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.

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. (J Toxicol Pathol 2010; 23: 171-181)

Segurança clínica e eficácia terapêutica de uma nova formulação ectoparasiticida em bovinos natural e experimentalmente infestados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Atividade endectocida, segurança clínica e farmacocinética de resíduos de uma nova alternativa terapêutica (Fluazuron + Abamectina) em bovinos

Pós-graduação em Medicina Veterinária - FCAV

Effectiveness and safety of endotracheal tube cuffs filled with air versus filled with alkalinized lidocaine: a randomized clinical trial

CONTEXTO E OBJETIVO: Os tubos traqueais são dispositivos utilizados para manutenção da ventilação. A hiperinsuflação do balonete do tubo traqueal, causada pela difusão do óxido nitroso (N2O), pode determinar lesões traqueais, que se manifestam clinicamente como odinofagia, rouquidão e tosse. A lidocaína, quando injetada no balonete do tubo traqueal, difunde-se através de sua parede, determinando ação anestésica local na traquéia. O objetivo foi avaliar a efetividade e a segurança do balonete do tubo traqueal preenchido com ar comparado com o balonete preenchido com lidocaína, considerando os desfechos: sintomas cardiovasculatórios (HAS, taquicardia); odinofagia, tosse, rouquidão e tolerância ao tubo traqueal. TIPO DE ESTUDO E LOCAL: Estudo clínico prospectivo, realizado no Departamento de Anestesiologia da Faculdade de Medicina da Unesp, campus de Botucatu. MÉTODOS: A pressão do balonete do tubo traqueal foi medida, entre 50 pacientes, antes, 30, 60, 90 e 120 minutos após o início da inalação de N2O anestésico. As pacientes foram distribuídas aleatoriamente em dois grupos: Air, em que o balonete foi inflado com ar para obtenção de pressão de 20 cm H2O, e Lido, em que o balonete foi preenchido com lidocaína a 2% mais bicarbonato de sódio a 8,4% para obtenção da mesma pressão. O desconforto antes da extubação, e manifestações clínicas como dor de garganta, rouquidão e tosse foram registrados no momento da alta da unidade de cuidados pós-anestésicos, e dor de garganta e rouquidão foram avaliadas também 24 horas após a anestesia. RESULTADOS: Os valores da pressão no balonete em G2 foram significativamente menores do que os de Air em todos os tempos de estudo, a partir de 30 minutos (p < 0,001). A proporção de pacientes que reagiu ao tubo traqueal no momento da desintubação foi significantemente menor em Lido (p < 0,005). A incidência de odinofagia foi significantemente menor em Lido no primeiro dia de pós-operatório (p < 0,05). A incidência de tosse e rouquidão não diferiu entre os grupos. CONCLUSÕES: Durante ventilação artificial, empregando-se a mistura de oxigênio e N2O, a insuflação do balonete com lidocaína 2% alcalinizada impede que ocorra aumento significante da pressão no balonete e determina maior tolerância ao tubo traqueal e menor incidência de odinofagia no pós-operatório, podendo então ser considerada mais segura e com maior efetividade.

Pharmacokinetic and safety evaluation of the use of ciprofloxacin on an isoniazid-rifampicin regimen in rabbits

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

Improved laboratory safety by decontamination of unstained sputum smears for acid-fast microscopy

Tubercle bacilli may survive in unstained heat-fixed sputum smears and may be an infection risk to laboratory staff. We compared the effectiveness of 1% and 5% sodium hypochlorite, 5% phenol, 2% glutaraldehyde, and 3.7% formalin in killing Mycobacterium tuberculosis present in smears prepared from 51 sputum samples. The smears were decontaminated by the tube and slide techniques. Phenol at 5%, glutaraldehyde at 2%, and buffered formalin at 3.7% for 1 min (tube technique) or for 10 min (slide technique) were effective in decontaminating sputum smears and preserved cell morphology and quantitative acid-fast microscopy results.

