverse drug events (ADE) and because safer alternative therapies are available on the market. In this context, in order to identify the instruments that assess the quality of medical prescriptions for elderly and to determine which drugs are considered PIM, a bibliographic survey was conducted in PUBMED, LILACS and PAHO databases, in February and March/2010. The search strategy included the use of health descriptors and a manual search in the references cited by selected papers. During the period of data collection, 15 instruments were identified. In 2012, with the publication of the update of Beers criteria, this instrument was included in the study. We identified 163 PIM of 25 therapeutic classes, of which 125 (76.7%) are marketed in Brazil. Of these, 31 (24.8%) are essential medicines (RENAME 2012), of which 13 have safer therapeutic equivalents and 19 (15.2%) are over-the-counter drugs. Data suggest the need for inclusion of safer alternatives for the elderly in the national list of essential medicines and the pharmaceutical care for early detection of ADE in this age group, in order to contribute to the safe use of medicines.

Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy

To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM-FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19-35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM-FC was initiated and administered once daily at 8 pm for 4-6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). A total of 49 patients were enrolled (mean age, 63 [range, 42-82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM-FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM-FC) was -5.0±3.6 mmHg. IOP decreased significantly (P<0.0001) from baseline (22.1±2.6 mmHg) to study end (17.1±3.9 mmHg) in the ITT population, with a mean IOP reduction of 22.3%. Most patients (n=33/45; 73.3%) achieved IOP ≤18 mmHg. Two patients experienced a total of four adverse events (AEs), including a patient who reported one serious AE (enterorrhagia) that was considered unrelated to treatment, and a patient who reported one event each of drug-related redness, pruritus, and foreign body sensation. Most patients (n=47/49; 95.9%) reported no AEs. TRAV/TIM-FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM-FC. TRAV/TIM-FC was well tolerated in this population.

In Vitro Safety Evaluation of Caffeic Acid

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

Improving logistics services through the technology used in fleet management

Outsourcing logistics has established itself in the area of the LSP (Logistics Service Provider), which offers a range of services to its customers. In this line, transportation is characterized as one of the most important services, and therefore efficient fleet management is essential for establishing a high level of customer service. With advances in technology and vehicle tracking systems, this approach of management has gained new possibilities for the improvement of logistics services. By studying the specific case of an LSP, this paper investigates the use of these technologies in the management of their business and services. The results indicate that the LSP seeks to increase its services and to streamline information in order to respond to customer needs in real time. It is also evident in this case under study that the combination of the technology available together with the fleet management system has become a distinguishing feature for this LSP, one which increases their skills and important information for both customers and business.

Geografia da mortalidade no trânsito no Brasil

In road safety studies that involve accidents comparisons in distinct geographical spaces or in different periods of time in the same geographical space, the index which lists the number of traffic fatalities with the distance traveled by road transport vehicles is considered more appropriate than the rates related to the population or the fleet. In this paper, the results of an original research are presented, in which the values of the rate of traffic deaths per billion kilometers traveled (IMBQ) by the motor vehicle fleet in Brazil and in each state of the country were estimated. The evaluation was performed based on the official number of fatalities provided by the Ministry of Health and on the amount of fuel sold informed by the National Agency of Petroleum, Natural Gas and Biofuels. In 2009, Brazil presented an index of 52.84 fatalities per billion kilometers, which reveals an extremely alarming situation considering that this value is from 7 to 12 times higher than the one for more developed countries. An important correlation between the death index in the states and the Gross Domestic Product (GDP) per capita was observed; in general, the less economically developed is the state, it means, lowest GDP, higher is the IMBQ.