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1.
J Immunol Res ; 2024: 6876247, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939744

RESUMEN

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.


Asunto(s)
Modelos Animales de Enfermedad , Sepsis , Animales , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Sepsis/terapia , Humanos , Ratones , Glucanos/uso terapéutico , Glucanos/farmacología , beta-Glucanos/uso terapéutico , Inmunomodulación/efectos de los fármacos
2.
Rev. bras. cir. plást ; 39(2): 1-6, abr.jun.2024. ilus
Artículo en Inglés, Portugués | LILACS-Express | LILACS | ID: biblio-1556475

RESUMEN

Introdução: A fissura labiopalatina é a deformidade congênita mais comum, com uma incidência de 1,53/1000 nascidos vivos e o tratamento predominantemente realizado no Sistema Único de Saúde (SUS). Em 1999, o Sistema de Informações sobre Nascidos Vivos (SINASC) implantou a lacuna para preenchimento referente a deformidade congênita. Trabalhos vêm demostrando a subnotificação importante da fissura no SINASC. Método: Foi levantado o número de crianças nascidas por ano no Brasil entre 2012 e 2018 nas respectivas regiões, projetando o número de fissurados nascidos por ano usando a proporção 1,53/1000 nascidos vivos. A partir destes dados, observado o número de fissurados notificados no sistema SUS e comparado com a projeção feita observando uma estimativa de notificação por região. Verificada também a evolução dos gastos governamentais por região com cirurgia de fissura labiopalatina no período de 2012 a 2018. Resultados: Houve uma notificação de 54,1% a 36,7% das crianças nascidas com fissura, sendo a Região Sudeste com melhor índice e o Nordeste com o índice mais baixo de notificação. Os gastos federais em cirurgia de fissura labiopalatina diminuíram entre 2012 e 2018, frente ao número de nascimentos com fissuras, que se manteve estável neste período. Conclusão: Apesar do SINASC ser uma ferramenta importante, as subnotificações expressivas desta afecção impactam nas políticas públicas, pois utilizam dados inconsistentes com a realidade. Outra preocupação é a diminuição dos gastos federais com cirurgias de fissurados, o que demostra que mais crianças estão deixando de receber tratamento adequado.


Introduction: Cleft lip and palate is the most common congenital deformity, with an incidence of 1.53/1000 live births, and treatment is predominantly carried out in the Unified Health System (Sistema Único de Saúde SUS). In 1999, the Live Birth Information System (Sistema de Informações sobre Nascidos Vivos SINASC) implemented the gap to be filled in regarding congenital deformities. Studies have demonstrated the significant underreporting of the fissure in SINASC. Method: The number of children born per year in Brazil between 2012 and 2018 was surveyed in the respective regions, projecting the number of cleft children born per year using the proportion 1.53/1000 live births. From these data, the number of cleft patients notified in the SUS system was observed and compared with the projection made by observing an estimate of notification by region. The evolution of government spending by region on cleft lip and palate surgery in the period from 2012 to 2018 was also verified. Results: There was a notification of 54.1% to 36.7% of children born with cleft, with the Southeast Region having the best rate and the Northeast with the lowest notification rate. Federal spending on cleft lip and palate surgery decreased between 2012 and 2018, compared to the number of births with clefts, which remained stable during this period. Conclusion: Although SINASC is an important tool, the significant underreporting of this condition impacts public policies, as it uses data inconsistent with reality. Another concern is the decrease in federal spending on cleft surgery, which shows that more children are failing to receive adequate treatment.

