Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.

Problems related to the employment of thin uranium films as neutron dosimeters

Thin uranium films built on muscovite mica basis and obsidian samples having known ages were irradiated with thermal neutrons at the IPEN/CNEN reactor, São Paulo. Comparing thin film performance with the obsidian one, it was observed that the latter feel a greater neutron fluence. Nominal fluences at the used facility are in agreement with the results obtained analysing the obsidian samples. A probable hypothesis to explain this disagreement, namely, the uranium loss from the thin films, was ruled out. © 1995.

Energetic cost of predation: Aerobic metabolism during prey ingestion by juvenile rattlesnakes, Crotalus durissus

We investigated the cost of prey ingestion in the South American rattlesnake, Crotalus durissus, to see if the capacity to generate energy aerobically could be a constraint on the size of the prey that can be ingested. To accomplish this goal, we measured time and aerobic metabolism (inferred from oxygen consumption) of juvenile C. durissus ingesting prey ranging from 10 to 50% of their own body mass. Time needed for prey ingestion increased with prey size, with prey representing 10 and 20% of snake size being ingested with the same effort. Whole animal rates of oxygen consumption increased linearly with prey size, but at a slower pace for snakes ingesting prey larger than 30% of their body mass. Aerobic factorial power input necessary for prey ingestion increased with prey size, and for snakes ingesting prey representing 50% of their body mass it equaled the aerobic factorial scope for exercise. For the maximum prey size tested, the aerobic derived energy necessary for prey ingestion represented 0.02% of the total energy content of the prey. Within the prey size range we studied, the cost of ingestion did not constitute any constraint on the size of the prey that can be ingested. These constraints are set by morphological (gape size), ecological (predation risk), and, probably, by physiological parameters, as suggested by the tendency of V̇O2 during ingestion to increase at a slower pace at relative larger prey sizes.

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.

Alterations induced by juvenile hormone in glandular cells of the Apis mellifera venom gland I - Application on the larvae (Hymenoptera: Apidae)

Histological analyses were made in order to evaluate the effects of the topic application of a synthetic juvenile hormone (JH-III Sigma) on the development of the venom glands in workers of Apis mellifera. Three experimental groups were used: the first received 1 μl of a dilution of the juvenile hormone in hexane (2μg/μl); the second group received 1 μl of hexane; and the third group, the control, did not receive any kind of treatment. The application was made on larvae at the beginning of the fifth instar and the glands were collected at different developmental stages. The results showed that the application of the diluted hormone, as well as the hexane alone, accelerated gland development in relation to the control group at all developmental stages studied. These data suggest that the juvenile hormone acts on the development of the venom gland; nevertheless, this action could be amplified by the effect of the solvent used in the present work, as well as in other studies concerning this matter.

Juvenile hormone promotes changes in the expression of hypopharyngeal gland proteins of worker Apis mellifera (Hymenoptera: Apidae)

The present investigation compares the protein electrophoreses profiles of the hypopharyngeal glands of 12 and 25 day old Apis mellifera workers, some of which were experimentally treated with an analogue of juvenile hormone in the moment of the emergence while others were not treated. According to the evaluation of the presented variations by four main bands, it is concluded that the analogue juvenile hormone changes the glandular genetic expression pattern, promoting the disappearance of two from the four main bands in 25 day old workers. The effect of this hormone is discussed as an hypopharyngeal maturation inductor, in synergetic action with the bee age acting early in the glandular cycle.

Somatic meiosis and development of the juvenile gametophyte in members of the Batrachospermales sensu lato (Rhodophyta)

Seven populations (six in culture and one sampled directly from nature) of the freshwater red algal families Batrachospermaceae, Lemaneaceae and Thoreaceae were examined, involving three species of Batrachospermum, two of Paralemanea and one of Thorea. All 'Chantransia' stages ultimately produced juvenile gametophytes. The production of juvenile gametophytes in the three populations of Batrachospermum was generally most abundant at 15°C and low irradiances (47-68 μmol photons m-2 s-1). The most abundant gametophyte development in the Paralemanea species was observed at 10°C and low or high irradiances (47-142 μmol photons m-2 s-1). Gametophyte production in Thoreaceae occurred at higher temperatures (20°C) and also at low irradiances. In species of the Batrachospermaceae and Lemaneaceae, the 'elimination cells' can be situated on the basal or suprabasal cell of the juvenile gametophyte, but the position is usually fixed in individual species. The presence and position of the elimination cells remain to be established in Thoreaceae. Our results corroborate a previous study suggesting that the position of elimination cells is such a constant feature that it is of potential diagnostic value at the generic or infrageneric (sectional or specific) level. The characteristics observed in the development of the juvenile gametophytes in species of Batrachospermaceae and Lemaneaceae essentially agreed with general descriptions in the previous studies. The characteristics of the Thoreaceae, with a distinctive developmental pattern of the juvenile gametophyte and the occurrence of two morphological types in the 'Chantransia' stage, support the proposal to elevate it to the ordinal level. Two remarkable observations in Batrachospermum species were the production of numerous juvenile gametophytes from filaments of the same plant of the 'Chantransia' stage and the formation of a system of rhizoidal filaments or cell agglomeration of the juvenile gametophytes, which produced new gametophytes. These two characteristics potentially increase the formation of additional gametophytes under favourable conditions.

