The effect of 4-chlororesorcinol on the endogenous levels of IAA, ABA and oxidative enzymes in cuttings

Treatment of bean cuttings with 4-chlororesorcinol (4-CR), known to increase the number of roots and extend their distribution, prevented the accumulation of free indol-3-yl-acetic acid (IAA) in the hypocotyls within 24 h after cutting preparation. In mung bean there was no change in the distribution (upper half vs. 1 ower half of the hypocotyl) of IAA within the hypocotyl as a result of the treatment. In bean cuttings the treatment with 4-CR prevented the accumulation of IAA in the bottom of the cutting. Oxidation of IAA as a measure of IAA oxidase activity in bean was enhanced appreciably by 4-chlororesorcinol. The level of abscisic acid in mung bean, on the other hand, remained 3-4 fold higher than in the control, yet still about 50% lower than the zero time level. In untreated mung bean cuttings the activity of peroxidase increased after cutting preparation. In contrast, the activity of peroxidase in 4-Cr-treated cuttings was consistently lower. In order to relate to the effect of exogenously applied auxin the level of peroxidase was measured also in indol-3-yl-butyric acid-treated cuttings. The overall peroxidase activity in IBA-treated cuttings was not affected. However, when assaying for the different isozymes the drop in peroxidase activity was most evident in the inducible basic isoperoxidases both in 4-CR and IBA treatments. It appears that the exposure to 4-CR exerts an effect that is similar to that of exogenously applied auxin, affecting the activity of basic peroxidases and enhancing the oxidation of endogenous IAA, thus allowing the organization of the primordia.

Submissão às recomendações do BI-RADS™ por médicos e pacientes: análise preliminar de 3.000 exames realizados em uma clínica particular

O Breast Imaging Reporting and Data System (BI-RADS™) do American College of Radiology é um sistema que objetiva padronizar o laudo mamográfico, reduzir os fatores de confusão na descrição e interpretação das imagens e facilitar a emissão do resultado final do exame. OBJETIVO: Buscar identificar o grau de submissão das mulheres e médicos às recomendações do BI-RADS em Goiânia, GO. MATERIAIS E MÉTODOS: Foram avaliadas, prospectivamente, 3.000 mulheres submetidas à mamografia em um serviço radiológico particular em Goiânia (janeiro a dezembro de 2002). Os laudos foram emitidos de acordo com o BI-RADS. As mulheres classificadas nas categorias 0, 3, 4 e 5 foram acompanhadas por contato telefônico. RESULTADOS: Mulheres que se recusaram a seguir orientação: categorias 0 (11,5%), 3 (13,8%), 4 (28%) e 5 (0%). Não houve orientação médica para seguir recomendação: categorias 0 (18,2%), 3 (17%), 4 (20%). Mulheres que se submeteram à recomendação: categorias 0 (1,8%), 3 (5,7%), 4 (40%), 5 (100%). Perdidas no seguimento: categorias 0 (68,5%), 3 (39%) e 4 (12%). CONCLUSÃO: É baixa a submissão às recomendações do BI-RADS nas categorias 0 e 3, e moderada na categoria 4. Aproximadamente 30% das mulheres classificadas na categoria 0 não se submeteram à avaliação adicional por imagem, por recusa própria ou por falta de orientação médica.

