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1.
Pharmacol Res ; 196: 106947, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37797660

RESUMO

Hydrogen sulfide (H2S) has been extensively studied as a signal molecule in the body for the past 30 years. Researchers have conducted studies using both natural and synthetic sources of H2S, known as H2S donors, which have different characteristics in terms of how they release H2S. These donors can be inorganic salts or have various organic structures. In recent years, certain types of sulfur compounds found naturally in foods have been characterized as H2S donors and explored for their potential health benefits. These compounds are referred to as "sulfanutraceuticals," a term that combines "nutrition" and "pharmaceutical". It is used to describe products derived from food sources that offer additional health advantages. By introducing the terms "sulfaceuticals" and "sulfanutraceuticals," we categorize sulfur-containing substances based on their origin and their use in both preclinical and clinical research, as well as in dietary supplements.


Assuntos
Sulfeto de Hidrogênio , Compostos de Enxofre/uso terapêutico , Enxofre
2.
Eur J Orthod ; 45(6): 781-787, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-37503575

RESUMO

BACKGROUND/OBJECTIVES: The aim of this trial was to investigate the effect of mastic mouthwash on halitosis using as a proxy the levels of the Volatile Sulfur Compounds (VSCs), and the effect on plaque and gingival indices in adolescents undergoing orthodontic treatment with fixed conventional labial appliances. SUBJECTS/METHODS: The study was a double-blinded, placebo-controlled, parallel-group, randomized clinical trial. Thirty patients with fixed orthodontic appliances were randomly allocated at a 1:1 ratio, to either the mastic-mouthwash or the placebo-mouthwash group. Eligibility criteria included ages between 13 and 18, active orthodontic treatment with fixed appliances, good general health, and total initial VSCs levels above 150 ppb. The primary outcome was the objective hydrogen sulfide (H2S) level, measured with the Oral ChromaTM device. The secondary outcomes were (1.) the methyl-mercaptan (CH3SH) and (2.) dimethyl sulfide [(CH3)2S] levels, measured with the same device, (3.) the subjective perception of the own malodour via questionnaires, and (4.) the oral hygiene assessed with the use of the Modified Silness and Löe Plaque Index (PI-M) and the Silness and Löe Gingival Index (GI) at baseline (T0) and after 2 weeks (T1). Stratified randomization by gender was used, and allocation was concealed with opaque numbered sealed envelopes. RESULTS: H2S level dropped from 221.00 ppb (T0) to 125.00 ppb (T1), and the difference between treatment groups was statistically significant in favour of the mastic group (coef: 72.34, 95% CI: 8.48, 136.27, P = 0.03). The levels of the other VSCs, the subjective measurements of oral malodour, and the oral hygiene indices did not differ between treatment arms. LIMITATIONS: The objective organoleptic assessment by a calibrated examiner was not performed. CONCLUSIONS/IMPLICATIONS: Mastic mouthwashes could be an alternative treatment for adolescent patients suffering from halitosis during orthodontic treatment with fixed appliances. REGISTRATION: The trial was registered at ClinicalTrials.gov (identifier: NCT05647369).


Assuntos
Placa Dentária , Halitose , Adolescente , Humanos , Halitose/prevenção & controle , Halitose/tratamento farmacológico , Higiene Bucal , Antissépticos Bucais/uso terapêutico , Compostos de Enxofre/uso terapêutico , Placa Dentária/prevenção & controle , Placa Dentária/tratamento farmacológico
3.
Artigo em Inglês | MEDLINE | ID: mdl-36278448

RESUMO

Aged garlic extract (AGE) is an odorless derivative of garlic prepared by extracting garlic cloves in an aqueous solution for twenty months. During the process of aging, reactive organosulfur compounds such as allicin present in garlic are converted to their stable isoforms such as S- Allyl cysteine. The unstable organo sulfurs in garlic (Allium sativum L.) have been reported to cause problems in the gastrointestinal (GI) tract with an extremely pungent odor to attain its therapeutic potential. But these pharmacologically safer sulfur compounds of AGE have been studied and reported to have exceptional therapeutic potential in human health and various diseases. SAllyl cysteine (SAC), Diallyl disulfide (DADS), Diallyl trisulfide (DATS), S-allyl-mercaptocysteine (SAMC), are the most studied organosulfur compounds in in-vitro as well as in-vivo research. Biomedical research suggests that these phytoconstituents exhibit antioxidant, cardioprotective, cancer preventive, neuroprotective, immunomodulatory, antilipidemic, antidiabetic, hepatoprotective, and antiobesity effects. The therapeutic potential of aged garlic extract has been found to be extensively beneficial in these conditions, and provide a vast future in biomedical chemistry, herbdrug synergy and drug designing. The purpose of this review is to provide a mechanistic understanding of various organosulfur compounds of AGE in human health and disease based on data provided in the literature.


