Effect of focal adhesion kinase inhibition on osteoblastic cells grown on titanium with different topographies

Abstract Objective The present study aimed to investigate the participation of focal adhesion kinases (FAK) in interactions between osteoblastic cells and titanium (Ti) surfaces with three different topographies, namely, untreated (US), microstructured (MS), and nanostructured (NS). Methodology Osteoblasts harvested from the calvarial bones of 3-day-old rats were cultured on US, MS and NS discs in the presence of PF-573228 (FAK inhibitor) to evaluate osteoblastic differentiation. After 24 h, we evaluated osteoblast morphology and vinculin expression, and on day 10, the following parameters: gene expression of osteoblastic markers and integrin signaling components, FAK protein expression and alkaline phosphatase (ALP) activity. A smooth surface, porosities at the microscale level, and nanocavities were observed in US, MS, and NS, respectively. Results FAK inhibition decreased the number of filopodia in cells grown on US and MS compared with that in NS. FAK inhibition decreased the gene expression of Alp, bone sialoprotein, osteocalcin, and ALP activity in cells grown on all evaluated surfaces. FAK inhibition did not affect the gene expression of Fak, integrin alpha 1 ( Itga1 ) and integrin beta 1 ( Itgb1 ) in cells grown on MS, increased the gene expression of Fak in cells grown on NS, and increased the gene expression of Itga1 and Itgb1 in cells grown on US and NS. Moreover, FAK protein expression decreased in cells cultured on US but increased in cells cultured on MS and NS after FAK inhibition; no difference in the expression of vinculin was observed among cells grown on all surfaces. Conclusions Our data demonstrate the relevance of FAK in the interactions between osteoblastic cells and Ti surfaces regardless of surface topography. Nanotopography positively regulated FAK expression and integrin signaling pathway components during osteoblast differentiation. In this context, the development of Ti surfaces with the ability to upregulate FAK activity could positively impact the process of implant osseointegration.

Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

ABSTRACT Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays.

Prevalencia de la resistencia de Mycobacterium tuberculosis a quinolonas y fármacos inyectables en Colombia, 2012-2013 / Prevalence of Mycobacterium tuberculosis resistance to quinolones and injectables in Colombia, 2012-2013

Resumen Introducción: La tuberculosis es un problema de salud pública a nivel mundial. En 2014, la Organización Mundial de la Salud estimó que se habían presentado 9,6 millones de casos nuevos y 480.000 multirresistentes. La evaluación de la resistencia a fármacos inyectables y a quinolonas se introdujo hace pocos años, por lo cual no se conoce su prevalencia. Objetivo: Determinar la prevalencia de la resistencia a amicacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas, entre 2012 y 2013. Materiales y métodos: Se hizo un estudio de corte transversal con 489 aislamientos resistentes a isoniacida o rifampicina. Las pruebas de sensibilidad se hicieron con la técnica Bactec MGITTM. Para el análisis de la proporción de la resistencia, los casos se agruparon según el antecedente de tratamiento con medicamentos de segunda línea. Resultados: En los 438 casos nuevos, la resistencia global a la kanamicina fue mayor (7,1 %; IC95% 4,6-9,6); en los 51 casos previamente tratados, dicha resistencia fue de 27,5 % (IC95% 14,2-40,7). La resistencia global fue mayor en casos con antecedentes de tratamiento con quinolonas y fármacos inyectables. Se encontraron siete casos de tuberculosis extremadamente resistente. Conclusión: El estudio evidenció la presencia de resistencia a fármacos de segunda línea en personas con tuberculosis farmacorresistente sin tratamiento previo o tratadas previamente con quinolonas o fármacos inyectables, estos últimos con mayor porcentaje de resistencia. En consecuencia, es esencial practicar rutinariamente las pruebas de sensibilidad y el análisis de esta información.

Abstract Introduction: Tuberculosis is a health problem worldwide. The World Health Organization estimated 9.6 million new cases and 480,000 multirresistant cases for 2014. The assessment of resistance to quinolones and injectables was implemented only a few years ago, so its prevalence is not known. Objective: To determine the prevalence of resistance to amikacin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid and/or rifampin during 2012-2013. Materials and methods: This was a cross-sectional study of 489 isolates resistant to isoniazid and/or rifampin. We used the Bactec MGITTM technique for susceptibility tests. For analyzing the rate of resistance, we grouped cases according to the history of treatment with second line drugs. Results: In the 438 new cases, the drug that showed greater overall resistance was kanamycin with 7.1 % (95% CI: 4.6 to 9.6). In 51 previously treated cases, this highest resistance was 27.5 % (95% CI: 14.2 to 40.7). The overall resistance was higher in cases with a history of treatment with quinolones and injectables. We found seven cases of extremely resistant tuberculosis. Conclusion: This study demonstrates the presence of resistance to second line drugs in people with drug-resistant tuberculosis with and without previous treatment with quinolones and/or injectables, these latter having a higher percentage of resistance. For that reason, it is essential to perform susceptibility testing and analyze this information routinely.

