A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

Efeitos antrópicos sobre concentrações de metais alcalinos na região da microbacia do Arroio Araçá, Canoas - Rio Grande do Sul

This work presents alterations in the concentrations of alkaline metals sodium, lithium and potassium, in abiotic compartments, at Araçá stream micro-basin, located in Canoas, RS. Its spring is located in a low populational density region and crosses an elevated environmental impacted urban area. Its final course crosses an agricultural area. Samples of atmospheric particulates, macrophites, water and sediments were analyzed. High concentrations of alkaline metals, related with draining of rice fields or with the ground type, as well as correlations among its concentrations with regional activities were verified. Tripogandra diurética has shown bioaccumulation compatible with their concentrations on waters.

Ara latina

Painovuosi nimekkeestä.

Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

Doripenem was characterized through physicochemical and spectroscopic techniques, as well as thermal analysis. TLC (Rf = 0.62) and HPLC (rt = 7.4 min) were found to be adequate to identify the drug. UV and infrared spectra showed similar profile between doripenem bulk and standard. The ¹H and 13C NMR analysis revealed chemical shifts that allowed identifying the drug. Thermal analysis demonstrated three steps with mass loss, at 128, 178 and 276 ºC. The work was successfully applied to qualitative analysis of doripenem, showing the reported methods can be used for physicochemical characterization of doripenem

Valtiotieteellinen Yhdistys 75 vuotta

Juhlapuhe 24.9.2010.

Distribuição de biomassa e nutrientes na aréa de Mimosa caesalpiniaefolia Benth

O trabalho foi realizado na Estação Experimental de Itambé, PE, para avaliar a distribuição da biomassa e nutrientes em povoamentos de Mimosa caesalpiniaefolia Benth. Foram estudados dois povoamentos, em solo e topografia similares com oito e 11 anos de idade, nos espaçamentos de 3,0 x 3,0 m e 4,5 x 4,5 m, respectivamente. A biomassa foi determinada para cada componente aéreo. As amostras de folhas, galhos, cascas e fuste foram coletadas e analisadas quimicamente. A biomassa total encontrada foi de 66,22 e 80,78 t/ha, nos povoamentos I e II, respectivamente. O material lenhoso (galhos e lenho) representou 96,52 e 97,98% da biomassa total, nos povoamentos I e II. A distribuição de biomassa nos povoamentos I e II foi, respectivamente; de galhos (44,99 e 53,40%), fuste (51,53 e 44,58%), casca (2,39 e 1,40%) e folhas (1,10 e 0,62%). A ordem de concentração de nutrientes nos dois povoamentos, em todos os componentes da parte aérea, de modo geral, obedeceu à seguinte ordem decrescente: nitrogênio > cálcio > potássio > magnésio > enxofre > fósforo.

Kantatie 75 Lastukosken kohdan aluevaraussuunnitelma

Aluevaraussuunnitelma koskee Lastukosken kohtaa Siilinjärven - Nurmeksen kantatiellä 75, missä tie ylittää Vuotjärven - Syvärin välisen vesireitin. Lastukosken alueella on kaksi kapeahkoa siltaa, jyrkkä mutka, jossa on maantieliittymä, tienvarsiasutusta ja muita toimintoja, minkä vuoksi Lastukoski on poikkeuksellinen kohta kantatiellä. Nopeusrajoituksesta 60 km/h ja suppeammasta 40 km/h -nopeussuosituksesta huolimatta alue on onnettomuusaltis. UPM-Kymmene Oy on laatimassa Lastuvirran alueella ranta-asemakaavaa. Kaavaa varten on suunniteltu aluevaraus uudelle sillalle ja siihen liittyville tiejärjestelyille. Suunnitelmassa esitetään uutta Lastuvirran siltaa noin 500 metriä nykyisten siltojen pohjoispuolelle, johon on suunniteltu alikulkukorkeudeltaan vaihtoehtoisesti 8 metrin tai 4,3 metrin silta. Nykyinen kantatiesilta rajaa vesireittiä käyttävien alusten korkeuden 4,3 metriin, kun se muutoin voisi olla 8 metriä. Päätös sillan korkeudesta tehdään myöhemmissä suunnitteluvaiheissa. Kantatie 75 tulee uudelle linjalle 1,4 km matkalla. Uudelle osuudelle tulee 80 km/h -nopeusrajoitus. Syrjään jäävä nykyinen kantatie muutetaan Lastuvirran itäpuoliselta osuudelta osaksi Säyneiseen johtavaa maantietä 5701. Lastukosken länsipuolella syrjään jäävä kantatieosuus muutetaan kevyen liikenteen väyläksi, jonka kautta hoidetaan tienvarsiasutuksen ajoyhteydet. Lastukosken nykyiset sillat jäävät pelkästään kevyen liikenteen käyttöön. Korkeamman 8 metrin sillan vaihtoehdossa kantatien kanavasillan paikalle rakennetaan uusi 8 metrin alikulun mahdollistava kevyen liikenteen silta. Hankkeen kustannusarvio on 4,6 milj. € (8 m silta) tai 3,3 milj. € (4,3 m silta). Uuden tielinjan lähipiirissä ei ole asuintaloja. Meluhaitat vähenevät liikenteen siirtyessä kauemmas asutuksesta. Henkilövahinko-onnettomuuksien arvioidaan vähenevän 14 %. Lastuvirran itäpuolella tie on linjattu siten, että siitä ei ole haittaa havaitulle liito-oravareviirille. Esisuunnitelmalla ei ole suoranaisia oikeusvaikutuksia, vaan ne syntyvät tekeillä olevan ranta-asemakaavan myötä. Hanke ei sisällyELY-keskuksen toimenpideohjelmiin eikä sen toteuttamiseen ole lähivuosina rahoitusmahdollisuuksia.

