RESUMO
Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen's d = .51), morphology (p = 0.001 Cohen's d = .93) and motility parameters (p = 0.002 Cohen's d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed. The trial has been registered in the Iranian Registry of Clinical Trials (Registration number: IRCT20171209037794N1.
Assuntos
Antioxidantes/uso terapêutico , Fabaceae , Fármacos para a Fertilidade Masculina/uso terapêutico , Galactanos/uso terapêutico , Hormônios/sangue , Infertilidade Masculina/tratamento farmacológico , Mananas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Gomas Vegetais/uso terapêutico , Espermatozoides/efeitos dos fármacos , Vitamina E/uso terapêutico , Adulto , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Fabaceae/química , Feminino , Fármacos para a Fertilidade Masculina/efeitos adversos , Fármacos para a Fertilidade Masculina/isolamento & purificação , Hormônio Foliculoestimulante Humano/sangue , Galactanos/efeitos adversos , Galactanos/isolamento & purificação , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/diagnóstico , Irã (Geográfico) , Hormônio Luteinizante/sangue , Masculino , Mananas/efeitos adversos , Mananas/isolamento & purificação , Gomas Vegetais/efeitos adversos , Gomas Vegetais/isolamento & purificação , Gravidez , Taxa de Gravidez , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento , Vitamina E/efeitos adversosRESUMO
BACKGROUND: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. METHODS: Mice received 100 µg/25 µL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. RESULTS: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. CONCLUSION: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.
Assuntos
Ácido Hialurônico/análogos & derivados , Mananas/efeitos adversos , Exacerbação dos Sintomas , Sinovite/etiologia , Viscossuplementos/efeitos adversos , Doença Aguda , Animais , Artralgia/diagnóstico , Movimento Celular , Quimiocina CXCL1/metabolismo , Feminino , Galactose/análogos & derivados , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Injeções Intra-Articulares , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Camundongos , Líquido Sinovial , Sinovite/metabolismo , Sinovite/patologia , Viscossuplementos/administração & dosagemRESUMO
In the present study, a glucogalactomanan polysaccharide isolated from Agaricus bisporus named as TJ3 was investigated its immunomodulatory effects and molecular mechanisms in RAW 264.7 cells. Functional analysis showed TJ3 could inhibit the proliferation of RAW 264.7 cells in a certain concentration range. Moreover, TJ3 treatment increased the expression of inducible nitric oxide synthase (iNOS), which was responsible for increasing nitric oxide (NO) production. TJ3 also increased the expression of cyclooxygenase-2 (COX-2) and the mRNA levels of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and COX-2 in RAW 264.7 cells. In addition, further elucidation of molecular mechanisms showed that ERK/MAPK and IκB/NFκB pathways were activated by TJ3 treatment via increased phosphorylation levels of ERK1/2 and IκB-α, respectively. These findings indicated that TJ3 had a huge promising immunostimulatory activity and its induced immune responses probably through stimulating the ERK/MAPK and IκB/NFκB pathways. Our results demonstrate that TJ3 may be used as a potent immune modulator.
Assuntos
Agaricus/química , Polissacarídeos Fúngicos/efeitos adversos , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Mananas/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular , Polissacarídeos Fúngicos/química , Galactose/análogos & derivados , Proteínas I-kappa B/metabolismo , Imunomodulação/efeitos dos fármacos , Inflamação/etiologia , Macrófagos/imunologia , Mananas/química , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Prostaglandina-Endoperóxido Sintases/metabolismo , Células RAW 264.7RESUMO
Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber and is used in solid and liquid food to regulate gut function. The aim of this study was to investigate effects of PHGG on bowel movements (stool form and frequency), plasma bile acids, quality of life, and gut microbiota of healthy volunteers with a tendency toward diarrhea, i.e., irritable bowel syndrome diarrhea (IBS-D)-like symptoms. A randomized, double-blind, placebo-controlled, and parallel trial was performed on 44 healthy volunteers (22 males, 22 females, 41.9 ± 6.3 years old (average ± SD)) with minimum 7 bowel movements every week, wherein above 50% of their stool was between the Bristol stool scale (BSS) value of 5 and 6. Intake of the PHGG for 3 months significantly improved stool form, evaluated using BSS, and had no effects on stool frequency. BSS was significantly normalized in the group consuming the PHGG compared with the placebo. Comprehensive fecal microbiome analysis by the 16S rRNA-sequence method detected significant changes in the ratio of some bacteria, such as an increase of Bifidobacterium (p < 0.05) in the PHGG group. Our results suggest that intake of PHGG improves human stool form via regulating intestinal microbiota.
