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Bacterial resistance has become a serious public health problem in recent years, thus encouraging the search for new antimicrobial agents. Here, we report an antimicrobial peptide (AMP), called PEPAD, which was designed based on an encrypted peptide from a Kunitz-type plant peptidase inhibitor. PEPAD was capable of rapidly inhibiting and eliminating numerous bacterial species at micromolar concentrations (from 4µM to 10 µM), with direct membrane activity. It was also observed that the peptide can act synergistically with ciprofloxacin and showed no toxicity in the G. mellonella in vivo assay. Circular dichroism assays revealed that the peptide's secondary structure adopts different scaffolds depending on the environment in which it is inserted. In lipids mimicking bacterial cell membranes, PEPAD adopts a more stable α-helical structure, which is consistent with its membrane-associated mechanism of action. When in contact with lipids mimicking mammalian cells, PEPAD adopts a disordered structure, losing its function and suggesting cellular selectivity. Therefore, these findings make PEPAD a promising candidate for future antimicrobial therapies with low toxicity to the host.

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Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an Inga laurina Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of Candida species and acted as a fungicidal agent from 2.5 to 20 µmol L-1, also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed Candida tropicalis cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against C. tropicalis. Finally, non-toxicity was reported against Galleria mellonella larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents.

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The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 µM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells.

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Antimicrobial peptides (AMPs) are promising tools for developing new antibiotics. We described the design of IKR18, an AMP designed with the aid of computational tools. IKR18 showed antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). CD studies revealed that IKR18 assumes an alpha-helical structure in the membrane-mimetic environment. The action mechanism IKR18 involves damage to the bacteria membrane, as demonstrated by Sytox green uptake. Furthermore, IKR18 displayed synergic and additive effects in combination with antibiotics ciprofloxacin and vancomycin. The peptide showed anti-biofilm activity in concentration and efficiency compared with commercial antibiotics, involving the direct death of bacteria, as confirmed by scanning electron microscopy. The anti-infective activity of IKR18 was demonstrated in the Galleria mellonella model infected with S. aureus, MRSA, and Acinetobacter baumannii. The novel bioinspired peptide, IKR18, proved to be effective in the control of bacterial infection, opening opportunities for the development of further assays, including preclinical models.

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A total of 36 ethanol extracts from different anatomical parts of 27 plant species (18 families), native to the Pantanal and Cerrado biomes in Midwest Brazil, was assessed for their effect against Aedes aegypti larvae, the vector of dengue, hemorrhagic dengue, Zika and chikungunya fevers. Only the extract obtained from seeds of Guarea kunthiana (Meliaceae) proved active (LC50 = 169.93 μg/mL). A bioassay-guided investigation of this extract led to the isolation and identification of melianodiol, a protolimonoid, as the active constituent (LC50 = 14.44 mg/mL). Meliantriol, which was also obtained from the bioactive fraction, was nevertheless devoid of any larval toxicity, even at the highest concentration tested (LC50 > 100.0 mg/mL). These results indicate that the larvicidal activity of melianodiol stems from the presence of the carbonyl moiety at C-3 in the 21,23-epoxy-21,24,25-trihydroxy-tirucall-7-ene-type skeleton. The structures of both protolimonoids were established on the basis of spectral methods (1H and 13C NMR and MS). This is the first report on the toxicity of melianodiol against Ae. aegypti larvae. Based on the results, melianodiol can be regarded as a potential candidate for use as an ecologically sound biocontrol agent for reducing the larval population of this vector.

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A total of 36 ethanol extracts from different anatomical parts of 27 plant species (18 families), native to the Pantanal and Cerrado biomes in Midwest Brazil, was assessed for their effect against Aedes aegypti larvae, the vector of dengue, hemorrhagic dengue, Zika and chikungunya fevers. Only the extract obtained from seeds of Guarea kunthiana (Meliaceae) proved active (LC50 = 169.93 µg/mL). A bioassay-guided investigation of this extract led to the isolation and identification of melianodiol, a protolimonoid, as the active constituent (LC50 = 14.44 mg/mL). Meliantriol, which was also obtained from the bioactive fraction, was nevertheless devoid of any larval toxicity, even at the highest concentration tested (LC50 > 100.0 mg/mL). These results indicate that the larvicidal activity of melianodiol stems from the presence of the carbonyl moiety at C-3 in the 21,23-epoxy-21,24,25-trihydroxy-tirucall-7-ene-type skeleton. The structures of both protolimonoids were established on the basis of spectral methods (1H and 13C NMR and MS). This is the first report on the toxicity of melianodiol against Ae. aegypti larvae. Based on the results, melianodiol can be regarded as a potential candidate for use as an ecologically sound biocontrol agent for reducing the larval population of this vector.

