Antibacterial and Osteogenic Dual-Functional Micronano Composite Scaffold Fabricated via Melt Electrowriting and Solution Electrospinning for Bone Tissue Engineering.

The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

Aptamer-free upconversion nanoparticle/silk biosensor system for low-cost and highly sensitive detection of antibiotic residues.

The detection of antibiotics is crucial for safeguarding the environment, ensuring food safety, and promoting human health. However, developing a rapid, convenient, low-cost, and sensitive method for antibiotic detection presents significant challenges. Herein, an aptamer-free biosensor was successfully constructed using upconversion nanoparticles (UCNPs) coated with silk fibroin (SF), based on Förster resonance energy transfer (FRET) and the charge-transfer effect, for detecting roxithromycin (RXM). A synergistic FRET efficiency was achieved by utilizing alizarin red and RXM complexes as energy acceptors, with UCNP as the energy donor, and immobilizing an ultrathin SF protein corona within 10 nm. The biosensor detects RXM in deionized water with high sensitivity primarily through monolayer adsorption, with a detection range of 1.0 nM-141.6 nM and a detection limit as low as 0.68 nM. The performance of this biosensor was compared with the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for detecting antibiotics in river water separately and a strong correlation between the two methods was observed. The biosensor exhibited long-term stability in aqueous solutions (up to 60 d) with no attenuation of fluorescence intensity. Furthermore, the biosensor's applicability extended to the highly sensitive detection of other antibiotics, such as azithromycin. This study introduces a low-cost, eco-friendly, and highly sensitive method for antibiotic detection, with broad potential for future applications in environmental, healthcare, and food-related fields.

Bioadsorption, bioaccumulation and biodegradation of antibiotics by algae and their association with algal physiological state and antibiotic physicochemical properties.

Bioadsorption, bioaccumulation and biodegradation processes in algae, play an important role in the biomagnification of antibiotics, or other organic pollutants, in aquatic food chains. In this study, the bioadsorption, bioaccumulation and biodegradation of norfloxacin [NFX], sulfamethazine [SMZ] and roxithromycin [RTM]) is investigated using a series of culture experiments. Chlorella vulgaris was exposed to these antibiotics with incubation periods of 24, 72, 120 and 168 h. Results show the bioadsorption concentration of antibiotics in extracellular matter increases with increasing alkaline phosphatase activity (AKP/ALP). The bioaccumulation concentrations of NFX, SMZ and RTM within cells significantly increase after early exposure, and subsequently decrease. There is a significant positive antibiotics correlation to superoxide dismutase (SOD), the photosynthetic electron transport rate (ETR) and maximum fluorescence after dark adaptation (Fv/Fm), while showing a negative correlation to malondialdehyde (MDA). The biodegradation percentages (Pb) of NFX, SMZ and RTM range from 39.3 - 97.2, 41.3 - 90.5, and 9.3 - 99.9, respectively, and significantly increase with increasing Fv/Fm, density and chlorophyll-a. The accumulation of antibiotics in extracellular and intracellular substances of C. vulgaris is affected by antibiotic biodegradation processes associated with cell physiological state. The results succinctly explain relationships between algal growth during antibiotics exposure and the bioadsorption and bioaccumulation of these antibiotics in cell walls and cell matter. The findings draw an insightful understanding of the accumulation of antibiotics in algae and provide a scientific basis for the better utilization of algae treatment technology in antibiotic contaminated wastewaters. Under low dose exposures, the biomagnification of antibiotics in algae is affected by bioadsorption, bioaccumulation and biodegradation.

Competitive adsorption and bioaccumulation of sulfamethoxazole and roxithromycin by sediment and zebrafish (Danio rerio) during individual and combined exposure in water.