Assuntos
Bactérias/crescimento & desenvolvimento , Defecação , Diarreia/terapia , Fibras na Dieta/administração & dosagem , Fezes/microbiologia , Galactanos/administração & dosagem , Microbioma Gastrointestinal , Mananas/administração & dosagem , Gomas Vegetais/administração & dosagem , Prebióticos/administração & dosagem , Adulto , Bactérias/classificação , Bactérias/genética , Ácidos e Sais Biliares/sangue , Diarreia/diagnóstico , Diarreia/microbiologia , Diarreia/fisiopatologia , Fibras na Dieta/efeitos adversos , Método Duplo-Cego , Feminino , Galactanos/efeitos adversos , Humanos , Hidrólise , Masculino , Mananas/efeitos adversos , Pessoa de Meia-Idade , Gomas Vegetais/efeitos adversos , Prebióticos/efeitos adversos , Qualidade de Vida , Fatores de Tempo , Tóquio , Resultado do Tratamento , Adulto JovemRESUMO
BTI320 is a proprietary fractionated mannan polysaccharide being studied for attenuation of postprandial glucose excursion. The apparent blood glucose-lowering effect of this compound is effective in lowering postprandial hyperinsulinemia, participating in the metabolic regulation of other lipid molecules; the consequence of this activity is yet to be validated with BTI320 with respect to the risk of cardiovascular disease. The primary objective of the study was to determine the postprandial glucose and insulin responses to 3 test meals containing rice alone or consumed with BTI320 (study A) or 3 test meals (SpriteTM ) alone or consumed with BTI320 (study B). Twenty overweight but otherwise healthy volunteers, 4 female and 6 male (mean age 29 years, BMI 27-28 kg/m2 ) in study A and 6 female and 4 male (mean age 32 years, BMI 25-32 kg/m2 ) in study B participated in the BTI320 evaluations. Standardized postprandial response methodology was utilized. In study A the addition of 6- and 12-g BTI320 tablets reduced postprandial glucose responses to white rice by 19% and 32% and reduced postprandial insulin responses by 16% and 24%, respectively (P ≤ .05). In study B 2.6 and 5.2 g BTI320 reduced the glycemic index by 10% and 14%, respectively, and led to 14% and 18% decreases in the insulinemic index of the soft drink (P ≤ .05). These 2 studies demonstrated that the consumption of BTI320 before carbohydrate food or sugary beverage significantly reduced postprandial glucose levels and insulin responses to that meal or beverage in a dose-dependent manner.
