Selectivity of herbicides applied to Brazilian tree species at post-emergence

The presence of weeds in silvicultural systems has been considered one of the main obstacles to the success of projects designed to recover degraded areas. The aim of this study was to evaluate the selectivity of herbicides applied at post-emergence in the initial growth of seedlings of capixingui (Croton floribundus), açoita-cavalo (Luehea divaricata), and guaritá (Astronium graveolens), in the municipalities of Jaboticabal and Junqueirópolis, state of São Paulo. The experimental design was completely randomized, with four replications, and the treatments consisted of herbicides (g a.i.·ha-1) clethodim + phenoxaprop-p-ethyl (50 + 50), sethoxydim (184), quizalofop-p-ethyl (75), nicosulfuron (50), fluazifop-p-butyl (125), fomesafen (225), haloxyfop-methyl (48), bentazon (720), chlorimuron-ethyl (15), in addition to control without herbicide. The characteristics analyzed were: plant height increase and visual phytointoxication at 7, 14, 21, 28, 35, and 42 days after herbicide application. At the end of the experiment, the shoots of the plants were removed to assess shoot dry matter. The herbicides clethodim + fenoxaprop-p-ethyl, fluazifop-p-butyl, and quizalofop-p-ethyl showed selective potential for the species capixingui, açoita-cavalo, and guaritá. The herbicide chlorimuron-ethyl caused mild intoxication symptoms when applied to seedlings of capixingui and açoita-cavalo; also, it was not selective for the guaritá species grown in Jaboticabal. All species showed selectivity to the herbicides sethoxydim, fomesafen, haloxyfop-methyl, and nicosulfuron, as their growth and initial development were not influenced. The herbicide bentazon caused high percentages of injury to açoita-cavalo plants in both cultivation places, but it did not influence the growth and development of the species.

Taurolidina para prevenir infecciones asociadas a catéter venoso central en niños con insuficiencia intestinal: experiencia preliminar en un hospital terciario chileno / Taurolidine for the prevention of catheter-related infections in children with intestinal insufficiency: preliminary experience in a Chilean tertiary hospital

INTRODUCCIÓN: Taurolidina es una molécula con propiedades anti-endotóxicas, antimicrobianas y anti-inflamatorias, que inhibe la adhesión bacteriana, lo que ha permitido usarla como terapia de sellado en catéter venoso central de larga duración (CVC) para prevenir infecciones del torrente sanguíneo asociadas a CVC (ITS-CVC). OBJETIVO: Dar a conocer una experiencia preliminar, la primera en Chile, con taurolidina como terapia de sellado para prevenir ITS-CVC y reportar su eficacia. MÉTODO: Se instiló una solución en base a taurolidina en el CVC de tres niños con insuficiencia intestinal, dependientes de alimentación parenteral, atendidos en un hospital terciario de la Región de Valparaíso, y se comparó la tasa de ITS-CVC antes y después de su uso mediante un análisis retrospectivo. RESULTADOS: en los dos pacientes que iniciaron terapia de sellado inmediatamente después de instalado el CVC, la tasa de ITS-CVC se logró llevar a cero, mientras que, en el tercero, portador de un CVC instalado 9 meses antes, con ITS-CVC recurrentes, un nuevo episodio de ITS-CVC obligó a suspender la profilaxis. CONCLUSIONES: La terapia de sellado con solución en base a taurolidina previno las ITS-CVC cuando ésta se inició al momento de instalarse el CVC, no así en un CVC antiguo con ITS-CVC recurrentes.