Assuntos
Alho , Humanos , Lactente , Idoso , Alho/química , Antioxidantes/uso terapêutico , Compostos de Enxofre/uso terapêutico , Extratos Vegetais/uso terapêutico
4.
Scand J Gastroenterol ; 58(1): 25-33, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35996928

RESUMO

BACKGROUND AND AIMS: Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. METHODS: A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. RESULTS: In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors >90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p < 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p < 0.001), and by physicians managing >10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. CONCLUSION: TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Humanos , Fármacos Gastrointestinais/uso terapêutico , Monitoramento de Medicamentos/métodos , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Países Escandinavos e Nórdicos , Compostos de Enxofre/uso terapêutico , Produtos Biológicos/uso terapêutico
5.
Front Endocrinol (Lausanne) ; 13: 937956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187121

RESUMO

The progressive decline of bone mass and the deterioration of bone microarchitecture are hallmarks of the bone aging. The resulting increase in bone fragility is the leading cause of bone fractures, a major cause of disability. As the frontline pharmacological treatments for osteoporosis suffer from low patients' adherence and occasional side effects, the importance of diet regimens for the prevention of excessive bone fragility has been increasingly recognized. Indeed, certain diet components have been already associated to a reduced fracture risk. Organosulfur compounds are a broad class of molecules containing sulfur. Among them, several molecules of potential therapeutic interest are found in edible plants belonging to the Allium and Brassica botanical genera. Polysulfides derived from Alliaceae and isothiocyanates derived from Brassicaceae hold remarkable nutraceutical potential as anti-inflammatory, antioxidants, vasorelaxant and hypolipemic. Some of these effects are linked to the ability to release the gasotrasmitter hydrogen sulfide (H2S). Recent preclinical studies have investigated the effect of organosulfur compounds in bone wasting and metabolic bone diseases, revealing a strong potential to preserve skeletal health by exerting cytoprotection and stimulating the bone forming activity by osteoblasts and attenuating bone resorption by osteoclasts. This review is intended for revising evidence from preclinical and epidemiological studies on the skeletal effects of organosulfur molecules of dietary origin, with emphasis on the direct regulation of bone cells by plant-derived polysulfides, glucosinolates and isothiocyanates. Moreover, we highlight the potential molecular mechanisms underlying the biological role of these compounds and revise the importance of the so-called 'H2S-system' on the regulation of bone homeostasis.


Assuntos
Sulfeto de Hidrogênio , Dieta , Glucosinolatos , Homeostase , Humanos , Sulfeto de Hidrogênio/metabolismo , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Sulfetos , Enxofre , Compostos de Enxofre/uso terapêutico , Vasodilatadores/uso terapêutico
6.
BMJ Open ; 12(12): e060753, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36600415

