RESUMO
Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was ß-glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals.
Assuntos
Modelos Animais de Doenças , Sepse , Animais , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/terapia , Humanos , Camundongos , Glucanos/uso terapêutico , Glucanos/farmacologia , beta-Glucanas/uso terapêutico , Imunomodulação/efeitos dos fármacosRESUMO
Left ventricular hypertrophy is a risk factor for cardiovascular mortality in patients on peritoneal dialysis (PD). Because icodextrin has a greater ultrafiltration power compared with glucose-based solutions for long dwell, it could improve left ventricular mass by reducing fluid overload. This was a randomized clinical trial that included patients on PD recruited from 2 teaching hospitals, in Sao Paulo-Brazil. Patients were allocated to the control glucose group (GLU) or the intervention icodextrin (ICO) group. Clinical and cardiac magnetic resonance image (MRI) parameters were evaluated at baseline and 6 months after randomization. The primary outcome was the change in left ventricular mass adjusted by surface area (ΔLVMI), measured by cardiac MRI. A total of 22 patients completed the study (GLU, N = 12 and ICO, N = 10). Baseline characteristics such as age, sex, underlying disease, and time on dialysis were similar in both groups. At baseline, 17 patients (77.3%) presented with left ventricular hypertrophy with no difference between groups (p = 0.748). According to the total body water (TBW)/extracellular water (ECW) ratio, 36.8% and 80% of patients from GLU and ICO groups, respectively, were considered hypervolemic (p = 0.044). During follow-up, ΔLVMI was 3.9 g/m (- 10.7, 2.2) in GLU and 5.2 (- 26.8, 16.8) in ICO group (p = 0.651). ΔLVMI correlated with change in brain natriuretic peptide (r = 0.566, p = 0.044), which remained significant in a multiple regression analysis. The use of the icodextrin-based solution in prevalent patients on PD compared with a glucose-based solution was not able to improve LMV. A larger randomized trial with a longer follow-up period may be needed to show changes in LVM in this patient population.Trial registration: this study has been registered at ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification #RBR-2mzhmj2, available at: https://ensaiosclinicos.gov.br/pesquisador .
Assuntos
Soluções para Diálise , Icodextrina , Diálise Peritoneal , Brasil , Glucanos/uso terapêutico , Glucose/efeitos adversos , Glucose/uso terapêutico , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Icodextrina/uso terapêutico , Peptídeo Natriurético Encefálico , Diálise Peritoneal/métodos , Estudos Prospectivos , Diálise RenalRESUMO
Several biological activities of the fungal exopolysaccharide (1 â 3)(1 â 6)-ß-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal ß-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal ß-glucan a new possibility for complementary treating acute and chronic inflammation.
Assuntos
Hiperalgesia , beta-Glucanas , Administração Oral , Produtos da Oxidação Avançada de Proteínas/metabolismo , Animais , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Glucanos/efeitos adversos , Glucanos/farmacologia , Glucanos/uso terapêutico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-10 , Leucócitos/patologia , Camundongos , Nociceptividade , beta-Glucanas/efeitos adversos , beta-Glucanas/farmacologia , beta-Glucanas/uso terapêuticoRESUMO
Breast cancer is the most common cancer worldwide among the female population. The fungal exopolysaccharide botryosphaeran is a (1â3)(1â6)-ß-D-glucan with limited solubility in water that can be promoted through carboxymethylation. Thus, the aim of this study was to examine in-vitro anticancer effects of carboxymethylated-botryosphaeran (CM-BOT) on breast cancer MCF-7 cells cultivated in multicellular tumor spheroids (MCTS). CM-BOT (≥ 600 µ/ml) decreased the viability (resazurin assay) of MCF-7 grown in monolayers after 24 hr incubation. Although CM-BOT did not markedly alter viability of MCTS in the resazurin assay after 24, 48 or 72 hr, CM-BOT ≥ 600 µg/ml produced cell-death by apoptosis after 72 hr utilizing the triple staining assay and labeling dead cells with propidium iodide, which can also be visualized on the architecture of MCTS. CM-BOT (1000 µg/ml) inhibited cell proliferation, which resulted in MCTSs with smaller diameters than controls. CM-BOT at all concentrations examined decreased the ability of MCF-7 to form colonies and to migrate in the extracellular matrix. This is the first report using MCTS-architecture to study anti-tumor effects of ß-glucans. Our findings are important in the search for compounds for use in breast cancer therapy, or as adjuvants in reducing the adverse effects of mammary tumor chemotherapy.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Feminino , Glucanos/farmacologia , Glucanos/uso terapêutico , Humanos , Células MCF-7 , Esferoides CelularesRESUMO