Musiikkikasvatuskansio 3-5 - vuotiaiden varhaiskasvatuksessa päiväkodissa

Opinnäytetyöni haasteena oli työstää musiikkikasvatuskansio, joka on tarkoitettu päiväkodissa työskenteleville kasvattajille 3-5 - vuotiaiden lasten musiikkikasvatuksen tukena. Musiikkikasvatuskansion laatimisen idea lähti liikkeelle työyhteisön tarpeesta kehittää osaamistaan musiikkikasvatuksen osa-alueella. Myös tekijän oma kiinnostus musiikkiin sekä ammatillinen kehittyminen musiikkikasvatuksessa loivat ideaa musiikkikasvatuskansion kokoamiselle. Opinnäytetyössäni yhdistyvät käytännön toteutus musiikkikasvatuskansion kautta sekä sen raportointi. Opinnäytetyö on työelämälähtöinen ja käytännönläheinen, jossa osoitan aiheen tietojen ja taitojen hallintaa. Opinnäytetyöni tavoitteena oli käytännön toiminnan ohjeistaminen, opastaminen, toiminnan järjestäminen ja järkeistäminen laatimani musiikkikasvatuskansion pohjalta. Tavoitteena oli, että musiikkikasvatuskansion käyttäjälle hahmottuu teoriassa sekä käytännön esimerkein selkeä kuva musiikkikasvatustoiminnasta ja kynnys musiikin käyttämiseen aktiivisena työvälineenä päiväkodin varhaiskasvatuksessa olisi matalampi. Tavoitteena oli luoda kasvattajalle rohkeutta tarttua musiikin toiminnallisiin menetelmiin, vaikka ei tuntisi musiikkia vahvaksi osa-alueeksi omassa työssään. Musiikkikasvatuskansio sisältää lyhyen teoriaosuuden yleisesti musiikkikasvatuksesta ja sen merkityksestä varhaiskasvatuksessa. Muu osa kansiosta on jaettu kolmeen osioon, joissa on valmiita esimerkkejä musiikkikasvatustoiminnan tueksi sekä niihin liittyvät laulut ja laululeikit nuotteineen. Osiot on jaettu ikävaiheittain 3-4 - vuotiaiden ja 4-5 - vuotiaiden musiikkikasvatukseen sekä yleiseen käytännön osioon, jotta musiikkikasvatuskansio olisi mahdollisimman selkeä, helppokäyttöinen ja monipuolinen.Musiikkikasvatuskansio on suunnattu 3-5 - vuotiaiden lasten musiikkikasvatukseen päiväkodissa, mutta sitä on mahdollisuus soveltaa ja laajentaa koskemaan kaikkia työyhteisössäni toimivia lapsiryhmiä, kuten esimerkiksi erityistä tukea ja kasvatusta tarvitsevat lapset, eri kieli- ja kulttuuritaustaiset lapset sekä alle 3-vuotiaiden lasten musiikkikasvatus.

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.

Mantenimiento de catéteres venosos periféricos durante más de 4 dias. En busca de la mejor evidencia

Antecedentes: Desde 1981, los Centers for Disease Control and Prevention (CDC) recomiendan sustituir los catéteres venosos periféricos cada 3-4 días para disminuir el riesgo de flebitis, infección y bacteriemia de catéter. Objetivo: El objetivo de esta revisión sistemática es determinar la efectividad de esta intervención mediante la evaluación de la evidencia científica disponible. Material y método: Se realizó una exploración de diferentes bases de datos electrónicas y se revisaron manualmente varios índices desde 1981 a 200l. Para identificar los trabajos más relevantes y descartar los de menor calidad se empleó un sistema de evaluación cualitativa que permitió la discriminación de tres grupos de estudios, de mayor a menor calidad metodológica y, por tanto, de riesgo de sesgo. Resultados y conclusiones: De los originales captados, 12 fueron sometidos a valoración crítica. Un 33% se clasificó como metodológicamente insuficiente y un 41% obtuvo una puntuación intermedia, con lo que sus resultados debían interpretarse con cautela. Los trabajos cualitativamente más significativos no demuestran que sea necesario sustituir de forma rutinaria los catéteres venosos periféricos, como recomiendan los CDC.

Síntese e atividade fitotóxica de 2-fenil-6,7-exo-isopropilidenodioxi-8-oxabiciclo [3.2.1]oct-2-eno

The [3+4] cycloaddition between furan and the oxyallyl cation generated from 1-bromo-1-phenylpropan-2-one (4), resulted in the formation of 2-phenyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (5) in 30% yield. This compound was further converted into 2-phenyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]oct-2-ene (13) in 35.4% yield. The selective effect of compound (13) and its isomer 3-phenyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]oct -2-ene (1a) on the radicle growth of Sorghum bicolor L. (sorghum) and Cucumis sativus L. (cucumber) were evaluated. For both plants, compound 13 showed to be more potent than its isomer 1a.