RESUMO

BACKGROUND: Halitosis is defined as a foul odour emitted from the oral cavity. Many interventions have been used to control halitosis from mouthwashes to chewing gums. Probiotics have been reported as an alternative method to alleviate halitosis. OBJECTIVE: The present study aimed to investigate the effect of probiotics on halitosis from a time perspective. DESIGN AND METHODS: This is a meta-analysis study performed in indexed databases up to February 2021. Randomised controlled trials that compared the effects of probiotics and placebo on primary outcomes (organoleptic (OLP) scores and volatile sulfur compound (VSC) levels) and secondary outcomes (tongue coating scores (TCS) and plaque index (PI)) were included. Data extraction and quality assessment were conducted independently by two reviewers. Publication bias and leave-one-out analyses were performed. RESULTS: The standardised mean difference (SMD) and 95% CI were calculated to synthesise data. The data were subgrouped and analysed in the short term (≤4 weeks) and long term (>4 weeks) based on the follow-up time. Seven articles were included in this meta-analysis. The primary outcomes, OLP scores (SMD=-0.58; 95% CI -0.87 to -0.30, p<0.0001) and VSC levels (SMD=-0.26; 95% CI -0.51 to -0.01, p=0.04), both decreased significantly in the probiotics group compared with the placebo group in the short term. However, a significant reduction was observed only in OLP scores (SMD=-0.45; 95% CI -0.85 to -0.04, p=0.03) in the long term. No significant differences were observed in secondary outcomes. There was no evidence of publication bias. The leave-one-out analysis confirmed that the pooled estimate was stable. CONCLUSIONS: According to the results of this work, it seems that probiotics (eg, Lactobacillus salivarius, Lactobacillus reuteri, Streptococcus salivarius and Weissella cibaria) may relieve halitosis in the short term (≤4 weeks). The results of the biased assessment, limited data and heterogeneity of the clinical trials included might reduce the reliability of the conclusions.


Assuntos
Halitose , Probióticos , Humanos , Halitose/tratamento farmacológico , Reprodutibilidade dos Testes , Antissépticos Bucais/uso terapêutico , Boca , Compostos de Enxofre/análise , Compostos de Enxofre/uso terapêutico , Probióticos/uso terapêutico
7.
Bioorg Chem ; 112: 104889, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33915460

RESUMO

The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (Mpro) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 Mpro by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC50) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074-0.91 µM. Notably, the molecules containing furane substituent displayed higher inhibition against Mpro, followed by Ebselen 1i (IC50 = 0.074 µM) and Ebsulfur 2k (IC50 = 0.11 µM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to Mpro, while molecular docking suggested that 2k formed an SS bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of Mpro to combat COVID-19.


Assuntos
Antivirais/metabolismo , Azóis/metabolismo , Compostos Organosselênicos/metabolismo , SARS-CoV-2/metabolismo , Compostos de Enxofre/metabolismo , Proteínas da Matriz Viral/metabolismo , Antivirais/química , Antivirais/uso terapêutico , Azóis/química , Azóis/uso terapêutico , Sítios de Ligação , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico , Transferência Ressonante de Energia de Fluorescência , Humanos , Concentração Inibidora 50 , Isoindóis , Cinética , Simulação de Acoplamento Molecular , Compostos Organosselênicos/química , Compostos Organosselênicos/uso terapêutico , SARS-CoV-2/isolamento & purificação , Relação Estrutura-Atividade , Compostos de Enxofre/química , Compostos de Enxofre/uso terapêutico , Proteínas da Matriz Viral/antagonistas & inibidores , Proteínas da Matriz Viral/genética , Tratamento Farmacológico da COVID-19
8.
Acta Pharmacol Sin ; 42(1): 120-131, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32541922

RESUMO

Sirtuin 6 (SIRT6), a member of the sirtuin family, is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that is involved in various physiological and pathological processes. SIRT6 is generally downregulated and linked to tumorigenesis in non-small cell lung carcinoma (NSCLC), thus regarded as a promising therapeutic target of NSCLC. In this study, we investigated whether MDL-800, an allosteric activator of SIRT6, exerted antiproliferation effect against NSCLC cells in vitro and in vivo. We showed that MDL-800 increased SIRT6 deacetylase activity with an EC50 value of 11.0 ± 0.3 µM; MDL-800 (10-50 µM) induced dose-dependent deacetylation of histone H3 in 12 NSCLC cell lines. Treatment with MDL-800 dose dependently inhibited the proliferation of 12 NSCLC cell lines with IC50 values ranging from 21.5 to 34.5 µM. The antiproliferation effect of MDL-800 was significantly diminished by SIRT6 knockout. Treatment with MDL-800 induced remarkable cell cycle arrest at the G0/G1 phase in NSCLC HCC827 and PC9 cells. Furthermore, MDL-800 (25, 50 µM) enhanced the antiproliferation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in osimertinib-resistant HCC827 and PC9 cells as well as in patient-derived primary tumor cells, and suppressed mitogen-activated protein kinase (MAPK) pathway. In HCC827 cell-derived xenograft nude mice, intraperitoneal administration of MDL-800 (80 mg · kg-1 · d-1, for 14 days) markedly suppressed the tumor growth, accompanied by enhanced SIRT6-dependent histone H3 deacetylation and decreased p-MEK and p-ERK in tumor tissues. Our results provide the pharmacological evidence for future clinical investigation of MDL-800 as a promising lead compound for NSCLC treatment alone or in combination with EGFR-TKIs.