3.
Gynecol Oncol ; 186: 53-60, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599112

RESUMEN

OBJECTIVES: To identify predictors of referral and completion of germline genetic testing among newly diagnosed ovarian cancer patients, with a focus on geographic social deprivation, oncologist-level practices, and time between diagnosis and completion of testing. METHODS: Clinical and sociodemographic data were abstracted from medical records of patients newly diagnosed with ovarian cancer between 2014 and 2019 in the University of North Carolina Health System. Factors associated with referral for genetic counseling, completion of germline testing, and time between diagnosis and test results were identified using multivariable regression. RESULTS: 307/459 (67%) patients were referred for genetic counseling and 285/459 (62%) completed testing. The predicted probability of test completion was 0.83 (95% CI: 0.77-0.88) for patients with a referral compared to 0.27 (95% CI: 0.18-0.35) for patients without a referral. The predicted probability of referral was 0.75 (95% CI: 0.69-0.82) for patients at the 25th percentile of ZIP code-level Social Deprivation Index (SDI) and 0.67 (0.60-0.74) for patients at the 75th percentile of SDI. Referral varied by oncologist, with predicted probabilities ranging from 0.47 (95% CI: 0.32-0.62) to 0.93 (95% CI: 0.85-1.00) across oncologists. The median time between diagnosis and test results was 137 days (IQR: 55-248 days). This interval decreased by a predicted 24.46 days per year (95% CI: 37.75-11.16). CONCLUSIONS: We report relatively high germline testing and a promising trend in time from diagnosis to results, with variation by oncologist and patient factors. Automated referral, remote genetic counseling and sample collection, reduced out-of-pocket costs, and educational interventions should be explored.


Asunto(s)
Asesoramiento Genético , Pruebas Genéticas , Mutación de Línea Germinal , Neoplasias Ováricas , Derivación y Consulta , Humanos , Femenino , Derivación y Consulta/estadística & datos numéricos , Neoplasias Ováricas/genética , Neoplasias Ováricas/diagnóstico , Persona de Mediana Edad , Pruebas Genéticas/estadística & datos numéricos , Pruebas Genéticas/métodos , Asesoramiento Genético/estadística & datos numéricos , Adulto , Anciano , North Carolina , Instituciones Oncológicas/estadística & datos numéricos , Estudios Retrospectivos
4.
Biomolecules ; 14(4)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38672459

RESUMEN

TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters were assessed in wild-type (WT) and global TRPC5 knockout (KO) mice. Despite no difference in blood pressure or activity, heart rate was significantly reduced in TRPC5 KO mice. Echocardiography imaging revealed an increase in stroke volume, but cardiac contractility was unaffected. The reduced heart rate persisted in isolated TRPC5 KO hearts, suggesting changes in basal cardiac pacing. Heart rate was further investigated by evaluating the reflex change following drug-induced pressure changes. The reflex bradycardic response following phenylephrine was greater in TRPC5 KO mice but the tachycardic response to SNP was unchanged, indicating an enhancement in the parasympathetic control of the heart rate. Moreover, the reduction in heart rate to carbachol was greater in isolated TRPC5 KO hearts. To evaluate the role of TRPC5 in cardiac pathology, mice were subjected to abdominal aortic banding (AAB). An exaggerated cardiac hypertrophy response to AAB was observed in TRPC5 KO mice, with an increased expression of hypertrophy markers, fibrosis, reactive oxygen species, and angiogenesis. This study provides novel evidence for a direct effect of TRPC5 on cardiac function. We propose that (1) TRPC5 is required for maintaining heart rate by regulating basal cardiac pacing and in response to pressure lowering, and (2) TRPC5 protects against pathological cardiac hypertrophy.


Asunto(s)
Cardiomegalia , Frecuencia Cardíaca , Ratones Noqueados , Canales Catiónicos TRPC , Animales , Canales Catiónicos TRPC/metabolismo , Canales Catiónicos TRPC/genética , Cardiomegalia/metabolismo , Ratones , Masculino , Miocitos Cardíacos/metabolismo , Ratones Endogámicos C57BL , Presión Sanguínea
6.
Food Res Int ; 173(Pt 1): 113334, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803644

