Consequências da deriva de clomazone e sulfentrazone em clones de E. grandis x E. urophylla

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito de subdoses dos herbicidas clomazone e sulfentrazone em clones de E. grandis x E. urophylla

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The Treatment of Neonatal Seizures: A Critical Review of the Evidence

In a critical review of the literature to assess the efficacy of monotherapy and subsequent combinant anticonvulsant therapy in the treatment of neonatal seizures, four studies were examined; three randomised control trials and one retrospective cohort study. Each study used phenobarbital for monotherapy with doses reaching a maximum of 40mg/kg. Anticonvulsant drugs used in conjunction with phenobarbitone for combinant therapy included midazolam, clonazepam, lorazepam, phenytoin and lignocaine. Each study used an electroencephalograph for seizure diagnosis and neonatal monitoring when determining therapy efficacy and final outcome assessments. Collectively the studies suggest neither monotherapy nor combinant therapy are entirely effective in seizure control. Monotherapy demonstrated a 29% - 50% success rate for complete seizure control whereas combinant therapy administered after the failure of monotherapy demonstrated a success rate of 43% - 100%. When these trials were combined the overall success for monotherapy was 44% (n = 34/78) and for combinant therapy 72% ( n = 56/78). Though the evidence was inconclusive, it would appear that combinant therapy is of greater benefit to infants unresponsive to monotherapy. Further research such as multi-site randomised controlled trials using standardised criteria and data collection are required within this specialised area.

(Neo)Liberal doses of inequality : advance Australia where?

The relationship between social background and achievement has preoccupied educational researchers since the mid-20th century with major studies in the area reaching prominence in the late 60s. Despite five decades of research and innovation since, recent studies using OECD data have shown that the relationship is strengthening rather than weakening. In this paper, the systematic destabilisation of public education in Australia is examined as a philosophical problem stemming from a fundamental shift in political orientation, where “choice” and “aspiration” work to promote and disguise survivalism. The problem for education however extends far deeper than the inequity in Federal government funding. Whilst this is a major problem, critical scrutiny must also focus on what states can do to turn back aspects of their own education policy that work to exacerbate and entrench social disadvantage.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.

PI3K beta Plays a Critical Role in Neutrophil Activation by Immune Complexes

Neutrophils are activated by immunoglobulin G (IgG)-containing immune complexes through receptors that recognize the Fc portion of IgG (Fc gamma Rs). Here, we used genetic and pharmacological approaches to define a selective role for the beta isoform of phosphoinositide 3-kinase (PI3K beta) in Fc gamma R-dependent activation of mouse neutrophils by immune complexes of IgG and antigen immobilized on a plate surface. At low concentrations of immune complexes, loss of PI3K beta alone substantially inhibited the production of reactive oxygen species (ROS) by neutrophils, whereas at higher doses, similar suppression of ROS production was achieved only by targeting both PI3K beta and PI3K delta, suggesting that this pathway displays stimulus strength-dependent redundancy. Activation of PI3K beta by immune complexes involved cooperation between Fc gamma Rs and BLT1, the receptor for the endogenous proinflammatory lipid leukotriene B-4. Coincident activation by a tyrosine kinase-coupled receptor (Fc gamma R) and a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (BLT1) may provide a rationale for the preferential activation of the beta isoform of PI3K. PI3K beta-deficient mice were highly protected in an Fc gamma R-dependent model of autoantibody-induced skin blistering and were partially protected in an Fc gamma R-dependent model of inflammatory arthritis, whereas combined deficiency of PI3K beta and PI3K delta resulted in near-complete protection in the latter case. These results define PI3K beta as a potential therapeutic target in inflammatory disease.

Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia.