Safety Assessment of Potentially Inappropriate Medications (PIM) use in Older People and the Factors Associated with Hospital Admission

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

Objective. We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study.Methods. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >= 21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008.Results. of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.Conclusion. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Studies of gastric mucosa regeneration and safety promoted by Mouriri pusa treatment in acetic acid ulcer model

Ethnopharmacological Relevance: Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used by people living in the Cerrado to treat gastrointestinal disturbances. This medicinal plant has shown intense gastroprotective action in rodent gastric lesion, but still there are no data about its healing effect on gastric mucosa.Aim of the Study: To evaluate the methanolic extract (MeOH) obtained from Mouriri pusa leaves for its effect on the cicatrisation process of gastric ulcer.Mterials and Methods: The healing effects on gastric ulcers inducted by subserosal injection of acetic acid were evaluated by macroscopic and microscopic measures, imunohistochemistry and cell counting in rats treated with MeOH extract of Mouriri pusa (250 mg/kg, p.o./daily) for 14 or 30 days. The toxicity of Mouriri pusa was also evaluated by body and organ weight measure and clinical biochemical parameters.Results: Mouriri pusa treatments lasting 14 and 30 days showed elevated mucus secretion (PAS) and thicker regenerative gastric mucosa, denoting increased cell proliferation, which was confirmed by PCNA immunohistochemical analysis. Moreover, there was important cell recruitment (neutrophils and mast cells) to the site of the ulcer, which is an important factor in ulcer healing. No toxic effect was observed in all parameters evaluated. Phenolic compounds present in the MeOH extract like tannins, flavonoids and epicatechin are the probable agents involved in the healing effects of this medicinal plant.Conclusions: These findings showed a potential effect of Mouriri pusa in increasing regeneration of damaged gastric mucosa with safety for human use. (C) 2007 Elsevier B.V. All rights reserved.

Effectiveness and safety of a new vaginal misoprostol product specifically labeled for cervical ripening and labor induction

Objective. The purpose of this study was to evaluate the effectiveness and safety of misoprostol in two different formulations: vaginal tablets of 25 mu g and one-eighth of a 200-mu g oral tablet, also administered intravaginally, for cervical ripening and labor induction of term pregnancies with an indication for that. Methods. A single-blind, randomized, controlled clinical trial was carried out in 120 pregnant women who randomly received one of the two formulations. The main dependent variables were mode of delivery, need for additional oxytocin, time between beginning of induction and delivery, perinatal results, complications, and maternal side effects. Student's t, Mann-Whitney, chi(2), Fisher's Exact, Wilcoxon and Kolmogorov-Smirnoff tests, as well as survival analysis, were used in the data analysis. Results. There were no significant differences between the groups in terms of general characteristics, uterine contractility, and fetal well-being during labor, cesarean section rates, perinatal outcomes, or maternal adverse events. The mean time between the beginning of cervical ripening and delivery was 31.3 h in the vaginal tablet group and 30.1 h in the oral tablet group, a difference that was not statistically significant. Conclusion. The results showed that the 25-mu g vaginal tablets of misoprostol were as effective and safe for cervical ripening and labor induction as the dose-equivalent fraction of 200-mu g oral tablets.

Phase II clinical study of an association for the treatment of interstitial cystitis (Cystex (R))

Painful bladder syndrome associated with interstitial cystitis (PBS/IC) is a clinical condition characterized pelvic pain, urinary urgency, and urinary frequency. In this study, 22 patients were assigned to make two visits over a three weeks period. The patients were randomly, double-blinded assigned in two groups. The first group received Cystex (R) capsules. The second group received placebo capsules. Two capsules were taken three times a day away from meals. The change from baseline in the O'Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and intensity of pain and urgency have been chosen as secondary outcome parameters. Mood as well as physical and sexual activity were rated by 10 questions on a scale 0 to 6. The ratings were analyzed and the average for each patient in both groups Cystex (R) and placebo was determined as the quality of life index. For the primary outcome there was a statistically significant difference between the groups. Mean symptom score-sum decreased from 28.4 to 20.5 in the Cystex (R) group compared with 29.5 to 26.8 in the placebo group (p<0.05). For the secondary end points, pain and urgency intensity improved statistically significantly in the Cystex (R) group compared with the placebo group (p<0.05). The frequency and functional bladder capacity improved to greater degree in the Cystex (R) group. The differences were statistically significant for comparison of frequency (p<0.05) and not for functional bladder capacity (p>0.05). In our study, Cystex (R) enhanced quality of life over the placebo showing a statistically significant. This trial have shown that the efficacy and safety of therapy with Cystex (R) in the treatment of interstitial cystitis and is an alternative for patients suffering from this pathology. Therefore, it can be concluded that the composition of Cystex (R), increased the quality of life in treated patients.