Assuntos
Glicemia/análise , Carboidratos da Dieta/administração & dosagem , Insulina/sangue , Mananas/farmacologia , Sobrepeso/sangue , Adulto , Idoso , Área Sob a Curva , Índice de Massa Corporal , Estudos Cross-Over , Suplementos Nutricionais , Feminino , Índice Glicêmico , Voluntários Saudáveis , Humanos , Masculino , Mananas/efeitos adversos , Mananas/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Período Pós-Prandial , Estudos Prospectivos , ComprimidosRESUMO
BACKGROUND: Galactomannan(s) are plant-derived fiber shown to reduce post-prandial blood glucose by delaying intestinal absorption of carbohydrates and slowing down gastric emptying. We examined glucose-lowering effects of BTI320, a propriety fractionated mannan(s) administered as a chewable tablet before meal in a proof-of-concept study in Chinese subjects with prediabetes. METHODS: Sixty Chinese adults aged 18-70 years with either impaired fasting glucose, impaired glucose tolerance, or glycated haemoglobin 5.7-6.4% (39-46 mmol/mol), were randomly assigned in 2:2:1 ratio to either BTI320 8 g (high dose), BTI320 4 g (low dose) or matching-placebo three times daily before meal for 16 weeks. The primary endpoint was change in fructosamine in subjects treated with BTI320 compared with placebo from baseline to week 4. Indices of glycaemic variability based on continuous glucose monitoring (CGM) and standard meal tolerance test were explored in secondary analyses. RESULTS: Of 60 subjects randomized, 3 subjects discontinued study treatment prematurely. In intention-to-treat analysis, no significant differences in change in serum fructosamine between low or high dose BTI320 and placebo were observed. Using random effect models, adjusted for variability by meals, treatment with low dose BTI320 was associated with reduction in 1-h (p < 0.01), 2-h (p = 0.01) and 3-h (p = 0.02) post-prandial incremental glucose area-under-curve and post-meal maximum glucose (p = 0.03) compared with placebo. Subjects receiving low dose BTI320 had greater body weight reduction than placebo group. CONCLUSIONS: BTI320 did not change fructosamine levels compared with placebo. BTI320 reduced glycaemic variability based on CGM indices. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov , reference number NCT02358668 (9 February 2015).
Assuntos
Galactanos/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Mananas/uso terapêutico , Gomas Vegetais/uso terapêutico , Período Pós-Prandial/efeitos dos fármacos , Estado Pré-Diabético/tratamento farmacológico , Estudo de Prova de Conceito , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , China/epidemiologia , Método Duplo-Cego , Feminino , Galactanos/efeitos adversos , Hong Kong/epidemiologia , Humanos , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Masculino , Mananas/efeitos adversos , Pessoa de Meia-Idade , Gomas Vegetais/efeitos adversos , Período Pós-Prandial/fisiologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Resultado do TratamentoRESUMO
Agaricus bisporus is one of the most important edible and medicinal mushrooms in the world. It has been well known that Agaricus bisporus has an immunoregulatory role, but its active ingredients have not been completely identified. In this study, a glucogalactomannan named TJ3 was isolated and purified from Agaricus bisporus. TJ3 (827 kDa) is composed of mannose, galactose, glucose and xylose in the ratio 28.26 : 27.82 : 20.88 : 9.87 mainly joined by ß-linkages. Functional analysis of TJ3 revealed that it effectively induced apoptosis in RAW 264.7 cells, a mouse macrophage cell line. Cell apoptosis was determined by an Annexin V/PI staining assay. After treatment with TJ3 (2 µg mL-1) for 16 h, apoptosis was observed in 34% of the Raw cells (9% in the non-treated control cells). TJ3 treatment remarkably increased the production of cleaved caspase-3, PARP and Bim, and decreased the level of Bcl-2 although no obvious change in the level of Bax was observed. Interestingly, further elucidation of the molecular mechanism underlying the role of TJ3 in the induction of apoptosis showed that TJ3 activated the JNK signaling pathway through TLR4 and subsequently promoted the expression of Bim and activation of caspase-3. Our results demonstrate that TJ3 may be a novel active component in Agaricus bisporus responsible for its immunoregulatory role by the induction of macrophage apoptosis.