Objectives Nosocomial Pseudomonas aeruginosa pneumonia remains a major concern in critically ill patients. We explored the potential impact of microorganism-targeted adjunctive immunotherapy in such patients. Patients and methods This multicentre, open pilot Phase 2a clinical trial (NCT00851435) prospectively evaluated the safety, pharmacokinetics and potential efficacy of three doses of 1.2 mg/kg panobacumab, a fully human monoclonal anti-lipopolysaccharide IgM, given every 72 h in 18 patients developing nosocomial P. aeruginosa (serotype O11) pneumonia. Results Seventeen out of 18 patients were included in the pharmacokinetic analysis. In 13 patients receiving three doses, the maximal concentration after the third infusion was 33.9 ± 8.0 μg/mL, total area under the serum concentration-time curve was 5397 ± 1993 μg h/mL and elimination half-life was 102.3 ± 47.8 h. Panobacumab was well tolerated, induced no immunogenicity and was detected in respiratory samples. In contrast to Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction, all 13 patients receiving three doses survived, with a mean clinical resolution in 9.0 ± 2.7 days. Two patients suffered a recurrence at days 17 and 20. Conclusions These data suggest that panobacumab is safe, with a pharmacokinetic profile similar to that in healthy volunteers. It was associated with high clinical cure and survival rates in patients developing nosocomial P. aeruginosa O11 pneumonia. We concluded that these promising results warrant further trials.

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Use of in vitro critical inhibitory concentration, a novel approach to predict in vivo synergistic bactericidal effect of combined amikacin and piperacillin against pseudomonas aeruginosa in a systemic rat infection model

PURPOSE: This study was undertaken to explore the use of in vitro critical inhibitory concentration (CIC) as a surrogate marker relating the pharmacokinetic (PK) parameters to in vivo bactericidal synergistic effect [pharmacodynamic (PD)] of amikacin + piperacillin combination against Pseudomonas aeruginosa in a systemic rat infection model. METHODS: The in vitro antibacterial activities of amikacin and piperacillin, alone and in combinations at various ratios of the concentrations, were tested against a standard [5 x 10(5) colony-forming units (CFU)/ml] and a large (1.5 x 10(8) CFU/ml) inoculum of P. aeruginosa ATCC 9027 using a modified survival-time method. The CIC of each individual antibiotic for the different combinations was determined using a cup-plate method. In vivo studies were performed on Sprague-Dawley rats using a systemic model of infection with P. aeruginosa ATCC 9027. PK profiles and in vivo killing effects of the combination at different dosing ratios were studied. RESULTS: An inoculum effect was observed with the antibiotics studied. Synergy was seen against both the inocula at the following concentration ratios: 70% C(ami) + 30% C(pip) and 75% C(ami) + 25% C(pip), where C(ami) and C(pip) are the concentrations of amikacin and piperacillin to produce a 1000-fold decrease in bacterial population over 5 h, respectively. The CIC values determined corroborated with the order of in vitro bacterial killing observed for the antibiotic combinations. The dosing ratio of 12.6 mg/kg amikacin + 36 mg/kg piperacillin (a 70:30 ratio of the individual doses) exhibited the greatest killing in vivo when compared to the other ratios. The PK-PD relationships were described by simple, linear regression equations using the area under the in vivo killing curve as a PD marker and the AUCIC(ami)/CIC(ami) + AUCIC(pip)/CIC(pip), AUC(ami)/CIC(ami) + AUC(pip)/CIC(pip), C(max,ami)/CIC(ami) + C(max,pip)/CIC(pip), and AUCIC(ami)/MIC(ami) + AUCIC(pip)/MIC(pip) as PK markers for the amikacin + piperacillin combination. CONCLUSION: The combination of amikacin and piperacillin exhibited synergistic killing effect on P. aeruginosa that could be modeled using CIC as a surrogate marker relating the PK parameters to in vivo bactericidal effect.

Evidence based drug therapy : are optimal doses and multiple medication therapies realistic in patients with chronic heart failure

Background: Chronic Heart Failure (CHF) has a high mortality and morbidity. Large scale randomised controlled trials have proven the benefits of beta blockade and ACE inhibitors in reducing mortality in patients with CHF and expert guidelines mandate their use. In spite of these recommendations, important therapies are under-prescribed and under-utilised.

Method: 1015 consecutive patients enrolled in CHF management programs across Australia were surveyed during 2005-2006 to determine prescribing patterns in heart failure medications. These patients were followed-up for a period of 6 months.

Results: The survey revealed that beta blockers were prescribed to 80% of patients (more than 85% were on sub-optimal doses) and 70% were prescribed Angiotensin converting enzyme (ACE) inhibitors (approximately 50% were on sub-optimal dose). 19% of patients were prescribed Angiotensin receptor blockers (ARBs). By 6 months <25% of the patients who were on sub-optimal dose beta blockers or ACE inhibitors at baseline, had been up-titrated to maximum dose (p<0.0001). In CHF programs, were nurses were able to titrate medications, 75% of patients reached optimal dose of beta blockers compared to those programs with no nurse-led medication titration, where only 25% of patients reached optimal dose (p<0.004). When examining optimal dosage for any two of these mandatory medications, less patients were on optimal therapy. Beta blockers and ACE inhibitors, were both prescribed in combination in 60% of patients. While beta blockers and ARBs were prescribed to 15% of patients.

