A randomised, double-blinded trial to assess the effect of oclacitinib and prednisolone on intradermal allergen and prick tests in dogs with atopic dermatitis.

BACKGROUND: Intradermal (IDT) and prick (PT) tests are used to select allergens for allergen-specific immunotherapy in dogs with atopic dermatitis (cAD). However, the use of antipruritic drugs before performing these tests may influence the results. OBJECTIVE: To evaluate the influence of the drugs oclacitinib and prednisolone on the immediate-phase reactions of IDT and PT. ANIMALS: Thirty client-owned dogs with cAD with positive reactions to at least one allergen extract on IDT or PT. MATERIALS AND METHODS: Dogs were randomly assigned to receive oclacitinib 0.4-0.58 mg/kg per os, every 12 h (n = 14), or prednisolone 0.37-0.65 mg/kg p.o., every 12 h (n = 16) for 14 days. IDT and PT were performed on Day (D)0 before treatment and on D14. RESULTS: At D14 there was no significant reduction in the means of the orthogonal diameters of the positive immediate-phase reactions of the IDT (p = 0.064) in the oclacitinib group; however, in the PT, the diameter of the positive reactions reduced significantly (p = 0.048). In both tests, there was no significant reduction in the total number of positive reactions (IDT, p > 0.999; PT, p = 0.735). In the prednisolone group, the means of the orthogonal diameters of positive immediate-phase reactions were significantly reduced in both tests (IDT, p = 0.001; PT, p ≤ 0.001) and there also was a reduction in the total number of positive reactions (IDT, p = 0.022; PT, p = 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The use of oclacitinib 0.4-0.58 mg/kg twice daily for 14 days does not interfere with IDT results in dogs with cAD. However, oclacitinib may reduce PT reactivity. The use of prednisolone 0.37-0.65 mg/kg twice daily results in a reduction in both IDT and PT results.

Immunomodulatory Effects of Cinnamaldehyde in Staphylococcus aureus-Infected Wounds.

Cinnamaldehyde (CNM) is an essential-oil component with reported anti-infective, anti-inflammatory, and healing effects, making it an interesting compound for the treatment of wound infection. Herein, we evaluated the effects of topical administration of CNM in experimental wounds infected by Staphylococcus aureus. Swiss mice (n = 12/group) were randomly allocated into three groups (CON: animals with uninfected lesions; Sa: animals with untreated infected lesions; Sa + CNM: animals with infected wounds and treated with CNM). Excisional lesions (64 mm2) were induced at the dorsal area followed by the addition of S. aureus (80 µL of a 1.5 × 108 CFU/mL bacterial suspension). The wounds were treated with CNM (200 µg/wound/day) or vehicle (2% DMSO) for 10 days. Skin samples were taken on the 3rd or 10th treatment day for quantification of inflammatory mediators, bacterial load, immunophenotyping, and histological analysis. The treatment with CNM improved the healing process and attenuated the severity of skin lesions infected by S. aureus. These effects were associated with significant decreases in bacterial loads in CNM-treated wounds. The levels of neutrophils, TNF-α, IL-6, NO, and VEGF were decreased in the lesions treated with CNM. Taken together, these data provide further evidence of the effectiveness of CNM for the treatment of skin infections.

Cinnamaldehyde for the Treatment of Microbial Infections: Evidence Obtained from Experimental Models.

Cinnamaldehyde (CNM) is a cyclic terpene alcohol found as the major compound of essential oils from some plants of the genus Cinnamomum (Lauraceae). CNM has several reported pharmacological activities, including antimicrobial, antivirulence, antioxidant, and immunomodulatory effects. These properties make CNM an attractive lead molecule for the development of anti-infective agents. In this descriptive review, we discuss the application of CNM in experimental models of microbial infection using invertebrate and vertebrate organisms. CNM (pure or in formulations) has been successfully applied in the treatment of infections caused by a range of bacterial (such as Cronobacter sakazakii, Escherichia coli, Listeria monocytogenes, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, Streptococcus agalactiae, Vibrio cholerae) and fungal (such as Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans) pathogens. All these experimental evidence-based findings have promoted the use of cinnamaldehyde as the leading molecule for developing new anti- infective drugs.

Antimicrobial and anti-inflammatory effects of Eugenia brejoensis essential oil in mice wounds infected by Staphylococcus aureus.