Assuntos
Agaricus/química , Apoptose , Proteína 11 Semelhante a Bcl-2/agonistas , Carpóforos/química , Sistema de Sinalização das MAP Quinases , Macrófagos/metabolismo , Mananas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/metabolismo , Proteína 11 Semelhante a Bcl-2/metabolismo , Caspase 3/química , Caspase 3/metabolismo , Proliferação de Células , Sobrevivência Celular , Suplementos Nutricionais/efeitos adversos , Suplementos Nutricionais/análise , Ativação Enzimática , Etnofarmacologia , Macrófagos/citologia , Macrófagos/imunologia , Mananas/efeitos adversos , Mananas/química , Mananas/isolamento & purificação , Medicina Tradicional Chinesa , Camundongos , Estrutura Molecular , Peso Molecular , Poli(ADP-Ribose) Polimerases/metabolismo , Proteólise , Células RAW 264.7RESUMO
SCOPE: Galactomannan and citrus pectin are considered 'super fibers' known for altering gut microbiota composition and improving glucose and lipid metabolism. The study aims to investigate the fiber's effect on a nonalcoholic steatohepatitis (NASH) model. METHODS AND RESULTS: Two feeding experiments are carried out using groups of 7-8 week-old male C57BL/6J mice. The diets used are based on a high cholesterol/cholate diet (HCD), such as a nutritional NASH model. Mice are fed a diet with or without 15% fiber-citrus pectin (HCD-CP) or galactomannan (HCD-G) together with the HCD (first experiment), which commenced 3 weeks prior to the HCD (second experiment). Liver damage is evaluated by histological and biochemical parameters. Galactomannan leads to lesser weight gain and improved glucose tolerance, but increased liver damage. This is shown by elevated levels of liver enzymes compared to that with HCD alone. Fibers induce higher steatosis, as evaluated by liver histology. This intriguing result is linked to various changes in the gut microbiota, such as elevated Proteobacteria levels in the galactomannan group, which are correlated with disturbed metabolism and dysbiosis. CONCLUSIONS: In a NASH mouse model, galactomannan increases liver damage but improves glucose metabolism. Changes in the microbiota composition may answer this enigmatic observation.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Mananas/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Pectinas/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/administração & dosagem , Colesterol/efeitos adversos , Fibras na Dieta/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Galactose/análogos & derivados , Conteúdo Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Teste de Tolerância a Glucose , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
A growing population and concern over the sufficiency of natural resources for feeding this population have motivated researchers and industries to search for alternative and complementary sources of food ingredients and additives. Numerous plant species and parts of plants are explored as raw materials for food production. An interesting example is wood; to date, only a few wood-based additives or ingredients are authorized for food use. Wood hemicelluloses, such as softwood galactoglucomannans (GGM), constitute an abundant bioresource that shows a high potential functionality in edible materials. Spruce GGM acts as a multi-functional emulsion stabilizer, and it could be used in various processed food products, replacing less effective, conventional emulsifiers. Before new materials can be released into the food market, their safety must be evaluated, according to the Novel Food regulation. This review focuses on the safety aspects that must be considered before polysaccharide- and phenolic-rich plant extracts can be awarded the status of authorized food ingredients. In this review, GGM is presented as a case study and examples are given of plant-based polysaccharides that are already authorized for food purposes. The legislation regarding Novel Food ingredients in Europe is also briefly reviewed.
Assuntos
Antioxidantes/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Aditivos Alimentares/efeitos adversos , Mananas/efeitos adversos , Extratos Vegetais/efeitos adversos , Madeira/química , Animais , Suplementos Nutricionais/normas , Emulsificantes/efeitos adversos , Emulsificantes/normas , União Europeia , Aditivos Alimentares/normas , Humanos , Legislação sobre Alimentos , Fenóis/efeitos adversos , Testes de Toxicidade/normasRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG), and suppressing the gut bacteria via chronic oral administration of antibiotics. GG feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, GG enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to GG, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither GG nor antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Assuntos
Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Animais , Antibacterianos/farmacologia , Transporte Biológico , Dieta Hiperlipídica/efeitos adversos , Fibrose , Galactanos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Teste de Tolerância a Glucose , Fígado/metabolismo , Fígado/patologia , Masculino , Mananas/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/induzido quimicamente , Obesidade/metabolismo , Obesidade/microbiologia , Gomas Vegetais/efeitos adversosRESUMO
We present a case that highlights the difficulties with diagnosis and the dangers of occupational allergic sinusitis and asthma left unrecognized. We describe the case history of a man who experienced work-related symptoms 1 year after beginning work as a cheesemaker at a creamery, and whose respiratory symptoms progressively worsened over 16 years before an occupational cause of his asthma was identified. His initial discrete episodes of sinusitis and acute bronchitis evolved into persistent asthma of increasing severity with exacerbations requiring repeated emergency room treatment. The case described in our report emphasizes the importance of clinician diagnosis of OA, and subsequent removal from exposure, such that asthma severity does not progress to near-fatal or fatal asthma in the sensitized worker. As demonstrated by this case report, identification of an occupational cause of asthma relies on a high degree of suspicion and excellent detective work by the clinician.