Síntese de novos herbicidas derivados do 1,2alfa,4alfa,5-tetrametil-8-oxabiciclo[3.2.1]oct-6-en-3-ona

In this paper we report the synthesis of biologically active compounds through a [3+4] cycloaddition reaction to produce the main frame structure, followed by several conventional transformations. The 1,2alpha,4alpha,5-tetramethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (11) obtained from a [3+4] cycloaddition reaction was converted into 1,2alpha,4alpha,5-tetramethyl-6,7-exo-isopropylidenedioxi-8 -oxabicyclo[3.2.1]octan-3-one (13) in 46% yield. This was further converted into the alcohols 1,2alpha,4alpha,5-tetramethyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (14), 1,2alpha,4alpha,5-tetramethyl-6,7-exo-isopropylidenedioxi-8 -oxabicyclo[3.2.1]octan-3beta-ol (15), 1,2alpha,4alpha,5-tetramethyl-3-butyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (17), 1,2alpha,4alpha,5-tetramethyl-3-hexyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (18) and 1,2alpha,4alpha,5-tetramethyl-3-decyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]octan-3 alpha-ol (19). Dehydration of 17, 18 and 19 with thionyl chloride in pyridine resulted in the alkenes 20, 21 and 22 in ca. 82% - 89% yields from starting alcohols. The herbicidal activity of the compounds synthesized was evaluated at a concentration of 100 µg g-1. The most active compound was 21 causing 42,7% inhibition against Cucumis sativus L.

Síntese do monastrol e novos compostos de Biginelli promovida por In(OTf)3

In this paper, we describe a practical route for the synthesis of Biginelli compounds using In(OTf)3. To study the generality of this catalyst, several examples using aromatic aldehydes, 1,3-dicarbonyl compounds, urea, and thiourea were investigated. The present procedure provides an efficient modification of the classical Biginelli reaction, namely short reaction times and simple work-up, that not only preserves the simplicity of the original protocol but also produces excellent yields of 3,4-dihydropyridin-2(1H)-ones. Thiourea was used with similar success to provide the corresponding 3,4-dihydropyridin-2(1H)-thiones. In this case, the (+/-)-monastrol, antimitotic agent, was obtained in 92% yield and new thio analogues were synthesized.

Síntese e caracterização de copolímeros de cadeia lateral derivados de acrilatos de 4,5-di-hidroisoxazol e do (-)-mentol

Five monomers 5-[4-(5-cyano-4,5-dihydroisoxazol-3-yl)phenoxy]undecyl acrylate (7a); n-alkyl 3-{4-[5-(acryloyloxyundecyl)oxyphenyl]}-4,5-dihydroisoxazole-5-carboxylate (7b,c for n-butyl and n-hexyl, respectively); 3-{4-[5-(acryloyloxyundecyl) oxyphenyl]}-4,5-dihydroisoxazole-5-carboxylic acid (7d) and (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl acrylate (9) and the corresponding copolymers 10a-d,11 and homopolymers 12 from 7a and 13 from 9 were designed and synthesized. Except for acrylate 9 which is derived from (-)-menthol, all of the monomers belong to the series containing the isoxazoline ring linked to the acrylate unit by a flexible spacer chain of eleven methylene units. They presented low glass temperature and despite birefringence behavior, these copolymers showed no mesomorphic properties.

MÉTODO ALTERNATIVO PARA A SÍNTESE E MECANISMO DE 2-(1,3-DITIANO-2-ILIDENO)-ACETONITRILA

We report an alternative method for the synthesis of 2-(1,3-dithian-2-ylidene)-acetonitrile using 3-(4-chlorophenyl)-3-oxopropanenitrile and carbon disulfide as starting materials. The methanolysis of the intermediate 3-(4-chlorophenyl)-2-(1,3-dithian-2-ylidene)-3-oxopropanenitrile occurs via three possible intermediates, leading to the formation of the product at a 75% overall yield. Molecular modeling simulation of the reaction pathway using B3LYP 6-311G++(2df,2p) justified the proposed reaction mechanism.

Sinfonia n:o 4 Es "Romanttinen" : 1878-1880 laitos = Symfoni n:o 4 Ess "Den Romantiska" : 1878-1880 version

Soitinnus: orkesteri.