Assuntos
Antineoplásicos/uso terapêutico , Benzoatos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Sirtuínas/antagonistas & inibidores , Compostos de Enxofre/uso terapêutico , Acetilação/efeitos dos fármacos , Acrilamidas/farmacologia , Afatinib/farmacologia , Compostos de Anilina/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Gefitinibe/farmacologia , Histonas/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Pharmacol Ther ; 216: 107687, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32966837

RESUMO

Owing to the prevalence of chronic inflammation and its related disorders, there is a demand for novel therapeutic agents capable of preventing or suppressing inflammation. Natural products (NPs) are well established as an important resource for drug development and provide an almost infinite array of molecular entities. Sulfur-containing NPs (i.e., NPs containing one or more sulfur atoms) are abundant throughout nature, from bacteria to animals. The aim of this review was to survey the emerging evidence on role of sulfur-containing NPs, such as glutathione, garlic-derived sulfur compounds, Epipolythiodioxopiperazines (EPTs), Isothiocyanates (ITCs), and Ergothioneine (EGT), in the control of inflammation and to determine the possible underlying mechanisms. A discussion of how hydrogen sulfide (H2S), an endogenous gaseous signaling molecule, links sulfur-containing NPs and their anti-inflammatory action is also performed. This review may help to further the development of sulfur-based compounds by providing a guide for structure-activity relationship-based modification for use in modern medicinal chemistry. However, as this field is still in its infancy, the review is concluded by an overview of the progression of these promising entities as therapeutic agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Inflamação/tratamento farmacológico , Compostos de Enxofre/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Produtos Biológicos/efeitos adversos , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Transdução de Sinais , Compostos de Enxofre/efeitos adversos
10.
Molecules ; 25(17)2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32825600

RESUMO

The broad spectrum of the mechanism of action of immune-boosting natural compounds as well as the complex nature of the food matrices make researching the health benefits of various food products a complicated task. Moreover, many routes are involved in the action of most natural compounds that lead to the inhibition of chronic inflammation, which results in a decrease in the ability to remove a pathogen asymptomatically and is connected to various pathological events, such as cancer. A number of cancers have been associated with inflammatory processes. The current review strives to answer the question of whether plant-derived sulfur compounds could be beneficial in cancer prevention and therapy. This review focuses on the two main sources of natural sulfur compounds: alliaceous and cruciferous vegetables. Through the presentation of scientific data which deal with the study of the chosen compounds in cancer (cell lines, animal models, and human studies), the discussion of food processing's influence on immune-boosting food content is presented. Additionally, it is demonstrated that there is still a need to precisely demonstrate the bioavailability of sulfur-containing compounds from various types of functional food, since the inappropriate preparation of vegetables can significantly reduce the content of beneficial sulfur compounds. Additionally, there is an urgent need to carry out more epidemiological studies to reveal the benefits of several natural compounds in cancer prevention and therapy.


Assuntos
Glucosinolatos/uso terapêutico , Inflamação/prevenção & controle , Neoplasias/prevenção & controle , Extratos Vegetais/uso terapêutico , Plantas/química , Compostos de Enxofre/uso terapêutico , Animais , Humanos
11.
Antioxid Redox Signal ; 33(14): 1010-1045, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-32370538

RESUMO

Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H2S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H2S/SS in blood and/or tissues, and are amenable to treatment by H2S supplementation, development of safe and efficacious H2S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ring-substituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H2S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H2S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H2S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H2S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H2S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new "supramolecular tuning" paradigm.