RESUMEN

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the gastrointestinal tract. The etiology is not fully understood, but environmental, microbial, and immunologic factors, as well as a genetic predisposition, play a role. UC is characterized by episodes of abdominal pain, diarrhea, bloody stools, weight loss, severe colonic inflammation, and ulceration. Despite the increase in the frequency of UC and the deterioration of the quality of life, there are still patients who do not respond well to available treatment options. Against this background, natural products such as polysaccharides are becoming increasingly important as they protect the intestinal mucosa, promote wound healing, relieve inflammation and pain, and restore intestinal motility. In this study, we investigated the effect of a polysaccharide isolated from the biomass of Campomanesia adamantium and Campomanesia pubescens (here referred to as CPW) in an experimental model of acute and chronic ulcerative colitis induced by dextran sulfate sodium (DSS). CPW reversed weight loss, increased disease activity index (DAI), bloody diarrhea, and colon shortening. In addition, CPW reduced visceral mechanical hypersensitivity, controlled oxidative stress and inflammation, and protected the mucosal barrier. CPW is not absorbed in the intestine, does not inhibit cytochrome P450 proteins, and does not exhibit AMES toxicity. These results suggest that CPW attenuates DSS-induced acute and chronic colitis in mice and may be a potential alternative treatment for UC.


Asunto(s)
Colitis Ulcerosa , Humanos , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Calidad de Vida , Modelos Animales de Enfermedad , Inflamación , Pérdida de Peso , Diarrea
7.
JAMA Netw Open ; 6(10): e2335941, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37782500

RESUMEN

Importance: Patients with early breast cancer must choose between undergoing breast conservation surgery or mastectomy. This decision is often difficult as there are trade-offs between breast conservation and adverse effects, and women with higher decisional conflict have a harder time choosing the therapy that suits their preferences. Objective: To study the impact of a decision aid with a patient preference assessment tool for surgical decision-making on patients' decisional conflict scale (DCS) score. Design, Setting, and Participants: This 3-group randomized clinical trial was conducted between June 2017 and December 2019 at a single high-volume tertiary care cancer center in Mumbai, India. A research questionnaire comprising 16 questions answered on a Likert scale (from 1, strongly agree, to 5, strongly disagree) was used to measure DCS scores and other secondary psychological variables, with higher scores indicating more decisional conflict. The Navya Patient Preference Tool (Navya-PPT) was developed as a survey-based presentation of evidence in an adaptive, conjoint analysis-based module for and trade-offs between cosmesis, adverse effects of radiotherapy, and cost of mandatory radiation following breast-conserving surgery. Adult patients with histologically proven early breast cancer (cT1-2, N0-1) who were eligible for breast-conserving surgery as per clinicoradiological assessment were included. Those who were pregnant or unable to read the research questionnaire or who had bilateral breast cancer were excluded. Data were analyzed from January to June 2020. Interventions: Patients were randomized 1:1:1 to study groups: standard care including clinical explanation about surgery (control), standard care plus the Navya-PPT provided to the patient alone (solo group), and standard care plus the Navya-PPT provided to the patient and a caregiver (joint group). Main Outcomes and Measures: The primary end point of the study was DCS score. The study was 80% powered with 2-sided α = .01 to detect an effect size of 0.25 measured by Cohen d, F test analysis of variance, and fixed effects. Results: A total of 245 female patients (median [range] age, 48 [23-76] years) were randomized (82 to control, 83 to the solo group, and 80 to the joint group). The median (range) pathological tumor size was 2.5 (0-6) cm. A total of 153 participants (62.4%) had pN0 disease, 185 (75.5%) were hormone receptor positive, 197 (80.4%) were human epidermal growth factor receptor 2 negative, 144 (58.6%) were of middle or lower socioeconomic status, and 114 (46.5%) had an education level lower than a college degree. DCS score was significantly reduced in the solo group compared with control (1.34 vs 1.66, respectively; Cohen d, 0.50; SD, 0.31; P < .001) and the joint group compared with control (1.31 vs 1.66, respectively; Cohen d, 0.54; SD, 0.31; P < .001). Conclusions and Relevance: The results of this study demonstrated lower decisional conflict as measured by DCS score following use of the online, self-administered Navya-PPT among patients with early breast cancer choosing between breast-conserving surgery vs mastectomy. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/11/010480.


Asunto(s)
Neoplasias de la Mama , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adulto , Embarazo , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Mastectomía , Mama , Técnicas de Apoyo para la Decisión
8.
J Immunol Res ; 2023: 2868707, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37621924

RESUMEN

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5 mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12 hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.