Assuntos
Asma/induzido quimicamente , Diagnóstico Tardio , Galactanos/efeitos adversos , Mananas/efeitos adversos , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Gomas Vegetais/efeitos adversos , Sinusite/induzido quimicamente , Adulto , Asma/diagnóstico , Humanos , Masculino , Doenças Profissionais/induzido quimicamente , Testes de Função RespiratóriaRESUMO
Studies have reported a positive effect of prebiotics on the bioavailability of iron. This study evaluated the effect of partially hydrolyzed guar gum (PHGG) on iron absorption mechanisms in anemic rats. Male Wistar rats were fed 75g American Institute of Nutrition Rodent Diets for growth, pregnancy and lactation (AIN93-G) without iron for three weeks in order to induce iron deficiency anemia. Then they were fed a control diet (n = 12; without fiber) or a diet with 7.5% of PHGG (n = 12), both without iron. Food intake, body growth and the feed efficiency coefficient (FEC) were measured. The animals were euthanized after two weeks of treatment. The weight of the organs, the pH of the cecal content, and the hepatic iron and ferroportin expression in the cecum, duodenum, and liver were assessed. The intake of PHGG reduced food intake without affecting body growth, and there was a difference between the groups regarding the FEC (p = 0.026), with the highest value found in the PHGG group. The weight of the cecal content increased (p ≤ 0.001) and the pH of the cecal content was significantly lower in the PHGG group. The intake of PHGG significantly increased ferroportin expression in the cecum; however, the difference was not significant in the duodenum and the liver. PHGG seems to have a positive influence on iron absorption through transporter expression, and structural and physiological changes in the colon of anemic growing animals.
Assuntos
Anemia Ferropriva/dietoterapia , Proteínas de Transporte de Cátions/biossíntese , Ceco/metabolismo , Modelos Animais de Doenças , Galactanos/uso terapêutico , Mucosa Intestinal/metabolismo , Mananas/uso terapêutico , Gomas Vegetais/uso terapêutico , Prebióticos , Anemia Ferropriva/sangue , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Animais , Biomarcadores/sangue , Proteínas de Transporte de Cátions/metabolismo , Ceco/patologia , Colo/metabolismo , Colo/patologia , Ingestão de Energia , Galactanos/efeitos adversos , Galactanos/metabolismo , Hidrólise , Absorção Intestinal , Mucosa Intestinal/patologia , Ferro/metabolismo , Ferro da Dieta/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Mananas/efeitos adversos , Mananas/metabolismo , Tamanho do Órgão , Especificidade de Órgãos , Gomas Vegetais/efeitos adversos , Gomas Vegetais/metabolismo , Prebióticos/efeitos adversos , Ratos Wistar , Aumento de PesoRESUMO
Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 µm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy.
Assuntos
Antituberculosos/administração & dosagem , Galactanos/administração & dosagem , Macrófagos Alveolares/efeitos dos fármacos , Mananas/administração & dosagem , Gomas Vegetais/administração & dosagem , Tuberculose/tratamento farmacológico , Células A549 , Administração por Inalação , Antituberculosos/efeitos adversos , Antituberculosos/química , Sistemas de Liberação de Medicamentos , Galactanos/efeitos adversos , Galactanos/química , Humanos , Macrófagos Alveolares/patologia , Mananas/efeitos adversos , Mananas/química , Microesferas , Mycobacterium tuberculosis/efeitos dos fármacos , Tamanho da Partícula , Fagocitose/efeitos dos fármacos , Gomas Vegetais/efeitos adversos , Gomas Vegetais/químicaRESUMO