Antibiotics are extensively used for health protection and food production, causing antibiotic pollution in the aquatic environment. This study aims to determine the bioavailability and bioaccumulation of typical antibiotics sulfamethoxazole (SMX) and roxithromycin (RTM) in zebrafish under environmentally realistic conditions. Four different microcosms, i.e. water, water-sediment, water-zebrafish, and water-sediment-zebrafish were constructed, with three replicates in parallel. The concentrations of SMX and RTM in water, sediment and zebrafish were extracted and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to assess their kinetic behavior and bioavailability. In the water-sediment system, the dissolved concentration of both SMX and RTM decreased with time following the first-order kinetic while their adsorption by sediment increased with time. In the water-zebrafish system, SMX and RTM bioaccumulation was increasing with time following the pseudo second-order kinetics. RTM bioaccumulation in zebrafish (up to 16.4 ng/g) was an order of magnitude higher than SMX (up to 5.2 ng/g), likely due to RTM being more hydrophobic than SMX. In addition, the bioaccumulation factor (BAF) value of SMX in zebrafish was greater than its sediment partition coefficient, while the opposite trend was observed for RTM, demonstrating the importance of antibiotics properties in affecting their bioavailability. Furthermore, increasing dissolved organic carbon concentration in water reduced SMX bioaccumulation, but increased RTM bioaccumulation at the same time. The findings are important in future studies of environmental fate and bioavailability of toxic chemicals with different pollution sources and physicochemical properties.

Simultaneous determination of macrolides in water samples by solid-phase extraction and capillary electrophoresis.

Solid-phase extraction (SPE) coupled with capillary electrophoresis (CE) for the determination of macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, tylosin) and tiamulin in water samples was described in this article. These compounds were extracted with different types of sorbents ( Oasis HLB, C18, C8, SDB, and Strata-X) and different masses of sorbents (60 mg, 200 mg, and 500 mg) using different organic solvents (methanol, ethanol, and acetonitrile) and different pH values of water samples (pH 7.00, 8.00, and 9.00). It was found that the highest extraction efficiency of the studied compounds was obtained with 200 mg/3 mL C18 cartridges with methanol as eluent at pH 9.00 of the water sample. The developed SPE-CE method for macrolide antibiotics and tiamulin was validated for linearity, precision, repeatability, the limit of detection (LOD), the limit of quantification (LOQ), and recovery. Good linearity was obtained in the range of 0.3-30 mg L-1 depending on the drug, with correlation coefficients higher than 0.9958 in all cases except clarithromycin (0.9873). Expanded measurement uncertainties were calculated for each pharmaceutical, accounting for 20.31 % (azithromycin), 38.33 % (tiamulin), 28.95 % (clarithromycin), 26.99 % (roxithromycin), and 21.09 % (tiamulin). Uncertainties associated with precision and calibration curves contributed the most to the combined measurement uncertainty. The method was successfully applied to the analysis of production waste-water from the pharmaceutical industry.

Informe diário de evidências COVID-19: busca realizada em 20 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 20, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos.

Infecciones de transmisión sexual por Ureaplasma urealyticum y Mycoplasma hominis / Sexually-transmitted infections in Ureaplasma urealyticum and Mycoplasma hominis

Ureaplasma urealyticum y Mycoplasma hominis son bacterias anaerobias facultativas, que se asocian con la colonización e infección genital en los seres humanos adultos, aunque también pueden aislarse en individuos asintomáticos, lo que sugiere que pueden comportarse como patógenos oportunistas. El objetivo de este trabajo consistió en determinar la prevalencia de estos microorganismos en pacientes consultantes al Servicio de Enfermedades de Transmisión Sexual y Sida del Instituto Nacional de Epidemiología de la ciudad de Mar del Plata. Se realizó un estudio epidemiológico de tipo retrospectivo de 312 muestras de pacientes adultos de ambos sexos consultantes entre los años 2001 y 2006. La distribución por sexos fue 67.3% mujeres y 32.7% hombres, con edades comprendidas entre 15 y 71 años. La prevalencia de infección por Ureaplasma urealyticum fue de 51.9 % y la de Mycoplasma hominis de 25.6 %. La detección de estos microorganismos en forma simultánea para un mismo paciente fue de 30.2 %. La doxiciclina fue el antibiótico que mayor sensibilidad presentó frente a estos aislamientos. Candida albicans resultó el microorganismo más asociado a la presencia concomitante de U. urealyticum y M. hominis. De acuerdo con los datos obtenidos resulta necesario intensificar la detección de estos microorganismos potencialmente patógenos para monitorear su circulación en la población...