Simulação das perdas de água por evaporação e arraste, no aspersor NY-7 (4,6 mm x 4,0 mm), em sistemas de aspersão convencional

As perdas de água por evaporação e arraste em sistemas de irrigação por aspersão podem assumir valores consideráveis, reduzindo a eficiência do sistema. Os objetivos do presente trabalho foram avaliar a capacidade preditiva de cinco modelos empíricos para estimar perdas de água por evaporação e arraste em aspersores modelo NY-7 (bocais de 4,6 mm x 4,0 mm), trabalhando sob diferentes condições operacionais e ambientais, e ajustar modelos específicos para o aspersor NY-7. Comparando os resultados medidos em ensaios de campo, com os resultados simulados, foi possível concluir que os cinco modelos empíricos considerados apresentaram pouca ou nenhuma adequação, tanto para os ensaios com um único aspersor (quadrado do erro-médio de 5,27; 20,70; 5,07; 6,95 e 7,06% para os modelos empíricos 1; 2; 3; 4 e 5, respectivamente) quanto para os ensaios com linhas laterais contendo aspersores (quadrado do erro-médio de 7,41; 24,43; 6,72; 3,16 e 2,9% para os modelos empíricos 1; 2; 3; 4 e 5, respectivamente). Comparados aos cinco modelos empíricos considerados, os novos modelos ajustados apresentaram menores erros, indicando que a aplicação de modelos empíricos deve ser limitada às condições de operação (diâmetro de bocal, pressão de operação, etc.) similares àquelas em que os modelos foram desenvolvidos.

Prevalência da lesão HPV induzida em canal anal de mulheres com neoplasia intraepitelial cervical 2 e 3: um estudo de corte transversal

OBJETIVO: Determinar a prevalência da lesão anal induzida por HPV em mulheres com neoplasia intraepitelial cervical grau 2/3 (NIC2/3).MÉTODOS: Estudo transversal, realizado no período de dezembro de 2008 a junho de 2009, no Estado de Pernambuco, nordeste do Brasil. Foram incluídas no estudo apenas mulheres com diagnóstico de NIC2/3 confirmado por biópsia e excluídas aquelas que não realizaram exame na primeira visita. As amostras para identificação do DNA de HPV anal por PCR e citologia anal foram coletadas com escovinha endocervical. A biópsia anal foi realizada nos casos de citologia anal anormal ou alterações maiores na anuscopia de alta resolução (AAR).RESULTADOS: Das AARs, 32,1% (n=37/115) foram normais e 63,5% (n=73/115) exibiram epitélio acetobranco. Vinte e dois por cento das citologias anais (n=26/115) foram anormais. Dentre elas, 12,2% (14/26) corresponderam à lesão intraepitelial anal de baixo grau e 3,4% (n=4/26), a lesão intraepitelial anal de alto grau. Foram realizadas 22 biópsias, das quais 13,7% (n=3/22) tiveram diagnóstico de neoplasia intraepitelial anal (NIA2) e 9% (n=2/22), NIA 3. Identificou-se 72,1% (n=83/115) de DNA do HPV nas amostras.CONCLUSÃO: Mulheres com NIC2/3 apresentam elevada prevalência de infecção por HPV e lesão HPV induzida em canal anal.

Assessing bovine babesiosis in Rhipicephalus (Boophilus) microplus ticks and 3 to 9-month-old cattle in the middle Magdalena region, Colombia

Babesia sp. is a protozoan hemoparasite that affects livestock worldwide. The Colombian Middle Magdalena is an enzootic region for babesiosis, but there is no previous research providing detail on its transmission cycle. This study aims to assess some Babesia sp. infection indicators in cattle and ticks from the area, by using direct microscopic and molecular techniques to detect the infection. In the cattle, 59.9% and 3.4 % positivity values for B. bigemina and mixed infection (B. bovis + B. bigemina) were found respectively. In ticks, the positivity of B. bigemina reached 79.2% and 9.4% for the mixed infection. The degree of infestation in the region was 3.2 ticks per bovine. There was positive correlation between tick control acaricide frequencies and infestation in bovines. This leads us to infer that control periodicity greater than 90 days, in stable zones, is an abiotic factor that benefits the acquisition of protective immunity in calves, the natural control of the infection and eventual disease absence. It is necessary to monitor the disease by applying new entomological and parasitological indicators showing the complexity of this phenomenon.

Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F1α (6-keto-PGF1α; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM22-52, a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP8-37, a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with NG-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K+ channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K+ channels), and apamin (Ca2+-activated channel blocker) did not affect AM-induced relaxation. AM increased nitrate levels and 6-keto-PGF1α in rat CSM. The major new contribution of this research is that it demonstrated expression of AM and its receptor in rat CSM. Moreover, we provided evidence that AM-induced relaxation in this tissue is mediated by AM receptors by a mechanism that involves the nitric oxide-cGMP pathway, a vasodilator prostanoid, and the opening of voltage-dependent K+ channels.