Asunto(s)
Granada (Fruta) , Sepsis , Femenino , Animales , Ratones , Longevidad , Sepsis/tratamiento farmacológico , Anticuerpos , Citocinas
9.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37631015

RESUMEN

Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.

10.
BMC Oral Health ; 23(1): 602, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37641077

RESUMEN

BACKGROUND: Many orthodontic patients request dental bleaching during orthodontic treatment to achieve a faster aesthetic resolution, however, no attention has been paid to the inflammatory processes that can occur when both therapies are indicated together. So, this clinical trial evaluated the inflammatory parameters and color alterations associated with dental bleaching in patients wearing a fixed orthodontic appliance. METHODS: Thirty individuals aged between 18 and 40 years were equally and randomly allocated into three groups: FOA (fixed orthodontic appliance), BLE (dental bleaching), and FOA + BLE (fixed orthodontic appliance + dental bleaching). The orthodontic appliances and the bleaching procedures were performed in the maxillary premolars and molars. For dental bleaching a 35% hydrogen peroxide was used. The gingival crevicular fluid (GCF) and nitric oxide (NO-) levels were evaluated at different time-points. Color evaluation was performed using an Easyshade spectrophotometer at baseline (FOA, FOA + BLE, BLE), one month after (FOA + BLE) and 21 days after appliance removing (FOA + BLE and FOA groups), in each tooth bleached. The ANOVA and Tukey's tests, with a significance level of 5%, were used for statistical analysis. RESULTS: The GCF volume in the FOA + BLE and FOA groups significantly increased at the time points evaluated (p < 0.001); however, this did not occur in the BLE group (p > 0.05). On the other hand, NO- levels significantly decreased during dental bleaching with or without fixed orthodontic appliances (FOA + BLE and BLE groups; p < 0.05), while no significant changes were observed in the FOA group (p > 0.05). Significant changes in color were observed in the FOA + BLE and BLE groups compared to in the FOA group (p < 0.01). However, the presence of fixed orthodontic appliance (FOA + BLE) negatively affected the bleaching efficacy compared to BLE group (p < 0.01). CONCLUSIONS: Dental bleaching did not increase the inflammatory parameters in patients wearing fixed orthodontic appliance. However, in the presence of orthodontic appliances, the bleaching efficacy was lower than that of bleaching teeth without orthodontic appliances. TRIAL REGISTRATION: RBR-3sqsh8 (first trial registration: 09/07/2018).


Asunto(s)
Aparatos Ortodóncicos Fijos , Aparatos Ortodóncicos , Humanos , Adolescente , Adulto Joven , Adulto , Aparatos Ortodóncicos Fijos/efectos adversos , Aparatos Ortodóncicos/efectos adversos , Pacientes , Peróxido de Hidrógeno , Atención Odontológica , Óxido Nítrico
11.
Antibiotics (Basel) ; 12(6)2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37370369

RESUMEN

Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, including plants, microorganisms, and animals, have since become a growing area of research. In this context, studies covering the investigation of their ability to combat resistant microorganisms, either by neutralization or inactivation of pathogen resistance mechanisms and virulence properties, have gained attention. Herein, a collection of 19 manuscripts focused on the antimicrobial and anti-infective activity of natural products, including their mechanisms of action, in silico evidence of antimicrobial activity, synergistic associations with antibiotics, and other aspects, will be discussed.

12.
Viruses ; 15(6)2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37376604

RESUMEN

INTRODUCTION: Although fewer children have been affected by the severe form of the coronavirus disease 2019 (COVID-19), community-acquired pneumonia (CAP) continues to be the leading global cause of child hospitalizations and deaths. AIM: This study investigated the incidence of respiratory syncytial virus (RSV) as well its subtypes (RSV A and B), adenovirus (ADV), rhinovirus (HRV), metapneumovirus (HMPV), coronavirus (NL63, OC43, 229E and HKU1), parainfluenza virus subtypes (PI1, PI2 and PI3), bocavirus and influenza A and B viruses (FluA and FluB) in children diagnosed with CAP during the COVID-19 pandemic. METHODS: A total of 200 children with clinically confirmed CAP were initially recruited, of whom 107 had negative qPCR results for SARS-CoV-2 and were included in this study. Viral subtypes were identified using a real-time polymerase chain reaction in the nasopharyngeal swab samples. RESULTS: Viruses were identified in 69.2% of the patients. RSV infections were the most frequently identified (65.4%), with type RSV B being the most prevalent (63.5%). In addition, HCoV 229E and HRV were detected in 6.5% and 3.7% of the patients, respectively. RSV type B was associated with severe acute respiratory infection (ARI) and a younger age (less than 24 months). CONCLUSIONS: New strategies for preventing and treating viral respiratory infections, particularly RSV infections, are necessary.