Incidencia, diagnóstico, manejo y evolución de las neumonías atípicas en el Hospital Militar Cap. (Av) Guillermo Hernández Jacobsen: enero 1999-mayo 2006 / Incidence, diagnosis, management and development of atypical pneumonia at the Military Hospital Cap. (Av)Guillermo Hernández Jacobsen: january 1999-may 2006

Se realiazó un estudio descriptivo, retrospectivo y observacional mediante la revisión de 35 historias médicas de pacientes hospitalizados con Neumonía Atípica entre enero de 1999 y mayo de 2006. El grupo etáreo más afectado fue el de 15 a 39 años de edad, que representa el 54.2 por ciento. Los síntomas más frecuentes fueron de origen respiratorio, como son tos (32.5 por ciento) y disnea (26.25 por ciento). El 22.8 por ciento resultó positivo para Mycoplasma y el 20 por ciento para Chlamydia. Al momento del ingreso, se manejó con amtibioticoterapia basada en Levofloxacina en un 29.7 por ciento. Claritromicina en un 16.2 por ciento. Se observo evolución satisfactoria en el 82.8 por ciento de los casos en estudio.

The effect of milk on plasmatic and tissue levels of macrolides: in vivo study in rats

The ingestion of milk with drugs, particularly some antibiotics, is frequently recommended in order to decrease possible gastrointestinal discomfort. The objective of this sutdy was to assess the interference of milk in the absorption and tissue levels of macroline antibiotics (erythromycin, clarithromycin, roxithromycin and azithromycin). Forty female rats received surgically-implanted PVC sponges on their backs. One week later, granulomatous tissue was observed and the animals were divided into eight groups, which received erythromycin, clarithromycin, roxithromycin and azithromycin with and without milk. One hour after administration of antibiotic, the animals were sacrificed. The serum and tissue samples were submitted to microbiological assay with Micrococcus luteus ATCC 9341, in order to determine drug concentration. Milk did not cause any reduction in the serum and tissue levels of azithromycin and clarithromycin (p>0.05, t-test). However, ingestion of milk reduced by approximately 28.7% the roxithromycin (p<0.0001, t-test) and by 34.1% the rythromycin (p<0.0001, t-test) serum concentrations. Similar effects were observed on tissue levels. Milk ingestion caused a reduction of approximately 20.8% in the roxithromycin (p<0.0001, t-test) and 40% in the erythromycin (p<0.0001, t-test) tissue levels. We concluded that erythromycin and roxithromycin should be not administered with milk

Efeito antiálgico da roxitromicina sobre o teste de contorçäo indusido pelo ácido acético em camundongos / Atialgic effect of roxithromycin on the acetic acid-induced writhing response in mice

No presente estudo, os autores compararam a eficácia da roxitromicina, um antimicrobiano macrolídio (20 mg/kg), com uma droga antiinflamatória, o nimesulide (4 mg/kg), na reduçäo das contorçöes evocadas pelo ácido acético em camundongos. Foram utilizados 24 animais distribuídos em 3 grupos: salina, roxitromicina e nimesulide. Os resultados obtidos mostraram que tanto o grupo tratado com nimesulide quanto o tratado com roxitromicina apresentaram uma reduçäo nas contorçöes abdominais produzidas pelo ácido acético quando comparados com a salina (P<0,001). Quando os grupos tratados foram comparados, o grupo do nimesulide apresentou maior reduçäo nas contorçöes em relaçäo ao da roxitromicina (P<0,01). Conclui-se que embora a roxitromicina possua atividade antiálgica, esta é inferior a do nimesulide quando empregada nas doses propostas