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OBJECTIVE: To evaluate the clinical and functional outcomes from arthroscopic repairs on small and medium-sized tears of the supraspinatus muscle tendon. METHODS: 129 cases of isolated small and medium tears of the supraspinatus muscle tendon were evaluated retrospectively. The average duration of pain was 29 months. The average joint range of motion comprised active elevation of 136°, lateral rotation of 58° and medial rotation at T12 level; and the preoperative functional UCLA score averaged 17 points. In all the cases, complete repair could be achieved. RESULTS: The average score on the UCLA functional scale in the postoperative period was 32 points. The average length of follow-up was 39 months. Seventy-five cases (58%) had excellent results and 42 (32%) had good results. The average final active elevation was 156° with an average gain of 20°, and the average final lateral rotation was 57° with an average gain of 9°. Both of these were statistically significant (P < 0.05). The patients who underwent tenotomy of the long head of the biceps (LHB), with or without tenodesis, did not present statistically inferior functional outcomes, in comparison with the patients who only underwent decompression and lesion repair (P = 1.00). Fourteen cases (10.8%) presented complications during the postoperative period. Six (4.6%) developed adhesive capsulitis and four (3.1%) presented re-rupture of the tendon, proven by means of magnetic resonance imaging. CONCLUSIONS: Arthroscopic repair of small and medium tears of the supraspinatus muscle tendon provided a functional clinical improvement, with good and excellent results in 90% of the cases.

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OBJETIVO: Avaliar os resultados clínico-funcionais das reparações artroscópicas de lesões pequenas e médias do tendão do músculo supraespinal. MÉTODOS: Foram avaliados, retrospectivamente, 129 casos de lesões isoladas pequenas ou médias do tendão do músculo supraespinal. O tempo médio de dor foi de 29 meses. A amplitude articular média era de 136º de elevação ativa, 48º de rotação lateral, rotação medial no nível T12 e a escala funcional pré-operatória da UCLA foi, em média, de 17 pontos. Em todos os casos foi possível o reparo completo da lesão. RESULTADOS: A pontuação pela escala funcional da UCLA no período pós-operatório foi, em média, de 32 pontos. O tempo médio de seguimento foi de 39 meses. Setenta e cinco casos (58%) tiveram resultados excelentes e 42 (32%), bons. A elevação ativa final teve a média de 156º, com ganho médio de 20º, e a rotação lateral final foi, em média, de 57º, com ganho médio de 9º, ambos estatisticamente significativos (P < 0,05). Os pacientes submetidos à tenotomia da cabeça longa do bíceps (CLB), com ou sem tenodese, não apresentaram resultado funcional estatisticamente inferior àqueles que foram submetidos somente à descompressão e reparo da lesão (P = 1,00). Quatorze casos (10,8%) apresentaram complicações no período pós-operatório. Seis casos (4,6%) desenvolveram capsulite adesiva e quatro (3,1%) tiveram rerruptura do tendão comprovada por ressonância magnética. CONCLUSÕES: O reparo artroscópico das lesões pequenas e médias do tendão do músculo supraespinal proporcionou melhora clínico-funcional com bons e excelentes resultados em 90% dos casos.

OBJECTIVE: To evaluate the clinical and functional outcomes from arthroscopic repairs on small and medium-sized tears of the supraspinatus muscle tendon. METHODS: 129 cases of isolated small and medium tears of the supraspinatus muscle tendon were evaluated retrospectively. The average duration of pain was 29 months. The average joint range of motion comprised active elevation of 136º, lateral rotation of 58º and medial rotation at T12 level; and the preoperative functional UCLA score averaged 17 points. In all the cases, complete repair could be achieved. RESULTS: The average score on the UCLA functional scale in the postoperative period was 32 points. The average length of follow-up was 39 months. Seventy-five cases (58%) had excellent results and 42 (32%) had good results. The average final active elevation was 156º with an average gain of 20º, and the average final lateral rotation was 57º with an average gain of 9º. Both of these were statistically significant (P < 0.05). The patients who underwent tenotomy of the long head of the biceps (LHB), with or without tenodesis, did not present statistically inferior functional outcomes, in comparison with the patients who only underwent decompression and lesion repair (P = 1.00). Fourteen cases (10.8%) presented complications during the postoperative period. Six (4.6%) developed adhesive capsulitis and four (3.1%) presented re-rupture of the tendon, proven by means of magnetic resonance imaging. CONCLUSIONS: Arthroscopic repair of small and medium tears of the supraspinatus muscle tendon provided a functional clinical improvement, with good and excellent results in 90% of the cases.