Risk factors associated with structural postural changes in the spinal column of children and adolescents / Fatores de risco associados a alterações posturais estruturais da coluna vertebral em crianças e adolescentes

OBJECTIVE: To investigate the association between behavioral risk factors, specifically postural habits, with the presence of structural changes in the spinal column of children and adolescents. METHODS: 59 students were evaluated through the self-reporting Back Pain and Body Posture Evaluation Instrument and spinal panoramic radiographic examination. Spine curvatures were classified based on Cobb angles, as normal or altered in the saggital plane and as normal or scoliotic in the frontal plane. Data were analyzed using SPSS 18.0, based on descriptive statistics and chi-square association test (a=0,05). RESULTS: The prevalence of postural changes was 79.7% (n=47), of which 47.5% (n=28) showed frontal plane changes and 61% (n=36) sagital plane changes. Significant association was found between the presence of thoracic kyphosis and female gender, practice of physical exercises only once or twice a week, sleep time greater than 10 hours, inadequate postures when sitting on a seat and sitting down to write, and how school supplies are carried. Lumbar lordosis was associated with the inadequate way of carrying the school backpack (asymmetric); and scoliosis was associated wuth the practice of competitive sports and sleep time greater than 10 hours. CONCLUSIONS: Lifestyle may be associated with postural changes. It is important to develop health policies in order to reduce the prevalence of postural changes, by decreasing the associated risk factors. .

OBJETIVO: Verificar se existe associação de fatores de risco comportamentais, especificamente hábitos posturais, com a presença de alteração postural estrutural na coluna vertebral de crianças e adolescentes. MÉTODOS: Foram avaliados 59 crianças e adolescentes, que responderam ao questionário auto-aplicável Back Pain and Body Posture Evaluation Instrument e fizeram o exame radiográfico panorâmico da coluna vertebral. De acordo com o ângulo de Cobb, as curvaturas sagitais da coluna vertebral foram classificadas como normais ou alteradas e, no plano frontal, como escolioses ou normais. Os dados foram analisados no SPSS 18.0, a partir de estatística descritiva e do teste de associação qui-quadrado (a=0,05). RESULTADOS: A prevalência de alterações posturais foi de 79,7% (n=47), 47,5% (n=28) apresentavam alteração no plano frontal e 61% (n=36) no sagital. Foi encontrada associação entre cifose torácica e sexo feminino, prática de exercício físico apenas uma ou duas vezes na semana, tempo de sono superior a 10 horas, posturas inadequadas para sentar no banco e sentar para escrever e o meio de transporte do material escolar. Para lordose lombar, observou-se associação com o transporte da mochila escolar de modo inadequado (assimétrico). Houve associação significativa entre a presença de escoliose com a prática de esporte competitivo e o tempo de sono superior a 10 horas. CONCLUSÕES: Hábitos de vida podem estar associados a alterações posturais, é importante o desenvolvimento políticas de saúde a fim de reduzir a prevalência de alterações posturais por meio da redução dos fatores de risco associados. .

Quinolones: recent structural and clinical developments

Quinolones are a very important family of antibacterial agents that are widely prescribed for the treatment of infections in humans. Since their discovery in the early 1960s, the quinolone group of antibacterials has generated considerable clinical and scientific interest. Two major groups of compounds have been developed from the basic molecule: quinolones and naphthyridones. The 4-pyridone-3-carboxylic acid associated with a 5, 6-fused aromatic ring is the common chemical feature of bactericidal quinolones. In the resulting bicyclic ring, the 1-, 5-, 6-, 7-, and 8-positions are the major targets of chemical variation. Manipulations of the basic molecule, including replacing hydrogen with fluorine at position 6, substituting a cyclic amine residue at position 7 and adding new residues at position 1 of the quinolone ring, have led to improved breadth and potency of antibacterial activity and pharmacokinetics. One of the most significant developments has been the improved anti-Gram-positive activity of the newer compounds, such as moxifloxacin and garenoxacin. However, some of these structural changes have been found to correlate with specific adverse effects: the addition of fluorine or chlorine at position 8 being associated with photoreactivity, e.g. sparfloxacin; and the substitution of an amine or a methyl group at position 5 having a potential role in QTc prolongation, e.g. sparfloxacin and grepafloxacin. The clinical utility of this expanding class of antimicrobial agents, and the lower propensity for the development of resistance with the newer quinolones will need to be continually monitored in the changing therapeutic environment. Antibiotic drug choice will remain difficult in the presence of increasing resistance, but introduction of the new quinolones has created a new and exciting era in antimicrobial chemotherapy