Emergencia de resistencia a macrólidos en streptococcus pyogenes / Emergence of macrolide resistant streptococcus pyogenes strains

Background: Diseases produced by Streptoccocus pyogenes are still a problem in Chile, as in the rest of the world. It exhibits in vitro susceptibility to different antimicrobials, but penicillin continues to be the treatment of choice. Alternative drugs have been developed for allergic patients, such as erythromycin, new macrolides and cephalosporins. Nevertheless, resistant strains are appearing due to the indiscriminate use of macrolides. Aim: To assess present antimicrobial susceptibility of S Pyogenes strains isolated from chilean patients. Material and Methods: The susceptibility to penicillin, macrolides, clindamycin, cephalotin and vancomycin of 153 S Pyogenes strains, obtained from different health centers of the Metropolitan Region and isolated between 1996 and 1998, was assessed using the Kirby-Bauer method. Agar dilution minimal inhibitory concentration was then determined to macrolide resistant strains. Results: All strains were susceptible to penicillin. There was a 7.2 percent cross-resistance to macrolides. Conclusions: These results confirm that S Pyogenes resistance to macrolides has increased considerably in the Metropolitan Region of Chile during the last years

Avaliaçäo da resposta clínica ao uso de antibióticos por via oral e via inalatória em pacientes portadores de bronquiectasias / Evaluation of clinical response in the antibiotics use by inhalatory and oral ways in patients with bronchiectasis

Objetivo. A base desta técnica foi obter alta concentração do antibiótico que excedia a concentração mínima inibitória (MIC) para a carga bacteriana presente no escarro. Método. Para avaliar a resposta de pacientes portadores de bronquiectasis em quadros de exacerbações infecciosas ao tratamento com antibiótico por via oral (roxitromicina 300 mg/dia por 21 dias) e nos casos de fracasso deste esquema uso de antibiótico por via inalatória (gentamicina 80 mg/2 vezes dia por 21 dias), foram avaliados em 28 pacientes atendidos noambulatório da especialidade, alguns sinais e sintomas respiratórios de acordo com a escala de Cotes modificada (secreção brônquica, tosse, broncoespasmo e dispnéia). Análise Estatística. Utilizamos o seguinte tratamento estatístico: teste de concordância Kappa e teste de McNemar para a discordância na avaliação dos graus de sinais e sintomas respiratórios, teste exato de Fischer para os efeitos colaterais apresentados, teste G de Cochran para análise dos antecedentes pessoais. Resultados. Observamos que a presença dos antecedentes pessoais não influenciaram a evolução da infecção brocopulmonar, houve melhora significante nos sinais e sintomas avaliados excetuando-se a dispnéia que permaneceu inalterada em 80 por cento dos casos. Discussão. O grupo que fez de esquema antibiótico por via inalatória após fracasso do esquema via oral foi beneficiado com período médio sem infecção brocopulmonar significantemente superior, embora a presença de efeitos colaterais tenha sido superior neste grupo, porém sem repercussão clínica. Conclusão. O controle de quadros de exacerbação infecciosa em portadores de bronquiectasias foi melhor com o antibiótico por via inalatória do que por via oral.