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Introdução: As fraturas supra e intercondilianas do úmero, em adultos, são lesões complexas e de difícil tratamento, pelas características anatômicas locais e pela grande fragmentação óssea que geralmente ocorre. Objetivo: Avaliar o resultado funcional do tratamento cirúrgico dessas fraturas em adultos. Método: No período de junho de 1999 a agosto de 2005, 22 pacientes (22 cotovelos) com idade entre 20 e 70 anos, com fraturas supra e intercondilianas do úmero, foram submetidos a tratamento cirúrgico mediante redução aberta e fixação interna rígida, com placas e parafusos de 3,5 mm, por via de acesso posterior. Resultados: De acordo com o critério de Jupter et al, obtivemos 68,2% de resultados classificados como satisfatórios e, como complicações do tratamento, um paciente (4,5%) apresentou neuropraxia ulnar, que regrediu espontaneamente e outros dois (9%) que apresentavam dor no olécrano, causada pelo material de síntese. Após a retirada desse material de síntese referiram melhora. Conclusões: O tratamento cirúrgico para as fraturas supra e intercondilianas do úmero mostrou ser um método eficaz com 68,2% de resultados classificados como satisfatórios neste estudo.

Introduction: The supracondylar and intercondylar humerus fractures are complex injuries of difficult treatment because of the local anatomic features and the bone fragmentation that generally occurs. Objective: To access the functional outcome of surgical treatment of these fractures in adults. Method: From June 1999 to August 2005, 22 patients (22 elbows) ranging from 20 to 70 years old who had supracondylar and intercondylar humerus fractures were submitted to surgical treatment by posterior approach with open reduction and internal fixation with 3,5 mm screws and plates. Results: According to Jupiter’s criteria, we found satisfactory results in 68.2% of the patients. One patient (4,5%) presented ulnar neuropraxia with spontaneous subsidence, and two patients (9%) who had pain caused by the tension band on the olecranon needed to have it removed and then were satisfied with the result. Conclusions: In this study, the surgical treatment for the supracondylar and intercondylar humerus fractures led to an acceptable rate of satisfactory outcomes (68,2%).

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Introdução: Descrever um padrão diferente de fratura do processo coronoide associada à instabilidade do cotovelo tratada com sucesso em nosso serviço. Relato do caso: Um paciente de 27 anos, do sexo masculino e destro, havia sofrido luxação do cotovelo. Procurou nosso hospital com uma queixa de dor e instabilidade à extensão do cotovelo, apresentando instabilidade em varo-valgo e queixa de luxação eminente do cotovelo quando este atingia -30º de extensão. No exame radiográfico, observou-se uma fratura anteromedial do processo coronoide. Submetido ao tratamento cirúrgico fixando-se a fratura, reparando-se o ligamento colateral medial, imobilizado-se com uma tala gessada por dez dias e, depois, iniciando-se o programa de reabilitação. Após 21 meses de seguimento, o paciente mantinha 135º de flexão e 0º de extensão, 80º de pronação e 90º de supinação; força muscular grau V e sem instabilidade no exame físico. As radiografias de controle demonstraram consolidação completa sem ossificação heterotópica. Discussão: Apesar de ser um tipo raro de fratura do processo coronoide, é importante que seja devidamente diagnosticado pelo ortopedista para que se realize o tratamento adequado e se evite a instabilidade crônica. O presente caso foi tratado com sucesso por meio de redução aberta e fixação interna, sem nenhuma queixa de instabilidade após 21 meses de seguimento.

Introduction: Description of a different pattern of coronoid process fracture related to elbow instability, treated successfully at our institution. Case report: A 27-year-old right-handed male suffered an elbow dislocation and attended our clinic with a complaint of pain, presenting varus and valgus instability and reporting sensation of eminent dislocation with elbow in -30º of extension. The radiographs showed an antero-medial fracture of the coronoid process. Submitted to surgical treatment with fracture fixation and ligament repair, the patient used a splint for ten days and then started the rehabilitation program. After 21 months of follow-up, the patient presented a range of motion of 135º of flexion and 0º of extension, 80º of pronation and 90º of supination; complete muscle strengh and no instability at phisical examination. The postoperative radiographs showed complete fracture consolidation without heterotopic ossification. Discussion: Even tough it is a rare fracture of the coronoid process, it is important to be diagnosed by the orthopedist to provide appropriate treatment and to avoid chronic instability. The case reported was successfully treated with open reduction and internal fixation, with no complaint of instability after 21 months of follow-up.

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