71 research outputs found

    Hydrogels and nanostructures formed from ciprofloxacin–peptide conjugates

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    Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that possesses potent activity against both Gram-positive and Gram-negative bacteria and is used to treat many infections. Despite its widespread use, ciprofloxacin is associated with side effects, which might be reduced by improving its pharmacokinetic properties. The chemical structure of ciprofloxacin is the source of some of its limitations, which include: (1) Poor membrane permeability due to lipophobicity caused by the presence of polar groups; and (2) poor transportation and absorption due to poor water solubility caused by the flat aromatic structure. Previous methods for improving the pharmacokinetic properties of ciprofloxacin have involved the synthesis of conjugates. Issues related to poor membrane permeability, transportation and absorption of drugs can also be improved by employing nanocarriers and nanomaterials. Encapsulation within nanocarriers allows targeted drug delivery and reduced side effects as lower doses of the drug can be administered. Nanocarriers that can be used for this purpose include nanoparticles and hydrogels. Our research group is interested in supramolecular hydrogels as drug delivery systems. Short amphiphilic peptides are often able to form hydrogels through self-assembly. This present work describes the synthesis of a ciprofloxacin–dehydropeptide conjugate with the aim of forming hydrogels and related nanostructures to be used for the ‘self-delivery’ of antibacterial compounds. We assessed the hydrogelation ability, antibacterial activity, and pharmacokinetic properties. TEM microscopy revealed nanotubes and nanospheres. The conjugate was unable to form hydrogels alone but was able to form hydrogels as the major component of a co-gel with another peptide gelator. Although the conjugate retained antibacterial activity at 400 µM, activity diminished at lower concentrations. Thus, future work should focus on more hydrolysable pro-drug versions of the conjugate or versions where the peptide is connected at an alternate position.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019). FCT, FEDER, PORTUGAL2020, and COMPETE2020 are also acknowledged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015)

    Vertical growth control during maxillary expansion using a bonded Hyrax appliance

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    INTRODUCTION: Rapid maxillary expansion (RME) for the treatment of maxillary deficiency and posterior crossbite may induce changes in the vertical dimension. Expanders with occlusal splints have been developed to minimize unwanted vertical effects. OBJECTIVE: This preliminary study used cephalometri radiographs to evaluate the vertical effects of RME using a Hyrax appliance in children with maxillary deficiency. METHOD: Twenty-six patients (11 boys; mean age = 8 years and 5 months) with maxillary deficiency and posterior crossbite were treated using a Hyrax appliance with an acrylic occlusal splint. Radiographs and cephalometric studies were performed before the beginning of the treatment (T1) and after RME active time (T2), at a mean interval of 7 months. Results were compared with normative values. RESULTS AND CONCLUSIONS: At the end of treatment, there were no statistically significant changes, and measurements were similar to the normative values. Data showed that there were no significant effects on vertical growth, which suggests that appliances with occlusal splints may be used to correct transverse deficiencies regardless of the patient's growth pattern

    Avaliação dos gastos com o cuidado do idoso com demência

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    BACKGROUND: This is a study on the expenses borne by families that care for an elderly individual with dementia. Considering the economic impact that this condition has on family finances, the expenses incurred through caring for 41 patients have been analyzed. OBJECTIVE: To identify the expense and income structure among families that have the responsibility of caring for a demented elderly individual. METHODS: This was an exploratory, descriptive and cross-sectional study evaluating the expenses involved in caring for demented patients. A questionnaire was answered by 41 patients relatives who were responsible for their care. These patients were recruited at the neurogeriatric outpatient clinic of Open University of the Third Age, State University of Rio de Janeiro (UnATI/UERJ). RESULTS: The results suggest that there is a great impact. An average of 66% of family income was committed, with expenses that could reach 75% in the early stages of the disease, and 62% in the advanced stages. When associated with other chronic diseases, about 80% of the family income was committed. CONCLUSIONS: From the public health perspective, these findings have reiterated the conclusions from previous research, thus indicating that the increased expenses involved in care had a detrimental effect on caregivers physical and mental health. That is, the impact of the expenses can be considered to be an indicator of the degree of stress and overload, and particularly the emotional overload, that so frequently accompanies these caregivers responsibilities.CONTEXTO: Trata-se de um estudo sobre os gastos da família com o idoso com síndrome demencial. Considerando o impacto financeiro que essa condição de saúde gera, foram analisados os gastos de 41 famílias. OBJETIVO: Identificar a estrutura de gasto e receita das famílias responsáveis pelo cuidado de pacientes portadores desta condição. MÉTODOS: Trata-se de um estudo de avaliação de gastos e se caracteriza por ser exploratório, descritivo e transversal. Seu objeto envolve a unidade familiar na qual o doente se insere e os gastos relacionados ao cuidado com o idoso que tem síndrome demencial. O questionário foi aplicado a um grupo de 41 pacientes e suas famílias acompanhados no ambulatório de neurogeriatria da Universidade Aberta da Terceira Idade/Universidade do Estado do Rio de Janeiro (UnATI/UERJ). Portanto, trata-se de um estudo de caso. RESULTADOS: Os achados sugerem que a repercussão é realmente grande e chega a comprometer, em média, 66% da renda familiar com gastos que podem chegar a 75% no caso de pacientes em estágio inicial, a 62% no estágio avançado e a cerca de 80% da renda familiar, quando associada a outra doença crônica. CONCLUSÕES: Da perspectiva da saúde pública, esses achados reiteram as conclusões das pesquisas prévias que apontam ser o aumento dos gastos com o cuidado uma das dimensões que contribuem para as alterações na saúde física e mental dos cuidadores. Ou seja, o impacto dos gastos pode ser considerado um indicador do grau de estresse e sobrecarga, principalmente emocional, que tão freqüentemente acompanha as responsabilidades dos cuidadores

    The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

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    Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications

    Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

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    Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt
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