Quinolonas: aspectos generales sobre su estructura y clasificación / Quinolones: general characteristics of structure and classification

Las quinolonas constituyen uno de los grupos de antimicrobianos de mayor desarrollo. Químicamente son estructuras bicíclicas heteroaromáticas, constituidas por un núcleo piridona- ß-ácido carboxílico y un anillo aromático. La relación entre la estructura química y la actividad biológica (relación estructura-actividad) de estas moléculas ha motivado la síntesis de compuestos con distintos radicales en la estructura química básica. Posición 1: el sustituyente de mayor importancia es el grupo ciclopropil que combina favorables propiedades estéricas, espaciales y de interacción electrónica exhibiendo las quinolonas que poseen este grupo una potente actividad sobre bacilos Gram negativos; otros sustituyentes de importante desarrollo son los anillos bencénico mono o difluorados, que amplían el espectro de actividad y mejoran las propiedades farmacocinéticas, pero podrían estar asociadas a fenómenos de toxicidad. Las posiciones 2, 3, 4 no presentan mayores variaciones. La posición 6 prácticamente define, por la presencia de flúor, a las modernas quinolonas, sin embargo, se han sintetizado quinolonas experimentales sin flúor que presentan una interesante actividad in vitro. Posición 5, la presencia de grupos amino o metilo favorece algunas propiedades farmacocinéticas. Posición 8: la presencia de halógenos aumenta la actividad antianaerobia, en particular Cl y F, pero se asocia a fenómenos de fototoxicidad incentivando la síntesis de compuestos sin halógenos. También estas moléculas se clasifican en generaciones de acuerdo al momento de su síntesis y los radicales utilizados

Esparfloxacino e as fluorquinolonas: uma revisäo de sua classificaçäo, atividade antibacteriana, mecanismo de açäo, características farmacocinéticas, tolerabilidade e perspectivas farmacêuticas / Sparfloxacin and the fluoroquinolones: a review of classification, antibacterial activity, mechanism of action, pharmacokinetic properties, tolerability and pharmaceutical perspectives

Foi realizada uma revisäo na literatura sobre as quinolonas, classe antibacteriana que possui amplo espectro de açäo, enfocando, principalmente, o esparfloxacino, fluorquinolona de terceira geraçäo que possui potente atividade contra bactérias Gram-positivas, como Streptococcus pneumoniae e Staphylococcus aureus inclusive cepas metilina resistentes (MRSA), bactérias Gram-negativas, anaeróbios, Legionella spp, Mycoplasma spp, Chlamydia spp e Mycobacterium spp.

Farmacología de las nuevas fluoroquinolonas y su utilidad en el manejo de infecciones / Pharmacology of new fluroquinolonas and its the handling of infections

Analiza que las nuevas fluoroquinolonas tienen un potente alcance sobre las bacterias Grampositivas y Gramnegativas, excelente penetración tisular, conveniente dosificación oral de una a dos veces diarias, y la Sparfloxacina y Levofloxacina parecen tener mayor efectividad que las antiguas quinolonas contra el pneumococo. Desafortunadamente, las reacciones de fotosensibilidad y otras reacciones adversas, han sido reportadas y ninguna es recomendada para ser empleada en niños, jóvenes menores de dieciocho años, mujeres embarazadas o lactantes, todo ello apoyado en estudios efectuados con animales. Sin embargo, estos efectos no ha sido claramente dilucidados. Pero en muchos casos, estos fármacos tienen un indiscriminado o inapropiado uso y ello requiere conocimiento para el adecuado manejo de las infecciones nosocomiales o de las adquiridas en la comunidad.

Quinolonas / Quinolones

Os agentes antimicrobianos estäo entre os medicamentos prescritos com maior frequência e, a cada dia, aumentam em número e complexidade, tornando-se cada vez mais difícil, até mesmo para os especialistas em doenças infecciosas, a manutençäo de conhecimentos atualizados nesta área. Os autores fazem uma revisäo sobre os anticrobianos sintéticos do grupo das quinolonas, procurando abordar alguns aspectos práticos de seu uso na prática médica diária.