Efficacy, safety and tolerability of terbinafine for Tinea capitis in children: Brazilian multicentric study with daily oral tablets for 1, 2 and 4 weeks

Background: Tinea capitis is a common skin disease seen predominantly in children. The standard therapies for this disease are griseofulvin and ketoconazole. Nevertheless, these drugs have drawbacks in that they are only fungistatic and require treatment for at least 6 weeks. Previous studies with oral terbinafine for the treatment of Tinea capitis have shown that this agent is effective when given for 4 weeks, comparable to an 8-week regimen with griseofulvin. To date there is no data on the use of oral terbinafine in Brazilian children. Objectives: To assess the efficacy, safety and tolerability of oral terbinafine in short-term treatments (1-, 2- and 4-week treatment) of Tinea capitis in children. Patients and methods: One hundred and thirty-two children aged 1-14 years were enrolled in this study, but only 107 were considered for the final efficacy analysis. Diagnosis included clinical assessment and examination by Wood's light. Confirmation was obtained by direct microscopy and culture for fungus. Terbinafine dosage (125 or 250 mg/day) was adjusted according to patient weight. Efficacy was evaluated both by clinical and mycological assessment. Safety and tolerability variables included data on adverse reaction and clinical laboratory evaluations. Results: Mycological evaluation in the follow-up visit at week 12 showed negative direct microscopy and culture results in 48.6, 60.5 and 69.7% patients in groups 1-, 2- and 4-week, respectively (n.s.). At week 12, 84.8% patients in group 4-week achieved clinical cure with a significant difference compared to groups 1- and 2-week, 54.3 and 60.5%, respectively (P < 0.01). Adverse reactions were present in 4.8, 6.8 and 10.9% of patients in groups 1-, 2- and 4-week, respectively. Terbinafine was not associated with clinically relevant increases in liver function tests. Conclusions: Terbinafine is an effective, well tolerated and safe antifungal agent for the treatment of Tinea capitis m children. The shorter duration of treatment resulted in lower cure rates. However, it is important to note that depending on the severity of the disease, a 1-week-only treatment can also be effective in this indication.

Acute coronary syndrome associated with continuous 5-fluorouracil infusion in a patient with metastatic colorectal cancer-a case report with a discussion on this clinical dilemma

Introduction: 5-Fluorouracil (5-FU) is considered to be the backbone of colorectal cancer (CRC) systemic therapy since the great majority of recommended regimens include its administration. A clinical picture consisting of chest pain, sometimes cardiac enzyme elevation, electrocardiogram abnormalities consistent with myocardial ischemia, and normal coronary angiogram associated with 5-FU administration have been infrequently reported. The clinical dilemma is: Which chemotherapy regimen should we use in CRC patients with a previous acute coronary syndrome (ACS) associated with 5-FU? Case Report: We describe the case of a 55-year-old otherwise healthy woman with metastatic colon adenocarcinoma who presented an ACS probably secondary to arterial vasospasm while receiving continuous intravenous 5-FU infusion (mFOLFOX6 regimen). After the ACS, the patient was treated with raltitrexate plus oxaliplatin (TOMOX) and subsequently with irinotecan plus cetuximab with no other cardiac event. Conclusion: The risk of cardiotoxicity associated with 5-FU is low but real. The probable mechanism is arterial vasospasm, as suggested by our case report. Both the use of the TOMOX regimen and irinotecan plus cetuximab seems to be safe regimens to be considered in this clinical scenario. © 2009 Humana Press Inc.