Hodgkin disease in adult and juvenile groups from two different geographic regions in Brazil: Characterization of clinicopathologic aspects and relationship with Epstein-Barr virus infection

We analyzed clinicopathologic data, immunophenotype, and Epstein-Barr virus (EBV) status in 96 cases of Hodgkin disease (HD) in juveniles (younger than 20 years) and adults (20 years or older) from 2 distinctive states in Brazil. We studied 34 juvenile (group 1) and 16 adult (group 2) cases from Ceara and 31 juvenile (group 3) and 15 adult (group 4) cases from São Paulo. Ceara has a socioeconomic profile similar to a developing country; São Paulo is in better economic condition. Mixed cellularity (MC) was the major histologic subtype among groups 1 (22 [65%]), 3 (21 [68%]), and 4 (7 [47%]); nodular sclerosis (NS) was more frequent in group 2 (8 [50%]). EBV infection was observed in 61 cases (64%), including the following (among others): group 1, MC, 22 (65%) and NS, 4 (12%); group 2, NS, 3 (19%) and MC, 2 (12%); group 3, MC, 16 (52%) and NS, 1 (3%); and group 4, MC, 7 (47%). There was predominance of EBV+ HD cases in group 1 compared with group 3. HD in Brazilian patients is highly associated with EBV infection, but geographic differences reflect histologic subtypes and age distribution.

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.

Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis

Objective. To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). Methods. Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. Results. A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. Conclusions. We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.

Electrophoretical Protein Profile in Apis mellifera (Hymenoptera; Apidae) Hypopharyngeal Glands under Juvenile Hormone Effect When the Colony is Grown in the Absence of Brood

Twelve-day-old and 25-day-old Apis mellifera workers were treated or not treated with juvenile hormone at the moment of emergence and reared in the colony without brood. Having the brood interference apart, the hormone effect on the hypopharyngeal glands protein expression was determined through the electrophoretical protein profiles of the both groups of bees. In those conditions, the hormone induced changes that were different from the control. Protein bands of 66 and 48 kDa were intensified in the 12-day-old bees, whereas band of 42 kDa was reduced in the 25-day-old bees. That indicated a different effect of the juvenile hormone in the function of bee aging, which promoted a glandular protein activation in the young bees and, in contrast, an inhibitory action in the 25-day-old bees workers.

Juvenile Hormone Effect on the Venom Gland Secretory Cycle in Workers of Apis mellifera (Hymenoptera, Apidae)

The present investigation analyzed the influence of Juvenile Hormone (JH) on the venom glands of Apis mellifera workers through protein dosage and electrophoresis of venom gland extracts of newly emerged workers which were treated with 1 μl JH dissolved in hexane, in concentration of 2μg/μl. Newly emerged workers non-treated and treated with 1 μl hexane were the controls. Both JH and hexane provoke quantitative changes on the gland protein titre and on the protein electrophoretic profile. The disappearance of protein bands in the venom gland extracts of 14 day-old treated workers, a situation normally found only in 35 day-old non-treated workers, suggests that the JH treatment induces a precocious maturation of the worker venom gland.

Influence of IBA and boric acid on rooting of stem-cuttings of Aloysia triphylla (L'Hérit) Britton

Aloysia triphylla (L'Hérit) Britton is a perennial and bushy plant, with simple, entire, lanceolate and whorl shaped leaves and originally from South America. It is used as medicinal plant in Brazil with stomatic and sedative properties. The employment of stem cuttings for propagation of pre-selected plants, acquired great importance, because it eliminates the juvenile phase of seedlings, which can be produced in a shorter period of time. The rooting of stem cuttings is stimulated by auxin and, boric acid supply is essential for growth and development of initial rootlets. This micronutrient is required 48 hours after plant segments have been placed into auxin solution and it can be supplied any time, including the seedling growth period. The experiment was carried out in the Department of Plant Production, UNESP-Botucatu-SP-Brazil, with stem-cuttings of Aloysia triphylla (L'Hérit) Britton, Verbenaceae obtained from the Medicinal and Aromatic Plant Garden. The aim of the work was to verify the influence of growth regulators and boric acid on stem cutting rooting of this species. The 15 cm-stem cuttings, without leaves, were submerged during 24 hs in the following solutions: water; 150 mg.L-1 of IBA; 150 mg.L-1 of IBA+ Boric acid; 250 mg.L-1 of IBA; 250 mg.L-1 of IBA + Boric acid. The statistical design was entirely randomized with 5 treatments and 3 replications, totalizing 15 plots with 10 stem cuttings each. They were planted on propylene trays with vermiculite and kept under spraying condition during twenty five days. The best results were observed in treatment 250 mg.L -1 of IBA+ Boric acid on number of roots, length of roots, rooting percentage, fresh and dry weight of leaves when compared with all other treatments. We can conclude that this treatment is the most suitable for stem cutting rooting of this species.

Economic evaluation of Piaractus mesopotamicus juvenile production in different rearing systems

In this study, the costs and gross income related to the production of pacu Piaractus mesopotamicus juveniles were evaluated. This evaluation took into consideration a semi-intensive rearing, with direct stocking of the larvae into fertilized ponds (IL 0), or an initial intensive larviculture system, in which the larvae were fed in the laboratory for 3 (IL 3), 6 (IL 6), or 9 days (IL 9) before being transferred to the ponds. After 45 days of rearing, a gradual increase in production costs was observed as intensive larviculture time increased. Gross income also increased due to better survival rates (11.0, 25.3, 45.4, and 54.0% for IL 0, IL 3, IL 6, and IL 9, respectively). Therefore, increased profits were obtained under intensive larviculture (US$ 0.27, US$ 6.07, US$ 11.99, and US$ 13.16 per one thousand larvae in treatments IL 0, IL 3, IL 6, and IL 9, respectively). In a larger scale production simulation, the results obtained with initial intensive larviculture also showed evident economic advantages, confirming the feasibility of this system in comparison with the direct stocking of larvae in ponds for the production of pacu juveniles. © 2004 Elsevier B.V. All rights reserved.