BACKGROUND: Taurolidine is a molecule with anti-endotoxic, anti-microbial and anti-inflammatory properties that inhibits bacterial adhesion, allowing for its use as lock therapy for the prevention of catheter-related bloodstream infections (CRBSI) in long-term central venous catheters (CVC). AIM: To report a preliminary experience, the first one in Chile, using lock therapy with taurolidine for the prevention of CRBSI and to report its efficacy. METHOD: A taurolidine-based solution was instilled in the CVC of three children with intestinal insufficiency dependent on parenteral nutrition, attended in a Chilean tertiary hospital, and the rate of CRBSI before and after its use was compared in retrospect. RESULTS: In the two patients who started lock therapy immediately after the installation of their CVC, the rate of CRBSI was brought to zero, whereas in the third patient, who had a 9 months-old CVC with a recurrent CRBSI history, an intercurrent CRBSI forced discontinuation of the prophylaxis. CONCLUSIONS: Lock therapy with a taurolidine-based solution prevented CRBSIs when it was begun immediately after installing the CVC, in contrast with an old CVC with a history of recurrent CRBSIs.

Taurolidina, un antiséptico para la prevención de infecciones asociadas a catéter venoso central / Taurolidine, an antiseptic for the prevention of central venous catheter-related infections

Resumen Taurolidina es un antiséptico de amplio espectro usado como solución de terapia de sellado (lock therapy) en adultos y niños portadores de catéter venoso central de larga duración (CVC) para prevenir las infecciones asociadas a CVC (IACVC). No induce desarrollo de resistencia y tiene efectos adversos leves y fugaces, lo que lo convierte en una alternativa, tanto como terapia de sellado como para la profilaxis de las IACVC, en este grupo de pacientes.

Taurolidine is a broad-spectrum antiseptic used as lock therapy solution in adult and pediatric patients with long term central venous catheters (CVC) for the prevention of catheter related bloodstream infections (CRBSI). Taurolidine doesn't induce the resistant development and has only minor and brief side effects, which makes it an alternative both as a lock therapy and for the prevention of CRBSI in this group of patients.

Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin / 药学学报

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.

Comparação entre o sumatriptano, a trimebutina, o meloxicam e a associação dos três fármacos no tratamento agudo de enxaqueca / Comparison among sumatriptane, trimebutine, meloxicam and the association of those drugs in the acute treatment of migraine

JUSTIFICATIVA E OBJETIVOS: A crise aguda de migrânea geralmente leva a grande incapacidade econômica e social para aqueles que sofrem deste transtorno. A fisiopatologia é complexa e envolve múltiplos mecanismos centrais e periféricos. O tratamento agudo tem como objetivo aliviar a dor e os fenômenos associados como a náusea e fotofobia, sem causar efeitos adversos importantes. Apesar do desenvolvimento de fármacos específicos como os triptanos, para o tratamento agudo, a sua eficácia ainda é baixa. O objetivo deste estudo foi comparar a eficácia e a tolerância da trimebutina, meloxicam, sumatriptano e a associação dos três fármacos no tratamento das crises agudas de migrânea de moderada a forte intensidade.MÉTODO: Após aprovação pelo Comitê de Ética das Instituições foram incluídos neste estudo prospectivo, duplamente encoberto e aleatório, 50 pacientes, sendo 43 mulheres e 7 homens, com idade entre 18 e 65 anos, portadores de migrânea com ou sem aura, que utilizavam medicação profilática, exceto anti-inflamatórios não esteroides (AINES). Foram tratadas quatro crises de migrânea de moderada a forte intensidade de cada paciente, com 200 mg de trimebutina, 50 mg de sumatriptano, 15 mg de meloxicam ou com a associação de 200 mg de trimebutina, 50 mg de sumatriptano e 15 mg de meloxicam. Os pacientes foram aleatorizados em 4 grupos de acordo com a ordem de chegada, de modo que o primeiro paciente incluído recebeu trimebutina para a primeira crise, sumatriptano para a segunda crise, meloxicam para a terceira crise e a associação entre os 3 fármacos para a quarta crise. O segundo paciente incluído recebeu sumatriptano para a primeira crise, meloxicam para a segunda superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.crise, a associação para a terceira crise e a trimebutina para a quarta crise, e assim sucessivamente. A intensidade da crise de migrânea foi avaliada a partir da ingestão da cápsula com escala categorizada verbal na qual: 0 - sem dor, 1 - cefaleia leve, 2 - cefaleia moderada e 3 - cefaleia intensa. Cada paciente foi orientado para preencher o relatório de crise para cada crise tratada, na qual anotava a intensidade da cefaleia, a presença de náusea, fotofobia e dos efeitos adversos, e o uso da medicação de resgate, 100 mg de indometacina por via retal. RESULTADOS: Completaram o estudo 42 pacientes. Em uma hora 9,5% dos pacientes que utilizaram a associação dos fármacos estavam livres da dor, comparados com 14,2% com a trimebutina e sumatriptano e 2,4% com o meloxicam (p = 0,479). Em duas horas 21,4% dos pacientes que usaram a associação estavam livres da dor, comparados com 11,9% com a trimebutina, 26,1% com sumatriptano e 23,8% com o meloxicam (p = 0,555). Tanto a associação trimebutina, sumatriptano e meloxicam como os fármacos trimebutina, sumatriptano e meloxicam isolados foram efetivos para controlar a náusea e fotofobia após 1 e 2h para náusea (p = 0,157 e 0,587) e fotofobia (p = 0,671 e 0,929, embora sem diferença estatisticamente significativa entre eles. Dez pacientes em uso da associação dos fármacos, 6 em uso da trimebutina, 5 em uso do sumatriptano e 5 em uso do meloxicam relataram efeitos colaterais. CONCLUSÃO: Este estudo demonstrou que a associação sumatriptano, meloxicam e trimebutina não foi superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.