Conclusion: Whilst prescribing rates for a single medication strategy of beta blockers, or ACE inhibitors were greater than 70%, an increase in dosage of these medications and utilisation of proven combination therapy of these medications was poor. It is suggested that clinical outcomes for this cohort of patients could be further improved by adherence to evidence-based practice, ESC guidelines, and optimisation of these medications by heart failure nurses in a CHF program. On the basis of these findings and in the absence of ready access to a polypill, focussing on evidence-based practice to increase utilisation and optimal dosage of combination medication therapy is critical.

Quality of life in restless legs syndrome: A systematic review of clinical trials and a critical review of instruments

Restless legs syndrome (RLS) is a neurological movement disorder characterized by sensory symptoms and motor disturbances. While the underlying cause remains unknown, it is suggested that 20–25% of people with RLS are affected seriously enough to require pharmacological treatment. Dopamine agonists (DAs) are the most common treatment and act by increasing the low levels of dopamine to which RLS is often attributed. A growing literature highlights the debilitating and distressing nature of this condition from the patient's perspective. While sleep problems are most commonly reported, the impact of RLS on quality of life (QOL) is wide ranging, affecting relationships with partners, sex life, family life, social life, leisure activities, friendships, everyday activities, concentration, travel, career/work, sleep, and health.

We conducted a systematic review of clinical trials in which DAs have been evaluated in terms of RLS-specific QOL, i.e. their impact on the QOL of people with RLS, and critically reviewed the development history and measurement properties of RLS-specific QOL instruments.

A systematic search using terms synonymous with RLS, DAs and QOL was conducted using Scopus software, which includes MEDLINE, PsycINFO, EMBASE, and CINAHL. Our search covered publications from 2000 (prior to which RLS-specific QOL measures did not exist) to August 2009. Trials were included in our review if they evaluated DAs for the treatment of adults with RLS and reported evaluation using an RLS-specific QOL measure. We also ran citation searches to identify papers reporting the development history and measurement properties of the identified RLS-specific QOL instruments.

Three measures of RLS-specific QOL have been developed in recent years and are reviewed here: the Restless Legs Syndrome Quality of Life (RLSQOL) questionnaire, the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI), and the Quality of Life Restless Legs Syndrome (QOL-RLS) measure. Critical review indicates that each has limitations (particularly in terms of published developmental history and content validity). Eleven trials of DAs were identified that included assessment of RLS-specific QOL (nine using the RLSQOL and two using the QOL-RLS). In all studies, significant improvements in RLS-specific QOL were observed, although these were mostly short term (12 weeks) and large placebo effects were also noted.

In people with RLS, the use of DAs has been shown to improve RLS-specific QOL. Longer-term, large-scale studies may be needed to confirm these findings and demonstrate statistically significant improvements in RLS-specific QOL at lower doses. Further development of the RLS-specific QOL measures is needed to ensure that the full impact of RLS (and the full benefit of new treatments) on aspects of life identified as important to individuals is captured in future studies.

Germinação de sementes de guandu sob efeito da disponibilidade hídrica e de doses subletais de alumínio

O objetivo deste trabalho foi verificar a germinação de sementes das cultivares de guandu, IAPAR 43-Aratã e IAC Fava Larga, sob efeito da disponibilidade hídrica e de doses subletais de alumínio. Os experimentos foram instalados na Faculdade de Ciências Agrárias e Veterinárias-UNESP, em Jaboticabal (SP), no período de março a maio de 2002. As sementes foram colocadas em caixas de germinação, previamente esterilizadas, revestidas com uma folha de papel germitest umedecido com diferentes concentrações de PEG 6000 (0,0; -0,6; -0,9; -1,2 e -1,5 MPa) e de sulfato de alumínio (0,0; 2,5; 5,0; 7,5; e 10,0 mmol.dm-3). O delineamento experimental utilizado foi o inteiramente casualizado em arranjo fatorial 2 x 5 x 5 (cultivares x disponibilidades hídricas x alumínio), com quatro repetições de 50 sementes. Para complementar a análise estatística foram realizadas análises multivariadas de agrupamento e componentes principais. O experimento foi desenvolvido em câmara de germinação, na temperatura de 25 ºC. A porcentagem de germinação foi verificada no 4.º e 10.º dias após a semeadura. No 10.º dia, as plântulas foram separadas em plúmulas e raízes primárias, para determinar a massa seca. A disponibilidade hídrica foi limitante para a germinação e o crescimento inicial. O efeito do alumínio associado ao estresse hídrico foi evidenciado somente até -0,9 MPa. As concentrações menos elevadas de alumínio estimularam o desenvolvimento das plântulas em condições de estresse hídrico até -0,6 MPa. Os efeitos simultâneos da disponibilidade hídrica e do alumínio reduziram a germinação de sementes da cv. IAC Fava Larga e o crescimento das raízes da cv. IAPAR 43-Aratã.