Assuntos
Sulfeto de Hidrogênio/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Compostos de Enxofre/química , Compostos de Enxofre/farmacologia , Animais , Fenômenos Químicos , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Imunomodulação/efeitos dos fármacos , Estrutura Molecular , Pró-Fármacos/uso terapêutico , Espécies Reativas de Oxigênio , Células-Tronco/efeitos dos fármacos , Relação Estrutura-Atividade , Sulfetos , Compostos de Enxofre/uso terapêutico
12.
Curr Org Synth ; 17(3): 192-210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32091342

RESUMO

BACKGROUND: Sulfur-containing compounds represent an important class of chemical compounds due to their wide range of biological and pharmaceutical properties. Moreover, sulfur-containing compounds may be applied in other fields, such as biological, organic, and materials chemistry. Several studies on the activities of sulfur compounds have already proven their anti-inflammatory properties and use to treat diseases, such as Alzheimer's, Parkinson's, and HIV. Moreover, examples of sulfur-containing compounds include dapsone, quetiapine, penicillin, probucol, and nelfinavir, which are important drugs with known activities. OBJECTIVE: This review will focus on the synthesis and application of some sulfur-containing compounds used to treat several diseases, as well as promising new drug candidates. CONCLUSION: Due to the variety of compounds containing C-S bonds, we have reviewed the different synthetic routes used toward the synthesis of sulfur-containing drugs and other compounds.


Assuntos
Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/uso terapêutico , Compostos de Enxofre/síntese química , Compostos de Enxofre/uso terapêutico , Animais , Humanos
13.
Cells ; 8(11)2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671675

RESUMO

Liver fibrosis is a pathophysiologic process involving the accumulation of extracellular matrix proteins as collagen deposition. Advanced liver fibrosis can evolve in cirrhosis, portal hypertension and often requires liver transplantation. At the cellular level, hepatic fibrosis involves the activation of hepatic stellate cells and their transdifferentiation into myofibroblasts. Numerous pro-fibrogenic mediators including the transforming growth factor-ß1, the platelet-derived growth factor, endothelin-1, toll-like receptor 4, and reactive oxygen species are key players in this process. Knowledge of the cellular and molecular mechanisms underlying hepatic fibrosis development need to be extended to find novel therapeutic strategies. Antifibrotic therapies aim to inhibit the accumulation of fibrogenic cells and/or prevent the deposition of extracellular matrix proteins. Natural products from terrestrial and marine sources, including sulfur-containing compounds, exhibit promising activities for the treatment of fibrotic pathology. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans are largely unknown. This review aims to provide a reference collection on experimentally tested natural anti-fibrotic compounds, with particular attention on sulfur-containing molecules. Their chemical structure, sources, mode of action, molecular targets, and pharmacological activity in the treatment of liver disease will be discussed.


Assuntos
Produtos Biológicos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Compostos de Enxofre/uso terapêutico , Animais , Humanos
14.
Curr Gastroenterol Rep ; 20(11): 53, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30267281

RESUMO

PURPOSE OF REVIEW: The increased use of biologic agents over the past two decades has led to a reappraisal of the role of the immunomodulators (thiopurines and methotrexate) in the treatment of inflammatory bowel disease. The purpose of this review is to summarize recent data on the use of thiopurines and methotrexate either as monotherapy or as part of combination therapy with biologic agents. RECENT FINDINGS: Recent studies have addressed the need for concomitant immunomodulatory therapy in treatment-naïve patients starting anti-TNF-α therapy, the appropriate dose of the immunomodulator in this setting, the minimum duration of combination therapy, and the possible mechanisms by which immunomodulators enhance the effectiveness of anti-TNF-α agents. Little is known about the role of immunomodulators in combination with agents belonging to other classes of biologic therapies. Recent studies have shown that methotrexate is not effective in inducing or maintaining remission in ulcerative colitis. Finally, several studies have broadened our understanding of the infection and malignancy risks of the immunomodulators. Immunomodulators continue to have a place in the treatment of inflammatory bowel disease. However, with the ever-increasing list of biologic agents, properly positioning the immunomodulators within the overall therapeutic scheme is a complicated task. In order to optimize outcomes, each patient requires an individualized approach, which takes into account risks, benefits, cost, alternatives, and patient preferences.