Eugenia brejoensis Mazine (Myrtaceae) is source of an essential oil (EbEO) with anti-infective activities against Staphylococcus aureus. This study evaluated the antimicrobial and anti-inflammatory potentials of EbEO in S. aureus-infected skin wounds. The excisional lesions (64 mm2) were induced on Swiss mice back (6 to 8-week-old) that were allocated into 3 groups (n = 12): 1) non-infected wounds (CON); 2) wounds infected with S. aureus ATCC 6538 (Sa); 3) S. aureus-infected wounds and treated with EbEO (Sa + EbEO). The infected groups received approximately 104 CFU/wound. The animals were treated with EbEO (10 µg/wound/day) or vehicle from the 1-day post-infection (dpi) until the 10th dpi. The clinical parameters (wound area, presence of exudate, edema intensity, etc.) were daily analyzed. The levels of inflammatory mediators (cytokines, nitric oxide, VEGF) and bacterial load were measured at the cutaneous tissue at 4th dpi and 10th dpi. Topical application of EbEO accelerated wound contraction with an average contraction of 83.48 ± 11.27 % of the lesion area until 6th dpi. In this period, the rates of lesion contraction were 54.28 ± 5.57% and 34.5 ± 2.67% for CON and Sa groups, respectively. The positive effects of EbEO on wound contraction were associated with significantly (p < 0.05) reduction on bacterial load and the release of inflammatory mediators (IL-6, IL-17A, TNF-α, NO and VEGF). Taken together, these data confirm the antimicrobial potential of EbEO and provide insights into its anti-inflammatory effects, making this essential oil an interesting candidate for the development of new therapeutic alternatives for infected cutaneous wounds.

Immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by Staphylococcus aureus.

This work evaluated the immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by S. aureus. Swiss mice were divided into 3 groups (n = 12/group): non-inoculated (Control group); inoculated with S. aureus (Sa group); inoculated with S. aureus and treated with Cramoll (Sa + Cramoll group). In each animal, one lesion (64 mm2) was induced on the back and contaminated with S. aureus (~4.0 × 106 CFU/wound). The treatment with Cramoll (5 µg/animal/day) started 1-day post-infection (dpi) and extended for 10 days. Clinical parameters (wound size, inflammatory aspects, etc.) were daily recorded; while cytokines levels, bacterial load and histological aspects were determined in the cutaneous tissue at 4th dpi or 11th dpi. The mice infected with S. aureus exhibited a delay in wound contraction and the highest inflammatory scores. These effects were impaired by the treatment with Cramoll which reduced the release of key inflammatory mediators (TNF-α, NO, VEGF) and the bacterial load at wound tissue. Histological evaluations showed a restauration of skin structures in the animals treated with Cramoll. Taken together, these results provide more insights about the healing and immunomodulatory properties of Cramoll and suggest this lectin as a lead compound for treatment of wound infection.

Use of Some Asteraceae Plants for the Treatment of Wounds: From Ethnopharmacological Studies to Scientific Evidences.

Severe wounds result in large lesions and/or loss of function of the affected areas. The treatment of wounds has challenged health professionals due to its complexity, especially in patients with chronic diseases (such as diabetes), and the presence of pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Taking this into consideration, the development of new therapies for wound healing requires immediate attention. Ethnopharmacological studies performed in different countries have shown the use of several plants from the Asteraceae family as wound-healing agents. Evidences gained from the traditional medicine have opened new ways for the development of novel and more efficient therapies based on the pharmacological properties of these plants. In this article, we discuss the literature data on the use of Asteraceae plants for the treatment of wounds, based on the ethnopharmacological relevance of each plant. Special attention was given to studies showing the mechanisms of action of Asteraceae-derived compounds and clinical trials. Ageratina pichinchensis (Kunth) R.M. King and H. Rob. and Calendula officinalis L. preparations/compounds were found to show good efficacy when assessed in clinical trials of complicated wounds, including venous leg ulcers and foot ulcers of diabetic patients. The compounds silibinin [from Silybum marianum (L.) Gaertn.] and jaceosidin (from Artemisia princeps Pamp.) were identified as promising compounds for the treatment of wounds. Overall, we suggest that Asteraceae plants represent important sources of compounds that may act as new and efficient healing products.

Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities.

Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthusdrasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide.

Antimicrobial activity of Buchenavia tetraphylla against Candida albicans strains isolated from vaginal secretions.