Constipation is a frequent problem in children. We evaluated the effect of a mixture (polydextrose [PDX] and fructooligosaccharide [FOS]) in children with constipation. We performed a prospective interventional study with a mixture (PDX 4.17 g and FOS 0.45 g) in a daily dose of food supplement. The intervention lasted 45 days, with visits at 15, 30, and 45 days after administration. The sample comprised 105 patients, of whom 77 completed the intervention. A statistically significant reduction in the frequency of symptoms was observed at the end of the study. The frequency of children with fewer than three bowel movements per week dropped from 59.7% to 11.7%, and there was a decrease in the frequency of Bristol type 1 and 2 dry stools (68.8% to 7.8%), pain on defecation (79.2% to 10.4%), and fear of defecation (68.8% to 3.9%). The proportion of children with abdominal pain symptoms decreased from 84.2% to 2.6% at the end of the study. A relevant limitation of the present study was the lack of a control group treated with placebo. The administration of the PDX/FOS mixture was accompanied by a significant reduction in the frequency of constipation symptoms of the children evaluated. The tolerability was very good, and the rate of adverse effects was low.
Assuntos
Constipação Intestinal/dietoterapia , Suplementos Nutricionais , Glucanos/uso terapêutico , Oligossacarídeos/uso terapêutico , Criança , Pré-Escolar , Fibras na Dieta/administração & dosagem , Fibras na Dieta/uso terapêutico , Quimioterapia Combinada , Feminino , Glucanos/administração & dosagem , Humanos , Masculino , Oligossacarídeos/administração & dosagemRESUMO
In recent years, orally disintegrating films (ODFs) have been studied as alternative ways for drug administration. They can easily be applied into the mouth and quickly disintegrate, releasing the drug with no need of water ingestion and enabling absorption through the oral mucosa. The ODFs matrices are typically composed of hydrophilic polymers, in which the natural polymers are highlighted since they are polymers extracted from natural sources, non-toxic, biocompatible, biodegradable, and have favorable properties for this application. Besides that, natural polymers such as polysaccharides and proteins can be applied either alone or blended with other synthetic, semi-synthetic, or natural polymers to achieve better mechanical and mucoadhesive properties and fast disintegration. In this review, we analyzed ODFs developed using natural polymers or blends involving natural polymers, such as maltodextrin, pullulan, starch, gelatin, collagen, alginate, chitosan, pectin, and others, to overview the recent publications and discuss how natural polymers can influence ODFs properties.
Assuntos
Portadores de Fármacos , Glucanos , Membranas Artificiais , Polissacarídeos , Amido , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Glucanos/química , Glucanos/uso terapêutico , Humanos , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Amido/química , Amido/uso terapêuticoRESUMO
ABSTRACT Introduction: Durasphere® EXP (DEXP) is a compound of biocompatible and non--biodegradable particles of zirconium oxide covered with pyrolytic carbon. The aim of this study is to evaluate the durability of off-label use of DEXP in the treatment of primary vesicoureteral reflux in children. Materials and Methods: Patients who underwent subureteric injection of DEXP for the correction of primary VUR were retrospectively reviewed. Patients aged >18 years as well as those who had grade-I or -V VUR, anatomic abnormalities (duplicated system, hutch diverticulum), neurogenic bladder or treatment refractory voiding dysfunction were excluded. Radiologic success was defined as the resolution of VUR at the 3rd month control. Success was radiographically evaluated at the end of the first year. Results: Thirty-eight patients (9 boys, 29 girls; mean age, 6.3±2.7 years) formed the study cohort. Forty-six renal units received DEXP (grade II: 22; grade III: 18; grade IV: 6). Mean volume per ureteric orifice to obtain the mound was 0.70±0.16mL. First con- trol VCUG was done after 3 months in all patients. After the first VCUG, 6 patients had VUR recurrence. Short-term radiologic success of DEXP was 84.2%. Rate of radiologic success at the end of the first year was 69.4% (25/32). Lower age (p:0.006) and lower amount of injected material (p:0.05) were associated with higher success rates at the end of 1 year. Conclusion: This is the first study to assess the outcomes of DEXP for treatment of primary VUR in children. After 1 year of follow-up, DEXP had a 69.4% success rate.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Refluxo Vesicoureteral/tratamento farmacológico , Zircônio/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Glucanos/uso terapêutico , Recidiva , Refluxo Vesicoureteral/cirurgia , Índice de Gravidade de Doença , Reprodutibilidade dos Testes , Estudos Retrospectivos , Dextranos/uso terapêutico , Resultado do Tratamento , Estatísticas não Paramétricas , Endoscopia/métodos , Ácido Hialurônico/uso terapêutico , InjeçõesRESUMO