Assuntos
Fármacos Gastrointestinais/administração & dosagem , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Metotrexato/administração & dosagem , Purinas/administração & dosagem , Compostos de Enxofre/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/administração & dosagem , Fatores Biológicos/administração & dosagem , Fatores Biológicos/uso terapêutico , Quimioterapia Combinada , Fármacos Gastrointestinais/uso terapêutico , Humanos , Fatores Imunológicos/administração & dosagem , Mercaptopurina/administração & dosagem , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Purinas/uso terapêutico , Compostos de Enxofre/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
15.
Photodiagnosis Photodyn Ther ; 24: 7-14, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30144532

RESUMO

Due to their many unique properties, graphene quantum dots (GQDs) have attracted much attention and are a promising material with potential applications in many fields. One application of GQDs is as a photodynamic therapy agent that generates singlet oxygen. In this work, GQDs were grown by focusing nanosecond laser pulses into benzene and then were later combined with methylene blue (MB) and used to eradicate the Gram-negative bacteria, Escherichia coli, and Gram-positive bacteria, Micrococcus luteus. Theoretical calculation of pressure evolution was calculated using the standard finite difference method. Detailed characterization was performed with transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), UV-vis (UV-vis), and photoluminescence (PL) spectra. Furthermore, MB-GQD singlet oxygen generation was investigated by measuring the rate of 9,10-anthracenediyl-bis(methylene) dimalonic acid photobleaching. Combining MB with GQDs caused enhanced singlet oxygen generation. Our results show that the MB-GQD combination efficiently destroys bacteria. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to determine if GQDs in dark conditions caused human cellular side-effects and affected cancer and noncancer cellular viability. We found that even high concentrations of GQDs do not alter viability under dark conditions. These results suggest that the MB-GQD combination is a promising form of photodynamic therapy.


Assuntos
Grafite/química , Terapia com Luz de Baixa Intensidade/métodos , Azul de Metileno/uso terapêutico , Pontos Quânticos/uso terapêutico , Oxigênio Singlete/agonistas , Compostos de Enxofre/uso terapêutico , Sobrevivência Celular/efeitos da radiação , Lasers de Estado Sólido , Azul de Metileno/administração & dosagem , Pontos Quânticos/administração & dosagem , Compostos de Enxofre/administração & dosagem
16.
mBio ; 8(5)2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28874472

RESUMO

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S. aureus, staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of S. aureus pigment production that reduces the survival of S. aureus under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and crtN mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN). S. aureus treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in S. aureus and presents a potent and effective lead compound for the development of virulence factor-based therapy against S. aureusIMPORTANCES. aureus staphyloxanthin contributes substantially to pathogenesis by interfering with host immune clearance mechanisms, but it has little impact on ex vivo survival of the bacterium. Agents blocking staphyloxanthin production may discourage the establishment and maintenance of bacterial infection without exerting selective pressure for antimicrobial resistance. Our newly discovered CrtN inhibitor, NP16, may offer an effective strategy for combating S. aureus infections.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxirredutases/antagonistas & inibidores , Pirrolidinas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Compostos de Enxofre/farmacologia , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Humanos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Mutação , Neutrófilos/imunologia , Estresse Oxidativo , Oxirredutases/metabolismo , Pirrolidinas/química , Pirrolidinas/uso terapêutico , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/enzimologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Compostos de Enxofre/química , Compostos de Enxofre/uso terapêutico , Virulência/efeitos dos fármacos , Fatores de Virulência/biossíntese , Xantofilas/biossíntese
17.
Front Biosci (Elite Ed) ; 9(1): 67-75, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27814590

RESUMO

Ovarian cancer ranks 5th among the most common gynecologic cancers and causes the highest mortality in females. Here, we discuss the role of a group of natural products that are being used in treatment and prevention of a host of cancers including ovarian cancer. Some plants and nutraceuticals and their polyphenolic constituents such as flavones, flavonoids, and antioxidants have shown cytotoxic effects on cancer cells both in vitro and in vivo. While phytochemicals do not harm normal cells, they have been found to be cytotoxic to cancer cells by virtue of inhibition of proliferation and/or induction of apoptosis, making them ideal in cancer therapeutics or as adjunct to conventional treatment regimens.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Feminino , Humanos , Lipídeos/química , Lipídeos/uso terapêutico , Fenóis/química , Fenóis/uso terapêutico , Compostos Fitoquímicos/classificação , Compostos de Enxofre/química , Compostos de Enxofre/uso terapêutico , Terpenos/química , Terpenos/uso terapêutico
18.
J Clin Periodontol ; 43(4): 359-65, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26824613