Thrombocytopenic purpura in a patient with macrolide-treated upper airway infection - drug related side effect or idiopathic thrombocytopenic purpura (ITP)

Os autores apresentam relato de caso de um homem de 55 anos de idade que desenvolveu púrpura trombocitopênica com sangramento da pele e membranas mucosas e macro-hematúria após infecçäo das vias aéreas superiores tratada com o macrolídeo roxitromicina. Foi feito o diagnóstico de púrpura trombocitopênica idiopática crônica com início agudo e excluído o de citopenia droga-induzida devido ao rápido início após ingestäo de apenas três comprimidos, à recuperaçäo retardada, ao curso crônico e aos dados epidemiológicos. O diagnóstico deferencial e o tratamento säo discutidos resumidamente

Bioequivalence evaluation of two roxithromycin formulations in healthy human volunteers by high performance liquid cromatography coupled to tandem mass spectrometry

The bioequivalence of two different formulations containing roxithromycin (SPE-712-1). Oral suspension 300mg/ 15mL as test formulation and Rotram©, tablets 300mg as reference formulation, both by Schering Plough S.A., Brazil) was evaluated in 24 healthy volunteers of both sexes (12 male and 12 female). The study was conducted open with randomized two-period crossover design and a 14-day washout period. Each subject received 300 mg of each roxithromycin formulation. Plasma samples were obtained over a 72-hour interval and roxithromycin concentrations were analyzed by combined LC-MS/MS with positive ion electrospray ionization using selected ion monitoring method. From the plasma roxithromycin concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(0-oo), Cmax,t1/2 ratios and tmax individual differences. The 90 percent for confidence interval (CI) of geometric mean SPE-712-L/ Rotram© individual percent ratio were 105.0-128,3 percent for AUC(0-72h), and 78.4-96.9 for Cmax. Although this 90 percent Cl were marginally outside the interval proposed by the Food and Drug Administration, the probability assessed by the two-one sided West for ratios was included in the 0.8-1.25 interval, as we concluded that SPE-712-L oral suspension formulation was bioequivalent to Rotram tablet formulation for the extent and rate of absorption.

Novos macrolídeos: roxitromicina, claritromicina e azitromicina / New macrolides: roxithromycin, clarithromycin and azithromycin

A busca contínua de um antimicrobiano ideal desperta interesse pelos macrolídeos. Alta biodisponibilidade por via oral, extensa distribuição tecidual, boa penetração intracelular e baixa incidência de reações adversas fazem dos novos macrolídeos um avanço ao encontro deste objetivo

Macrólidos / Macrolides

Se hace una revisión de este grupo de antimicrobianos, sus indicaciones actuales y espectro de actividad. Se particulariza en los nuevos macrólidos y azálides, fundamentalmente azitromicina, claritromicina y roxitromicina, sus propiedades farmacológicas, y mayor amplitud del espectro antibacteriano de estos novedosos compuestos

Estudo comparativo da eficácia e tolerabilidade da roxitromicina versus amoxilina no tratamento da amigdalite e rinofaringite bacteriana aguda / Comparative study of efficacy and tolerability od roxithromycin versus amoxicillin in the treatment of acute bacterial tonsillitis and rhiropharingitis

Foram avaliados 30 pacientes divididos em dois grupos terapêuticos com 15 pacientes cada, com intuito de estabelecer-se a eficácia e a segurança do tratamento com roxitromicina 300 mg dose única diária, por um período de cinco dias, comparado ao esquema de três administraçoes diárias de 500 mg de amoxicilina, por período de sete dias. Os sinais e os sintomas clássicos de amigdalites e rinofaringites agudas foram avaliados durante a inclusao dos pacientes e em um segundo momento que seria no oitavo dia após o início do tratamento. A análise da eficácia foi realizada através de uma avaliaçao evolutiva da variáveis envolvidas no estudo. Os resultados sobre a segurança do tratamento foram obtidos através dos registros de reaçoes adversas relatadas pelos pacientes durante o tratamento. No final do tratamento, um índice de 73,3 por cento de resoluçao completa e de 26,7 por cento de melhora foi obtido com o tratamento da roxitromicina em comparaçao a índices de 53,3 por cento e 46,7 por cento com tratamento da amoxicilina, respectivamente. Nenhum dos tratamentos resultaram em falha terapêutica.