BACKGROUND AND OBJECTIVES: Acute migraine crisis often leads to major economic and social disability for those suffering from such syndrome. Pathophysiology is complex involving several central and peripheral mechanisms. The acute treatment aims at evaluating pain and associated phenomena, such as nausea and photophobia, without causing major adverse effects. Notwithstanding the development of specific drugs for the acute treatment, such as triptanes, their efficacy is still low. This study aimed at comparing efficacy and tolerance of trimebutine, meloxicam, sumatriptane and the association of such drugs to treat moderate to severe acute migraine crises.METHOD: After the Institutions? Ethics Committee approval, participated in this prospective, double-blind and randomized study 50 patients, being 43 females and 7 males, aged between 18 and 65 years, with migraine with or without aura, under prophylactic medication, except non-steroid anti-inflammatory drugs (NSAIDS). Patients were treated for 4 moderate to severe migraine crises with 200 mg trimebutine, 50 mg sumatriptane, 15 mg meloxicam, or with the association of 200 mg trimebutine, 50 mg sumatriptane and 15 mg meloxicam. Patients were randomized in 4 groups according to their arrival, so that the first patient included received trimebutine for the first crisis, sumatriptane for the second crisis, meloxicam for the third crisis and the association of the three drugs for the fourth crisis. The second patient included received sumatriptane for the first crisis, meloxicam for the second crisis, the association for the third crisis and trimebutine for the fourth crisis, and so on and so forth. Migraine crisis intensity was evaluated as from the ingestion of the first tablet with verbal categorized scale where: 0 = no pain, 1 = mild headache, 2 = moderate headache, 3 = severe headache. All patients were oriented to fill a crisis report for each treated crisis, where they would record headache intensity, presence of nausea, photophobia and adverse effects and the use of rescue medication, 100 mg of rectal indometacin.RESULTS: Forty-two patients completed the study. In one hour 9.5% of patients using the association of drugs were free of pain, as compared to 14.2% with trimebutine and sumatriptane and 2.4% with meloxicam (p = 0.479). In two hours 21.4% of patients using the association were free of pain, as compared to 11.9% with trimebutine, 26.1% with sumatriptane and 23.6% with meloxicam (p = 0.555). Both the association of trimebutine, sumatriptane and meloxicam and trimebutine, sumatriptane and meloxicam alone were effective to control nausea and photophobia after 1 and 2 h for nausea (p = 0.157 and 0.587) and photophobia (p = 0.671 and 0.929) although without statistically significant difference among them. Ten patients under the association of drugs, 6 under trimebutine, 5 under sumatriptane and 5 under meloxicam have reported side effects. CONCLUSION: This study has shown that the association of sumatriptane, meloxicam and trimebutine was not better than each of those drugs alone to control pain, nausea and photophobia during moderate to severe migraine crises. In addition, the combination of drugs has shown a higher incidence of adverse effects.