BACKGROUND: No prior studies have examined injection pain associated with Technetium-99m Tilmanocept (TcTM). METHODS: This was a randomized, double-blinded study comparing postinjection site pain between filtered Technetium Sulfur Colloid (fTcSC) and TcTM in breast cancer lymphoscintigraphy. Pain was evaluated with a visual analogue scale (VAS) (0-100 mm) and the short-form McGill Pain Questionnaire (SF-MPQ). The primary endpoint was mean difference in VAS scores at 1-min postinjection between fTcSC and TcTM. Secondary endpoints included a comparison of SF-MPQ scores between the groups at 5 min postinjection and construction of a linear mixed effects model to evaluate the changes in pain during the 5-min postinjection period. RESULTS: Fifty-two patients underwent injection (27-fTcSC, 25-TcTM). At 1-min postinjection, patients who received fTcSC experienced a mean change in pain of 16.8 mm (standard deviation (SD) 19.5) compared with 0.2 mm (SD 7.3) in TcTM (p = 0.0002). At 5 min postinjection, the mean total score on the SF-MPQ was 2.8 (SD 3.0) for fTcSC versus 2.1 (SD 2.5) for TcTM (p = 0.36). In the mixed effects model, injection agent (p < 0.001), time (p < 0.001) and their interaction (p < 0.001) were associated with change in pain during the 5-min postinjection period. The model found fTcSC resulted in significantly more pain of 15.2 mm (p < 0.001), 11.3 mm (p = 0.001), and 7.5 mm (p = 0.013) at 1, 2, and 3 min postinjection, respectively. CONCLUSIONS: Injection with fTcSC causes significantly more pain during the first 3 min postinjection compared with TcTM in women undergoing lymphoscintigraphy for breast cancer.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Dextranos/efeitos adversos , Linfocintigrafia/efeitos adversos , Mananas/efeitos adversos , Dor/diagnóstico , Biópsia de Linfonodo Sentinela/efeitos adversos , Pentetato de Tecnécio Tc 99m/análogos & derivados , Coloide de Enxofre Marcado com Tecnécio Tc 99m/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dor/etiologia , Prognóstico , Compostos Radiofarmacêuticos/efeitos adversos , Pentetato de Tecnécio Tc 99m/efeitos adversosRESUMO
We describe a novel wound dressing (HR006) with two components: a lyophilized matrix of the galactomannan from locust bean gum (LBG) and an antioxidant hydration solution (AHsol) containing curcumin and N-acetyl-L-cysteine (NAC). Physico-structural analyses of the LBG matrix revealed homogeneous interconnected pores with high absorbing capacity showing excellent properties for moist wound care (MWC). In an in vitro oxidative stress fibroblast injury model, the AHsol showed relevant protective effects reducing intracellular reactive oxygen species (ROS) production, rescuing cell viability, and regulating expression of inflammation-related genes (COX-2, TNF-α, IL-1α, IL-1ß). The new dressing showed good biocompatibility profile as demonstrated by cytotoxicity, hemocompatibility, and skin irritation tests. Moreover, in an in vivo skin wound model in pigs, this dressing enhanced the production of healthy and organized granulation tissue and re-epithelization. In summary, HR006 exhibits significant antioxidant activity, good biocompatibility, and excellent repair capabilities improving tissue remodeling and the healing of wounds.
Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Bandagens , Mananas/administração & dosagem , Mananas/uso terapêutico , Cicatrização/efeitos dos fármacos , Acetilcisteína/farmacologia , Animais , Bandagens/efeitos adversos , Curcumina/farmacologia , Citocinas/biossíntese , Citocinas/genética , Fibroblastos/efeitos dos fármacos , Galactanos , Galactose/análogos & derivados , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Irritantes , Mananas/efeitos adversos , Teste de Materiais , Estresse Oxidativo/efeitos dos fármacos , Gomas Vegetais , Espécies Reativas de Oxigênio/metabolismo , Sus scrofaRESUMO
In this issue of Blood, Uryu et al demonstrate that recognition of a fungal cell wall component, α-mannan (Mn), an Mn (sugar) polymer, by the C-type lectin receptor Dectin-2 on host macrophages leads to a lung chemokine environment conducive to donor T helper (Th)17 accumulation resulting in severe pulmonary graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). These findings shed new light on a long-standing gap in our understanding of the mechanistic link between infections, specifically fungal, and GVHD severity following allo-HSCT.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Interleucina-17/fisiologia , Pneumopatias/etiologia , Mananas/efeitos adversos , Células Th17/imunologia , Animais , FemininoRESUMO
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Interleucina-17/fisiologia , Pneumopatias/etiologia , Mananas/efeitos adversos , Células Th17/imunologia , Animais , Western Blotting , Candida albicans/fisiologia , Candidíase/imunologia , Candidíase/microbiologia , Candidíase/patologia , Células Cultivadas , Feminino , Citometria de Fluxo , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Interferon gama/metabolismo , Pneumopatias/mortalidade , Pneumopatias/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Transplante HomólogoRESUMO
In spite of the various bioavailable formulations of curcumin for pharma and dietary supplement applications, food grade formulations suitable as a dietary ingredient, and capable of providing significant levels of plasma curcumin, are limited. The present contribution describes the safety and oral bioavailability of a novel water soluble formulation of curcumin, curcumagalactomannosides (CGM), when used as a dietary ingredient in selected food items. CGM was prepared using a food grade hydrocolloid (galactomannans) derived from the kitchen spice fenugreek (Trigonella foenum graccum), without using any synthetic excipients. The safety of the formulation was assessed through acute and subchronic toxicity studies on Wistar rats and genotoxicity studies. The efficacy of CGM as a bioavailable dietary ingredient was assessed by successfully preparing various food items and by measuring the post-blood plasma curcumin levels at various time intervals after the consumption of food items. High performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA) and electrospray ionization tandem mass spectrometer (ESI-MS/MS) was employed for the quantification of plasma curcuminoids. It was observed that CGM is safe and suitable for further development and clinical studies, with a no observable adverse effect level (NOAEL) up to 2.0 g kg⻹ per day b.wt. CGM was found to offer seven to ten times higher bioavailability of curcumin in humans, when incorporated into various food/beverage items at 100 mg CGM per serving size, as compared to the standard unformulated curcumin.
Assuntos
Anticarcinógenos/administração & dosagem , Curcumina/análogos & derivados , Alimentos Especializados/análise , Absorção Intestinal , Mananas/química , Manosídeos/química , Adulto , Animais , Anticarcinógenos/efeitos adversos , Anticarcinógenos/química , Anticarcinógenos/metabolismo , Coloides , Curcumina/efeitos adversos , Curcumina/química , Curcumina/metabolismo , Feminino , Alimentos Especializados/efeitos adversos , Galactose/análogos & derivados , Humanos , Índia , Masculino , Mananas/administração & dosagem , Mananas/efeitos adversos , Mananas/metabolismo , Manosídeos/administração & dosagem , Manosídeos/efeitos adversos , Manosídeos/metabolismo , Testes de Mutagenicidade , Nível de Efeito Adverso não Observado , Ratos Sprague-Dawley , Ratos Wistar , Solubilidade , Especiarias/análise , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Trigonella/químicaRESUMO
Strategically developed natural polymer-based controlled release multiparticulate drug delivery systems have gained special interest for "spatial placement" and "temporal delivery" of drug molecules. In our earlier study, locust bean gum-poly(vinyl alcohol) interpenetrating polymer network (LBG-PVA IPN), carboxymethylated locust bean gum-poly(vinyl alcohol) interpenetrating polymer network (CMLBG-PVA IPN) and acrylamide grafted locust bean gum-poly(vinyl alcohol) interpenetrating polymer network (Am-g-LBG-PVA IPN) were prepared and characterized. The present study deals with accelerating stability testing, comparative bio-safety and single dose in vivo pharmacokinetic study of all three IPN microspheres for controlled oral delivery of buflomedil hydrochloride (BH). From the stability study, it was observed that the particles were stable throughout the study period. From toxicity and biodegradability study it was proved that the microspheres were safe for internal use and complied with bio-safety criterion. From the in vivo pharmacokinetic study in rabbits, it was observed that the CMLBG-PVA IPN microspheres possessed almost similar Tmax value with BH oral suspension. However, in comparison between the LBG-PVA and Am-g-LBG-PVA IPN microspheres, the later showed well controlled release property than the first in biological condition. Thus, this type of delivery system might be useful to achieve the lofty goals of the controlled release drug delivery.