APPLICATION of THE HAZARD ANALYSIS and CRITICAL CONTROL POINT (HACCP) SYSTEM on THE MUSHROOM PROCESSING LINE FOR FRESH CONSUMPTION

The Hazard Analysis and Critical Control Point (HACCP) is a preventive system that intends to guarantee the safety and harmlessness of food. It improves the quality of products as it eliminates possible defects during the process, and saves costs by practically eliminating final product inspection. This work describes the typical hazards encountered on the mushroom processing line for fresh consumption. Throughout the process, only the reception stage of mushrooms has been considered a critical control point (CCP). The main hazards at this stage were: the presence of unauthorised phytosanitary products; larger doses of such products than those permitted; the presence of pathogenic bacteria or thermo-stable enterotoxins. Putting into practice such knowledge would provide any industry that processes mushrooms for fresh consumption with a self-control HACCP-based system for its own productions.

Efeitos de doses não equidistantes de N, P, K nas concentrações destes macronutrientes na folha e na produção do milho (Zea mays L.)

Os experimentos foram conduzidos, em um podzólico de Lins e Marília - variação Lins, de textora barrento-arenosa, localizado no Município de Monte Azul Paulista, SP. O híbrido de milho duplo H-6999B foi utilizado. Cada experimento constou de 5 tratamentos e de 4 repetições. Os níveis de nitrogênio foram: 0, 50, 100, 200 e 400 kg/ha, sendo aplicados também90 kg/ha de P²O5 e 50 kg/ha de K2O. Os níveis de fósforo foram: 0,40, 80, I60 e 320 kg/ha de P²O5, sendo aplicados também 100 kg/ha de N e 50 kg/ha de K2O. Os níveis de potássio foram: 0, 25, 50, 100 e 200 kg/ha de K2O, sendo aplicados também 100 kg/ha de N e 90 kg/ha de P²O5. A aplicação tanto das doses de fósforo comodas de nitrogênio fez aumentar a produção de milho, a qual foi da ordem de 3 a 7 vezes superior à média de produção do Estado de São Paulo. A dose econômica e a sua consequente produção, determinadas pelas equações de Mitscherlichr-Pimentel Gomes foram: para o fósforo, de 253 kg/ha de P²O5 correspondente a urna produção de o.877 kg/ha de milho em grão; para o nitrogênio, foi de 228 kg/ha de N correspondente a uma produção de 11.100 kg/ha de milho e para o potássio, foi de 62 kg/ha de K2O correspondente a urna produção de 9-252 kg/ha de milho. Os níveis críticos econômicos, nas folhas, determinados pelas equações de MALAVOLTA & PIMENTEL GOMES (1961) e correspondentes às doses econômicas, foram de: 0,293% de P, de 3,27% de N e de 2,07% de K. A folha escolhida, ou seja, aquela oposta à espiga mais alta, reflete bem o estado nutricional da planta e consequentemente o nível de fertilidade do solo.

Doses de zinco em diferentes condições de acidez de um solo de cerrado. II. Nível crítico na planta

In this work it was demanded to verify the zinc critical levels in soybean plants cultivated in a Dark-Red Latosol. So the experiment was carried out in vases with 4 liters of soil, which has received five doses of Zn (0, 1.0, 2.0, 3.0 and 4.0 ppm) in three correction levels. It was verified that the critical levels of the nutrient in plant (for 90% from highest production) was between 36 and 53 ppm to the dry matter yield and grains in treatments with correction.