Perioperative administration of vedaprofen, tramadol or their combination does not interfere with platelet aggregation, bleeding time and biochemical variables in cats

A randomized double blind and placebo controlled design was used to investigate the hemostatic, biochemical, gastrointestinal and behavioral effects of pre- and postoperative administration of vedaprofen 0.5 mg/kg PO (V), tramadol 2 mg/kg SC (T), their association (VT) or placebo (P) in 40 adult female cats (3.0 +/- 0.32 kg; 1.8 +/- 0.7 years) distributed in groups of 10. Platelet aggregation and bleeding time were measured before and 52 11 after ovariohysterectomy. Serum urea, creatinine, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transferase concentrations were measured before and 7 days postoperatively. The occurrence of vomiting, frequency and consistency of feces, and behavior were observed for 7 days postoperatively. Morphine (0.5 mg/kg, IM) was used as rescue analgesic. Laboratory variables did not change. Vomiting was observed only after morphine administration. Mild euphoria was observed in T and VT. The perioperative use of vedaprofen and/or tramadol did not modify the hemostatic, biochemical and gastrointestinal function in cats. (C) 2009 ESFM and AAFP. published by Elsevier Ltd. All rights reserved.

Long-Term Outcome and Prognostic Factors of Juvenile Dermatomyositis: A Multinational, Multicenter Study of 490 Patients

Objective. To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study.Methods. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL).Results. A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%.Conclusion. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine

The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

Long-term toxicity following acute administration of nickel

Nickel compounds have high potential risk for the health of populations and for this reason their toxic effects should be urgently established. To determine the effect of nickel monosulfide in the muscle at the injection site on pancreatic, hepatic, and osteogenic lesions and the potential therapeutic effect of Cu-Zn superoxide dismutase (SOD), male Wistar rats received single intramuscular injections of nickel monosulfide (NiS - 7 mg Ni2+/Kg). A group of these experimental rats were injected intraperitoneally, with a single weekly dose of SOD covalently linked to polyethylene glycol (SOD-PEG). Rats were sacrificed at 2, 4, 6, and 8 months after Ni2+ injection. Nickel monosulfide produced tumors at the injection site. The increased phospholipid, alanine transaminase (ALT), alkaline phosphatase (ALP), and amylase levels in serum, in absence of SOD-PEG, reflected the toxic effects on pancreatic, hepatic, and osteogenic tissues of rats. SOD activity was increased in serum of rats receiving SOD-PEG throughout the experiment, and no significant difference was observed in biochemical parameters of control and experimental rats in presence of SOD- PEG. Superoxide radical generated by Ni2+ is of primary importance in the development of tumors at the injection site. Superoxide anion (O2 -) is also an important toxic intermediate with respect to hepatic, pancreatic, and osteogenic injury, since SOD-PEG has a potential therapeutic effect.

Experimental control of the effect of extra doses of juvenile hormone on bee development: The case of the wax glands of Apis mellifera (Hymenoptera: Apidae)

Experiments on the effect of topical application of the synthetic juvenile hormone (JH-III) and of the solvent used to dissolve the hormone on the development of the wax glands of workers of Apis mellifera, were made. The results show that it was impossible to determine the effect of the juvenile hormone (JH) apart from its solvent (acetone), which also alters the developmental pattern of the gland. Most of the experiments reported in scientific literature do not consider the effect of the solvent, analyzing the results by only comparing the treatment with the hormone plus solvent to a control without any treatment. The data presented suggests that this kind of procedure compromises the evaluation of the real JH effect.

Effect of fish density during transportation on stress and mortality of juvenile Tambaqui Colossoma macropomum

The increased demand for juvenile tambaqui Colossoma macropomum for grow-out ponds and stocking programs in the Amazon state of Brazil has increased the transportation of this species. This study was designed to determine the optimum density of juvenile tambaqui during transportation in closed containers. Fish (51.9 ± 3.3 g and 14.9 ± 0.4 cm) were packed in sealed plastic bags and transported for 10 h at four densities: 78, 156, 234, and 312 kg/m3. After transportation, fish from each density were kept in separate 500-L tanks for 96 h. Mortality, 96-h cumulative mortality, water quality, and blood parameters (hematocrit, plasma cortisol, and glucose) were monitored. Fish mortality after transportation was significantly lower at densities of 78 and 156 kg/m3 than at 234 and 312 kg/m3. Cumulative mortality was significantly lower at a density of 78 kg/m3. Dissolved oxygen after 10 h of transportation remained high at a density of 78 kg/m3, but reached critically low values at all other densities. Ammonia concentration was highest at the lowest density and was lower at higher densities. Carbon dioxide concentration was lowest at the density of 78 kg/m3 but higher in the other treatments. Plasma glucose and cortisol increased significantly immediately after transportation at densities of 156, 234, and 312 kg/m3, returning to control values by 24 h. The best density for juvenile tambaqui during a 10-h transportation haul in a closed container was 78 kg/m3. At this density there was no fish mortality, water quality was kept within acceptable values, and fish were not stressed.