RESUMO

AIM: To assess the effect of different stages of intervention on volatile sulphur compounds (VSCs) of periodontitis patients with halitosis, before and after non-surgical periodontal therapy. MATERIAL & METHODS: This clinical trial included 18 adults with chronic periodontitis and halitosis. After initial examination, patients received oral hygiene (OH) instructions and tongue cleaner. One week later, non-surgical periodontal therapy was completed within 48 h. Measurements were at baseline, 1 week after OH, 1 and 6 weeks post therapy. These included simplified plaque index (sPlI), probing pocket depth (PPD), bleeding on probing (BoP), Winkel Tongue Coating Index (WTCI), organoleptic scores (OLSs) of nose and mouth air and VSCs. RESULTS: sPlI, BoP, WTCI, OLS of the mouth air and VSCs showed significant differences (p < 0.05), even after 1 week of OH. A further significant decrease was determined 1 week after non-surgical therapy for WTCI, OLS (nose and mouth air) and methyl mercaptan concentration. A significant decrease, 6 weeks post therapy, was observed for sPlI, BoP, WTCI, PPD, OLS of the nose and mouth air and VSCs (p < 0.05). CONCLUSIONS: Oral hygiene and tongue cleaning improve the OLSs of the mouth air and reduce VSCs. Periodontal therapy further improves the OLSs and reduces the concentration of VSCs.


Assuntos
Periodontite Crônica/tratamento farmacológico , Halitose/tratamento farmacológico , Compostos de Enxofre/uso terapêutico , Adulto , Idoso , Animais , Índice de Placa Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Língua
19.
Belo Horizonte; s.n; 2016. 95 p. ilus.
Tese em Inglês, Português | BBO - Odontologia | ID: biblio-912324

RESUMO

OBJETIVO: O objetivo deste trabalho foi investigar as alterações dos parâmetros salivares e dos níveis dos compostos sulfurados voláteis(CSV), durante o tratamento oncológico, em pacientes com carcinoma espinocelular em cabeça e pescoço. MATERIAIS E MÉTODOS: Estudo clínico de segmento, em que 24 pacientes foram examinados em dois momentos: antes de iniciar o tratamento com radioterapia e quimioterapia e após o término das 39 sessões de radioterapia. Avaliação da presença de saburra lingual foi realizada durante o exame clínico. Os parâmetros salivares avaliados foram: fluxo salivar em repousoe estimulado os quais foram coletadas durante 05 minutos em um tubo Falcommilimetrado. Para a saliva estimulada utilizou-se o hiperboloide (instrumento de mastigação); a viscosidade pelo viscosímetro de Ostwald modificado (modelo Cannon-FrenskeRoutine); o pH foi mensurado com um pH metro digital portátil (model Checker® 1 - HI98103). A avaliação dos CSV foi feita pelo método da cromatografia gasosa utilizando Oral ChromaTM. A escala EVA foi registrada em valores de zero a dez, em relação à sensação da boca seca do paciente.Os resultados foram analisados por meio do programa SPSS versão 17.0, com nível de confiança de 95%. RESULTADOS:Os resultados mostraram que houve uma redução estatisticamente significante do fluxo salivar estimulado e em repouso (p= 0,0002 e p= 0,0005 respectivamente) e do pH (p=0,0151). Observou-se aumento significativo da viscosidade após o término do tratamento(p= 0,0420) e também um aumento da xerostomia (p <0,0001). As concentrações dos CSV não sofreram alterações ao final do tratamento. CONCLUSÃO:Estes resultados demonstraram que o tratamento oncológico provoca uma redução do fluxo salivar e do pH, aumento da viscosidade e da xerostomia. As concentrações dos CSV não sofreram alterações ao final do tratamento, mesmo ocorrendo as alterações dos parâmetros salivares