Asunto(s)
COVID-19 , Infecciones Comunitarias Adquiridas , Neumonía , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Humanos , Niño , Lactante , Preescolar , Incidencia , Brasil/epidemiología , Pandemias , COVID-19/epidemiología , SARS-CoV-2 , Virus Sincitial Respiratorio Humano/genética , Neumonía/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones Comunitarias Adquiridas/epidemiología
13.
Food Chem Toxicol ; 177: 113852, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37244598

RESUMEN

The ostrich oil (OO) has been topically used for decades to treat skin diseases. Its oral use has been encouraged through e-commerce advertising several health benefits to OO without scientific evidence on its safety or effectiveness. This study presents the chromatographic profile of a commercially available OO and its acute and 28-day repeated dose in vivo toxicological profiles. OO anti-inflammatory and antinociceptive effects were also investigated. Omega-9 (ω-9; oleic acid; 34.6%) and -6 (linoleic acid; 14.9%) were detected as OO main constituents. A high single dose of the OO (2 g/kg of ω-9) demonstrated no or low acute toxicity. However, when orally treated with OO (30-300 mg/kg of ω-9) for 28 consecutive days, mice exhibited altered locomotor and exploratory activities, hepatic damage, and increased hindpaw sensitivity accompanied by increased levels of cytokine and brain-derived neurotrophic factor in their spinal cords and brains. Lack of anti-inflammatory or antinociceptive activities was also evidenced in 15-day-OO treated mice. These results indicate that chronic consumption of OO induces hepatic injury, in addition to neuroinflammation and subsequent hypersensitivity and behavioural changes. Thus, there is no evidence to support OO use to treating illness in humans.


Asunto(s)
Struthioniformes , Humanos , Animales , Ratones , Aceite de Oliva/química , Enfermedades Neuroinflamatorias , Pruebas de Toxicidad , Analgésicos/toxicidad
14.
Drug Discov Today ; 28(7): 103626, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37224998

RESUMEN

Antineoplastic treatment induces a type of gastrointestinal toxicity known as mucositis. Findings in animal models are usually easily reproducible, and standardized treatment regimens are often used, thus supporting translational science. Essential characteristics of mucositis, including intestinal permeability, inflammation, immune and oxidative responses, and tissue repair mechanisms, can be easily investigated in these models. Given the effects of mucositis on the quality of life of patients with cancer, and the importance of experimental models in the development of more effective new therapeutic alternatives, this review discusses progress and current challenges in using experimental models of mucositis in translational pharmacology research.


Asunto(s)
Antineoplásicos , Mucositis , Animales , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Roedores , Calidad de Vida , Antineoplásicos/toxicidad , Desarrollo de Medicamentos , Mucosa Intestinal
15.
Nutr Cancer ; 75(5): 1382-1398, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36974004

RESUMEN

Gastrointestinal toxicity, including diarrhea and inflammation, is commonly observed with the use of 5-fluorouracil (5-FU). Several studies have shown that polysaccharides are interesting bioactive macromolecules for the treatment or prevention of gastrointestinal diseases. Therefore, in this study, the effect of a polysaccharide fraction from a mixture of two Guavira species (Campomanesia adamantium and Campomanesia pubescens), referred to here as CPW, on the development of intestinal mucositis was investigated. Intestinal mucositis was induced by a single injection of 5-FU (450 mg/kg), and various doses of CPW (3-100 mg/kg) were tested. CPW attenuated disease development and prevented small bowel dysmotility and colon shortening. CPW prevented the increase in villi width, crypt depth, and mucosal thickness in the duodenum, but not in the colon. Preservation of mucus, reduction of oxidative stress, inflammation, and prevention of the 5-FU-induced enlargement and swelling of the spleen were observed. In conclusion, this study demonstrated for the first time that CPW alleviates the intestinal damage induced by 5-FU and could be used as an adjuvant strategy during chemotherapy.