INTRODUCTION: Durasphere® EXP (DEXP) is a compound of biocompatible and non-biodegradable particles of zirconium oxide covered with pyrolytic carbon. The aim of this study is to evaluate the durability of off-label use of DEXP in the treatment of primary vesicoureteral reflux in children. MATERIALS AND METHODS: Patients who underwent subureteric injection of DEXP for the correction of primary VUR were retrospectively reviewed . Patients aged >18 years as well as those who had grade-I or -V VUR, anatomic abnormalities (duplicated system, hutch diverticulum), neurogenic bladder or treatment refractory voiding dysfunction were excluded. Radiologic success was defined as the resolution of VUR at the 3rd month control. Success was radiographically evaluated at the end of the first year. RESULTS: Thirty-eight patients (9 boys, 29 girls; mean age, 6.3±2.7 years) formed the study cohort. Forty-six renal units received DEXP (grade II: 22; grade III: 18; grade IV: 6). Mean volume per ureteric orifice to obtain the mound was 0.70±0.16mL. First control VCUG was done after 3 months in all patients. After the first VCUG, 6 patients had VUR recurrence. Short-term radiologic success of DEXP was 84.2%. Rate of radiologic success at the end of the first year was 69.4% (25/32). Lower age (p:0.006) and lower amount of injected material (p:0.05) were associated with higher success rates at the end of 1 year. CONCLUSION: This is the first study to assess the outcomes of DEXP for treatment of primary VUR in children. After 1 year of follow-up, DEXP had a 69.4% success rate.
Assuntos
Materiais Biocompatíveis/uso terapêutico , Glucanos/uso terapêutico , Refluxo Vesicoureteral/tratamento farmacológico , Zircônio/uso terapêutico , Criança , Pré-Escolar , Dextranos/uso terapêutico , Endoscopia/métodos , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Injeções , Masculino , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do Tratamento , Refluxo Vesicoureteral/cirurgiaRESUMO
Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.
Assuntos
Antifúngicos/administração & dosagem , Glucanos/administração & dosagem , Imidazóis/administração & dosagem , Irritantes/administração & dosagem , Nanopartículas/administração & dosagem , Adesividade , Animais , Antifúngicos/química , Antifúngicos/uso terapêutico , Antifúngicos/toxicidade , Candida albicans/efeitos dos fármacos , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Glucanos/química , Glucanos/uso terapêutico , Glucanos/toxicidade , Humanos , Imidazóis/química , Imidazóis/uso terapêutico , Imidazóis/toxicidade , Irritantes/química , Irritantes/uso terapêutico , Irritantes/toxicidade , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/toxicidade , Onicomicose/tratamento farmacológico , Trichophyton/efeitos dos fármacosRESUMO
D-Glucans have triggered increasing interest in commercial applications in the chemical and pharmaceutical sectors because of their technological properties and biological activities. The glucans are foremost among the polysaccharide groups produced by microorganisms with demonstrated activity in stimulating the immune system, and have potential in treating human disease conditions. Chemical alterations in the structure of D-glucans through derivatization (sulfonylation, carboxymethylation, phosphorylation, acetylation) contributes to their increased solubility that, in turn, can alter their biological activities such as antioxidation and anticoagulation. This review surveys and cites the latest advances on the biological and technological potential of D-glucans following chemical modifications through sulfonylation, carboxymethylation, phosphorylation or acetylation, and discusses the findings of their activities. Several studies suggest that chemically modified d-glucans have potentiated biological activity as anticoagulants, antitumors, antioxidants, and antivirals. This review shows that in-depth future studies on chemically modified glucans with amplified biological effects will be relevant in the biotechnological field because of their potential to prevent and treat numerous human disease conditions and their clinical complications.