CONTEXT: Buchenavia tetraphylla (Aubl.) RA Howard (Combretaceae: Combretoideae) is an ethnomedicinal plant with reported antifungal action. OBJECTIVE: This study evaluates the antimicrobial activity of B. tetraphylla leaf extracts against clinical isolates of Candida albicans. The morphological alterations, combinatory effects with fluconazole and the cytotoxicity of the active extract were analyzed. MATERIALS AND METHODS: Extracts were obtained using different solvents (hexane: BTHE; chloroform: BTCE; ethyl acetate: BTEE; and methanol: BTME). Antimicrobial activity was determined by the broth microdilution method using nine strains of C. albicans isolated from vaginal secretions and one standard strain (UFPEDA 1007). RESULTS: All extracts showed anti-C. albicans activity, including against the azole-resistant strains. The MIC values ranged from 156 to 2500 µg/mL for the BTHE; 156 to 1250 µg/mL for the BTCE; 625 to 1250 µg/mL for the BTME and 625 µg/mL to 2500 µg/mL for the BTEE. BTME showed the best anti-C. albicans activity. This extract demonstrated additive/synergistic interactions with fluconazole. Scanning electron microscopy analysis suggested that the BTME interferes with the cell division and development of C. albicans. BTME showed IC50 values of 981 and 3935 µg/mL, against J774 macrophages and human erythrocytes, respectively. This extract also enhanced the production of nitric oxide by J774 macrophages. DISCUSSION AND CONCLUSION: Buchenavia tetraphylla methanolic extract (BTME) is a great source of antimicrobial compounds that are able to enhance the action of fluconazole against different C. albicans strains; this action seems related to inhibition of cell division.

Antimicrobial activity of calcium hydroxide associated with anew vehicle (Triethanolamine) / Atividade antimicrobiana do hidróxido de cálcio associado à um novo veículo (Trietanolamina)

Objetivo: O objetivo deste estudo foi avaliar a capacidade antimicrobiana do hidróxido de cálcio associado à dois veículos convencionais (anestésico líquido e azeite de oliva) e um novo veículo (Trietanolamina). Material e Métodos: Inicialmente, os micro-organismos foram coletados de quatro incisivos superiores de um mesmo paciente que apresentavam tratamentos endodônticos insatisfatórios e periodontites apicais persistentes utilizando cones de papel absorvente esterilizados inseridos nos canais radiculares após a remoção do material obturador. Em seguida, estes foram cultivados em BHI durante 24 h e colocados em 10 placas de Petri com três orifícios preenchidos com as medicações avaliadas. Após 48 e 72 h, os halos de inibição foram aferidos. Resultados: Após aplicação do teste de Kruskal-Wallis com nível de significância de 1% (α = 0,01) foi observado que, hidróxido de cálcio associado à Trietanolamina, apresentou resultados semelhantes àqueles produzidos pelo líquido anestésico. Ambas as combinações foram superiores ao hidróxido de cálcio veiculado ao azeite de oliva. Conclusão: Considerando os resultados deste estudo in vitro, é possível concluir que Trietanolamina pode ser uma alternativa viável para ser utilizada como veículo associado ao hidróxido de cálcio.

Objective: The aim of this study was to evaluate the antimicrobial effectiveness of calcium hydroxide associated with a two conventional (anesthetic liquidand olive oil) and a new vehicle (Triethanolamine). Material and methods: Initially, microorganisms were collected from four upper incisors presenting unsatisfactory root canal treatments and persistent apical periodontitis from the same patient using sterile absorbent paper cones placed inside the root canal following initial access and root filling removal. Next, they were grown in a BHI culturemedium for 24 h. Afterwards, they were placed in 10 Petri dishes with 3 holes, where different formulations of the medications studied were placed. After 48 and 72 h, readings were taken of the growth inhibition halos. Results: After using Kruskal-Wallis test with significance level of 1% (α = 0.01) it was observed that, calcium hydroxide associated with Triethanolamine, produced results similar to those produced by the anesthetic liquid. Both combinations were superior to the association with olive oil. Conclusion: Considering the results of this in vitrostudy, it is possible to consider that Triethanolamine can be a viable alternative to be used as a vehicleassociated with the calcium hydroxide.

Terapia cognitiva - Aspectos historicos, filosoficos e conceituais

Uma abordagem terapeutica se desenvolve em circunstancias especificas e propicias, principalmente quando evidencias clinicas e dados cientificos forcam reformulacoes dos paradigmas existentes. A compreensao dos determinantes historicos e pressupostos filosoficos da terapia cognitiva e imprescindivel para o entendimento de seus principios teoricos e arsenal tecnico. Tenho sido extensamente pesquisada nos ultimos vinte anos, a terapia cognitiva hoje se constitui em alternativa terapeutica eficaz e indicada para uma serie de problemas humanos. O presente artigo pretende fornecer informacoes basicas e essenciais sobre a terapia cognitiva que proporcionem um primeiro contato tanto para aqueles que estejam seriamente interessados em estuda-la, quanto para aqueles que simplesmente desejem conhece-la.