Asunto(s)
Fluorouracilo , Mucositis , Ratones , Animales , Fluorouracilo/toxicidad , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/prevención & control , Antimetabolitos Antineoplásicos/toxicidad , Mucosa Intestinal , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Polisacáridos/farmacología
16.
Int Immunopharmacol ; 115: 109669, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36634418

RESUMEN

Cinnamaldehyde is a natural product with anti-inflammatory and immune-modulatory properties, known to regulate host responses to bacterial stimuli. This study aimed to investigate the effects of cinnamaldehyde on ligature-induced periodontitis in rats, and its impact on the modulation of human peripheral blood mononuclear cells (PBMC). Male Wistar rats were assigned into three groups:i) control: no ligature + vehicle; ii) ligature: ligature + vehicle; and iii) ligature + cinnamaldehyde (50 mg/kg); all treatments by daily oral gavage. After 14 days of induced periodontitis, the hemimandibles were collected for bone loss evaluation. The gingival levels of IL-1ß, MMP-9 and iNOS mRNA were evaluated. Nitric oxide (NO) was measured in both rat saliva and plasma. PBMC were stimulated with Aggregatibacter actinomycetemcomitans (Aa) in the presence or absence of cinnamaldehyde (5, 20 e 40 µM), and cytokine production was quantified in cell supernatant. Proliferating lymphocytes were taken for flow cytometer reading, while culture supernatants were used for IFN-γ and IL-10 assessment. The ligature group had both increased alveolar bone loss and gingival expression of IL-1ß, MMP-9 and iNOS compared to the control group. All parameters were attenuated by cinnamaldehyde treatment. Lower salivary but not plasma NO was detected in the cinnamaldehyde compared to the ligature group. Aa-stimulated PBMCs treated with cinnamaldehyde produced less IL-1ß; the compound also attenuated lymphocyte proliferation in a dose-dependent manner, as well as cell IL-10 production. Cinnamaldehyde treatment reduced periodontal bone loss, and downregulated key inflammatory mediators and human PBMC responses, pointing to novel potential therapeutic effects of this compound.


Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Leucocitos Mononucleares/metabolismo , Interleucina-10/uso terapéutico , Metaloproteinasa 9 de la Matriz , Periodontitis/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Modelos Animales de Enfermedad
17.
Antibiotics (Basel) ; 11(12)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36551490

RESUMEN

In folk medicine, Vismia guianensis is used to treat skin diseases and mycoses in the Amazon region. We evaluated the anti-Candida activity of the hydroalcoholic extract from the leaves of Vismia guianensis (EHVG). HPLC-PDA and FIA-ESI-IT-MSn were used to chemically characterize EHVG. The anti-Candida activity was determined in vitro by the minimum inhibitory concentrations (MIC) against Candida glabrata (ATCC-2001); Candida albicans (ATCC-90028, ATCC-14053, and ATCC-SC5314), and C. albicans clinical isolates. EHVG effects on adhesion, growth, and biofilm formation were also determined. Molecular docking was used to predict targets for EHVG compounds. The main compounds identified included anthraquinone, vismione D, kaempferol, quercetin, and vitexin. EHVG was fungicidal against all tested strains. C. albicans ATCC 14053 and C. glabrata ATCC 2001 were the most sensitive strains, as the extract inhibited their virulence factors. In silico analysis indicated that vismione D presented the best antifungal activity, since it was the most effective in inhibiting CaCYP51, and may act as anti-inflammatory and antioxidant agent, according to the online PASS prediction. Overall, the data demonstrate that EHVG has an anti-Candida effect by inhibiting virulence factors of the fungi. This activity may be related to its vismione D content, indicating this compound may represent a new perspective for treating diseases caused by Candida sp.

18.
Antibiotics (Basel) ; 11(12)2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36551499

RESUMEN

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings.

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