Incidence of uterine post abortion infection at Hospital de Clínicas de Porto Alegre. Is prophylactic antibiotic necessary?

OBJECTIVE: To identify the incidence of pelvic infection after miscarriage undergoing uterine evacuation in a tertiary hospital in southern Brazil and to compare with the international literature.METHODS: we reviewed electronic medical records of the Hospital de Clinicas de Porto Alegre of all patients who underwent uterine evacuation for miscarriage between August 2008 and January 2012 were reviewed. We included all patients submitted to uterine curettage due to abortion and who had outpatient visits for review after the procedure. We calculated emographic and laboratory data of the study population, number needed for treatment (NNT) and number needed to harm (NNH).RESULTS: of the 857 revised electronic medical records, 377 patients were subjected to uterine evacuation for miscarriage; 55 cases were lost to follow-up, leaving 322 cases that were classified as not infected abortion on admission. The majority of the population was white (79%); HIV prevalence and positive VDRL was 0.3% and 2%, respectively. By following these 322 cases for a minimum of seven days, it was found that the incidence of post-procedure infection was 1.8% (95% CI 0.8 to 4). The NNT and NNH calculated for 42 months were 63 and 39, respectively.CONCLUSION: The incidence of post-abortion infection between August 2008 to January 2012 was 1.8% (0.8 to 4).

Mortalidade materna: 75 anos de observações em uma Maternidade Escola

OBJETIVO: avaliar as causas de todas as mortes maternas ocorridas no período de 1927 a 2001 entre 164.161 pacientes, internadas no Serviço de Obstetrícia da Universidade Federal de Juiz de Fora. MG. MÉTODOS: estudo retrospectivo das 144 mortes maternas que ocorreram na maternidade em 75 anos, com um total de 131.048 nascidos vivos, utilizando todos os prontuários de pacientes, avaliados pela história clínica e dados da certidão de óbito (não foram realizadas necropsias). Foram registrados a idade, paridade, tempo de gestação, complicações, momento e causas de morte, estabelecendo-se o índice de mortalidade materna (IMM) hospitalar por cem mil nascidos vivos. Análise estatística pelo teste do chi2 e pela técnica de amortecimento exponencial (alfa =0,05). RESULTADOS: de 1927 a 1941 o IMM foi de 1544, entre 1942 e 1956 houve redução para 314 (p<0,001) e de 1957 a 1971 decresceu para 76,4 por cem mil nascidos vivos (p<0,001). No entanto, desde 1972 tem se mantido estável (IMM=46 nos últimos 15 anos, p=0,139). As mortes maternas mais freqüentes ocorreram entre 15 e 39 anos, em nulíparas com gestação a termo, e no puerpério imediato (53%). Causas obstétricas diretas foram responsáveis por 79,3% dos casos e indiretas em 20,7%. Analisando as causas de mortes, verificou-se que no primeiro período as causas obstétricas diretas mais freqüentes em ordem decrescente, foram a infecção puerperal, eclampsia e ruptura uterina intraparto; no segundo período, foram a hemorragia pré-parto e eclampsia, e entre 1977 e 2001, as hemorragias, abortos e pré-eclampsia. A análise dos últimos 15 anos mostrou que não houve morte por pré-eclampsia/eclampsia nem infecção puerperal e as principais causas foram hemorragia periparto, aborto e obstétricas indiretas. Relacionando a mortalidade materna por tipo de parto pelo risco relativo associado à cesárea e/ou parto vaginal, verificou-se que, quando a cesárea é indicação inevitável, o risco a ela associado é menor (risco relativo = 0,6) que o de parto por via vaginal. CONCLUSÕES: apesar da redução ao longo dos 75 anos, a mortalidade materna, de 46 por 100 mil nascidos vivos, ainda é muito elevada, não havendo decréscimo significativo desde 1972, e muitas mortes são evitáveis. Hemorragias são atualmente as causas mais freqüentes de morte materna. A mortalidade materna por aborto tem aumentado de maneira alarmante e o planejamento familiar efetivo é indispensável.