OBJECTIVE: The aim of this study was to investigate changes in salivary parameters and levels of volatile sulfur compounds (VSC) during the oncological treatment in patients with squamous cell carcinoma of the head and neck. MATERIALS AND METHODS:clinical study segmentedin which 24 patients were examined in two stages: before starting treatment with radiotherapy and chemotherapy and after the end of the 39 radiotherapy sessions. Evaluation of the presence of tongue coating was performed during clinical examination. The salivary evaluated parameters were: salivary flow at unstimulated and stimulated which were collected during 05 minutes in a graph Falcon tube. For the stimulated saliva used the hyperboloid (chewing instrument); the viscosity by viscometer Ostwald modified (Cannon-FrenskeRoutine model); pH was measured with a portable digital pH meter (model Checker® 1 - HI98103). The evaluation was made by the CSV method of gas chromatography using Oral ChromaTM. The VAS scale was recorded at values from zero to ten, with the sensation of dry mouth patients. The results were analyzed using SPSS version 17.0 with 95% confidence level. RESULTS: The results showed a statistically significant reduction in salivary flow stimulated and unstimulated (p = 0.0002 and p = 0.0005 respectively) and pH (p = 0.0151). A significant increase in viscosity after the treatment (p = 0.0420) and an increase of xerostomia (p <0.0001). The CSV concentrations did not change after treatment. CONCLUSION: These results demonstrate that cancer treatment causes a reduced salivary flow and pH, increased viscosity and xerostomia. The CSV concentrations did not change after treatment, even occurring changes in salivary parameters


Assuntos
Humanos , Masculino , Feminino , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Glândulas Salivares/anormalidades , Saliva/efeitos dos fármacos , Saliva/efeitos da radiação , Saliva/metabolismo , Compostos de Enxofre/uso terapêutico , Viscosidade
20.
Clin Ter ; 166(4): 151-7, 2015.
Artigo em Italiano | MEDLINE | ID: mdl-26378750

RESUMO

BACKGROUND AND OBJECTIVE: The chronic arthropathies currently appear to be a major cause of disability with a negative impact on quality of life and health care spending. The mud-bath therapy is a spa treatment that induces benefic effects in chronic rheumatic diseases. It has long been debated on the assumption that the mud-bath spa therapy could have adverse cardiovascular effects which often induce caution and even a contraindication to the use of this treatment in chronic arthropathies associated with cardiovascular alterations such as hypertension. The aim of this observational study was to investigate, in arthrorheumatic subjects, the effects of sulphureous mud-bath cycle on blood pressure and the possible appearance of adverse drug reaction. PATIENTS AND METHODS: 169 patients, with age range 42-86 years, suffering by chronic arthropathies were treated with sulphureous mud-bath therapy for 2 weeks. According to the arterial pressure values, measured before the spa treatment, the patients considered were divided in three groups: with normal blood pressure (NOR group); with high blood pressure, after, the latter group was divided in IPET (patients in treatment with antihypertensive drugs) and IPENT (patients not in antihypertensive therapy). The arterial pressure values, maximum and minimum, expressed in mmHg, were detected in the first (T1) - sixth (T6) and twelfth (T12) day of spa treatment. The media arterial pressure values collected before and after T1, before and after T6, before and after T12 , before T1 and after T12 were compared. The data, presented as mean±SD, were compared with the paired Student t test. A p value ≤0.05 was considered significant. RESULTS: The comparison between the mean values detected in pre and post T1, pre and post T6, pre and post T12 have showed that sulphureous mud-bath therapy induced a significant (p<0.05) reduction of arterial blood pressure values in patients suffering of chronic arthropathies with high blood pressure in antihypertensive therapy or not (IPET and IPENT groups); while in patients with normal blood pressure (NOR group) were observed modest reduction at the limit of statistical significance. Similarly, the comparison between the data detected at the end of sulphureous mud-bath therapy (post-T12) vs baseline (pre-T1) have demonstrated: in IPET and IPENT groups a significant (p<0,01) decrease of arterial blood pressure values; in NOR group very small decrease, this reduction is significant (p<0.05) only for maximum arterial pressure value. Were not observed adverse drug reaction. CONCLUSIONS: The results of our study, in according with the few data in the literature, evidenced that is possible include the sulphureous mud-bath therapy in interdisciplinary therapeutic p rotocol of patients suffering of chronic arthropathies and arterial hypertension.


Assuntos
Pressão Sanguínea , Hipertensão/terapia , Peloterapia/métodos , Doenças Reumáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Determinação da Pressão Arterial , Doença Crônica , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/complicações , Doenças Reumáticas/fisiopatologia , Compostos de Enxofre/uso terapêutico , Resultado do Tratamento
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