Influence of the application of juvenile hormone on the haemolymph total proteins and electrophoretic pattern of worker larvae of Apis mellifera

The aim of the present work was to verify the influence of the juvenile hormone (JH) applied on worker larvae of Apis mellifera 2 to 5 days old over the haemolymph total protein and electrophoretic pattern. Each larvae received topical applications of 1 ml of a solution of JH in hexane (1 μg/ml) on their 2 nd, 3 rd 4 th and 5 th day after hatching and had the amount and electrophoretic pattern of proteins from the haemolymph analyzed during the remaining days of their life. As a control, haemolymph of larvae of the same age that did not receive any kind of treatment was analyzed. The results show that the application of JH on larvae 3 or more days old affect the amount and electrophoretic pattern of the proteins, with this effect lasting through the subsequent days.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Neurohormonal, hemodynamic, and electrocardiographic evaluations of healthy dogs receiving long-term administration of doxorubicin

Objective - To evaluate diagnostic testing that could be used to establish an early diagnosis of cardiotoxicosis induced by long-term administration of doxorubicin. Animals - 13 adult mixed-breed dogs. Procedures - 7 dogs were administered doxorubicin chloride (30 mg/m2, IV, q 21 d for 168 days [cumulative dose, 240 mg/m2]), and 6 dogs received saline (0.9% NaCl) solution (5 mL, IV, q 21 d for 168 days; control group). Echocardiography, ECG, arterial blood pressure, plasma renin activity (PRA), and plasma concentrations of norepinephrine and brain natriuretic peptide (BNP) were assessed before each subsequent administration of doxorubicin and saline solution. Results - Dogs that received doxorubicin had a significant decrease in R-wave amplitude, compared with values for the control group, from 30 to 210 mg/m2. Doxorubicin-treated dogs had decreases in fractional shortening and left ventricular ejection fraction evident as early as 30 mg/m2, but significant differences between groups were not detected until 90 mg/m2 was reached. There was also a significant increase in PRA (≥ 120 mg/m2) and left ventricular end-systolic and end-diastolic dimensions (≥ 60 and ≥ 180 mg/m2, respectively). Systemic arterial pressure, remaining echocardiographic variables, and concentrations of norepinephrine and BNP had significant variations, but of no clinical importance, during doxorubicin administration. Conclusions and clinical relevance - Doxorubicin-induced cardiotoxicosis developed at 120 mg/m2, but there were no clinical signs of dilated cardiomyopathy or congestive heart failure. Echocardiography and determination of PRA were able to detect early cardiac alterations during the development of dilated cardiomyopathy, despite apparently differing degrees of sensitivity to development of doxorubicin-induced cardiotoxicosis.

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

Objective - To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Animals - 36 adult dogs. Procedures - Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. Results - For serum γ-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Conclusions and Clinical Relevance - Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Serum protein profiles of juvenile ring-necked pheasants vaccinated or not against newcastle disease

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

Chronic administration of risperidone in a rat model of schizophrenia: A behavioural, morphological and molecular study

In the present work we analyzed the effect of the chronic administration of risperidone (2mg/kg over 65 days) on behavioural, morphological and molecular aspects in an experimental model of schizophrenia obtained by bilateral injection of ibotenic acid into the ventral hippocampus of new-born rats. Our results show that during their adult lives the animals with hippocampal lesions exhibit different alterations, mainly at behavioural level and in the gene expression of dopamine D2 and 5-HT2A receptors. However, at morphological level the study performed on the prefrontal cortex did not reveal any alterations in either the thickness or the number of cells immunoreactive for c-Fos, GFAP, CBP or PV. Overall, risperidone administration elicited a trend towards the recovery of the values previously altered by the hippocampal lesion, approaching the values seen in the animals without lesions. It may be concluded that the administration of risperidone in the schizophrenia model employed helps to improve the altered functions, with no significant negative effects. © 2013.

Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy

The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G′) at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT. For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8 mg/kg. The intranasal administration of PA resulted in a fast absorption process (Tmax = 6.7 min). Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs. In the present study, the uptake of AZT absorption in the nasal mucosa was demonstrated, providing new foundations for clinical trials in patients with AIDS. © 2012 Elsevier B.V. All rights reserved.

Morphometry and expression of MyoD and Myogenin in white and red skeletal muscles of juvenile fish Colossoma macropomum (Cuvier 1818)

Colossoma macropomum, also known as tambaqui, is an economically important fish species, and interesting new studies have been published with the aim of improving the growth of this fish. In this work, we describe the morphometric characteristics, as well as the mRNA and protein expression levels of two myogenic regulatory factors (MRFs)-myod/MyoD and myogenin/Myogenin-in the white and red muscle types of tambaqui. A high proportion of white and red muscle fibers with large diameters suggest a hypertrophic growth process in the skeletal muscle during juvenile stages. Comparisons between muscle types showed that, in red muscle, myogenin transcript levels were significantly higher than those of myod. In contrast, MyoD protein levels were significantly higher than those of Myogenin in red muscle. These results suggest that in red and white muscles of juvenile tambaqui, independent post-transcriptional mechanisms for regulating MyoD and Myogenin expression may exist, which could be differentially activated during muscle growth. Furthermore, these data also suggest that specific control mechanisms may regulate distinct muscle phenotypes. © 2013 The Royal Swedish Academy of Sciences.