Synthesis and quantitative structure activity relationship [QSAR] study of new 3-allyl-5-substituted-3,4,5,6-tetrahydro-2H-l,3,5-thiadiazine-2-thiones of a potential antimicrobial activity

Fifteen new 3-allyl-5-substituted-3,4,5,6-tetrahydro-2H-l,3,5-thia diazine-2-thiones were synthesized by the reaction of allylamine with carbon disulfide and potassium hydroxide, followed by formaldehyde and appropriate primary amine such as alkyl, aralkylamines, glycine, L-alanine or ethyl glycine ester. The title compounds were tested, in vitro, for antimicrobial activity against gram-positive bacteria [Bacillus cereus, Staphylococcus aureus, Micrococcus leuteus], Gram-negative bacteria [Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa], and some fungi [Aspergillus flavus, Aspergillus niger, Candida albicans, Geotrichum candidum, Scopulariopsis brevicaulis and Tricho-phyton rubrum], using agar disc method. Quantitative structure activity relationship study was performed using the log form of MIC against Scopulariopsis brevicaulis fungi and some physico-chemical descriptors [MR, L, and Fr] of substituents at N-5 position. The log MIC were found to be negatively linearly correlated with MR and L and positively linearly correlated with Fr

Synthesis and antimicrobial activity of some 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives

Twelve new 3-[isobutyl]-5-substituted-tetrahydro-2H-1,3,5-thiadiaz- ine-2-thiones were synthesized by the reaction of isobutylamine with carbon disulfide and potassium hydroxide, followed by formaldehyde and appropriate alkyl, cycloalkyl aralkyl amines, amino acid, and INH. Their structures have been elucidated by spectral data and elemental analysis. The title compounds were tested for antimicrobial activity in vitro against gram-positive bacteria [Staphylococcus aureus,and Micrococcus leuteus], gram-negative bacteria [Serratia marcescens and Escherichia coli] and some fungi [Candida albicans, Scopulariopsis brevicalus, Geotrichum candidum, Macrophomina phaseolina, Fusarium oxysporum and Trichoderma harzianum] using agar cup diffusion method. The antimicrobial activity was found to be greatly affected by the bulkiness of the side chain and the presence of polar carboxylic group. Highest activity was obtained with compounds 4a and 4k [R= CH3, CH2-COOH]

Effect of thiadiazine derivatives on intracellular amastigotes of Leishmania amazonensis

Current therapy for leishmaniasis is not satisfactory. We describe the in vitro antiproliferative effects of new thiadiazine derivatives against Leishmania amazonensis. The compounds were found to be active against the amastigote form of the parasite, inhibiting parasite growing, from 10 to 89 percent, at a concentration of 100 ng/ml. This activity suggests that thiadiazine derivatives could be considered as potential antileishmanial compounds.

In vitro and in vivo assays of 3, 5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives against Trypanosoma cruzi

Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Anti-amastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10(4) blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice

Synthesis and antihypertensive evaluation of some phthalazines containing 1,3,4-thiadiazines and 1,3,4-thiadiazin-5-ones

Starting from methyl N2[4-methylphthalazin-1-yl]dithiocarbazinate, a number of new phthalazine derivatives containing 1, 3, 4-thiadiazine and 1, 3, 4-thiadiazin-5-one rings were prepared. The structure of the new products was confirmed by spectral analysis besides synthesis via other routes. A preliminary antihypertensive evaluation revealed that most compounds possess moderate antihypertensive activity