Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.038
Filtrar
2.
J Nat Med ; 74(2): 487-494, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006354

RESUMO

Kaempulchraols B-D (2-4), isopimara-8(9),15-diene diterpenoids isolated from Kaempferia pulchra rhizomes collected in Myanmar, were identified as potent NF-κB inhibitors. These compounds were also effective as NO inhibitory agents, with IC50 values of 47.69, 44.97, and 38.17 µM, respectively, without showing any cytotoxicity against LPS-induced RAW264.7 cells. Investigations of the mechanisms of action of 2-4 revealed that they inhibit the NF-κB-mediated transactivation of a luciferase reporter gene, IL-6 production, and COX-2 expression, with an effective dose of 25 µM. Thus, isopimarane diterpenoids are suggested to be potent inhibitors of NF-κB pathways and could be further explored as potential anti-inflammatory lead compounds.


Assuntos
Anti-Inflamatórios/uso terapêutico , Diterpenos/uso terapêutico , NF-kappa B/metabolismo , Rizoma/química , Zingiberaceae/química , Animais , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Camundongos
3.
Phytochemistry ; 171: 112234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901735

RESUMO

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.


Assuntos
Analgésicos/uso terapêutico , Diterpenos/uso terapêutico , Ericaceae/química , Glucosídeos/uso terapêutico , Dor/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Glucosídeos/química , Glucosídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Estrutura Molecular , Dor/induzido quimicamente , Medição da Dor , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-Atividade
4.
J Nat Med ; 74(2): 434-440, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31960210

RESUMO

The predominant feature of type 2 diabetes is insulin resistance. Identifying a drug able to reduce insulin resistance is an urgent requirement. ent-3α-Formylabieta-8(14),13(15)-dien-16,12ß-olide had been identified as a new diterpene derivative which showed anticancer activity. This study explores the hypoglycemic effect of ent-3α-formylabieta-8(14),13(15)-dien-16,12ß-olide and studied its mechanism. The insulin response of HepG2 cells following ent-3α-formylabieta-8(14),13(15)-dien-16,12ß-olide treatment, as a model for liver cancer cells, was assessed. The results demonstrated that hyperglycemia resulted in a significant increase in the levels of insulin receptor substrate-1 (IRS-1) serine phosphorylation and decrease in Akt phosphorylation. High glucose also inhibited the phosphorylation of insulin-dependent GSK3ß. ent-3α-Formylabieta-8(14),13(15)-dien-16,12ß-olide treatment improved the effect of insulin on the phosphorylation of IRS-1 Ser307. In addition, this study demonstrated that the effect of ent-3α-formylabieta-8(14),13(15)-dien-16,12ß-olide was dependent on the activation of AMP-activated protein kinase. Collectively, experimental data indicated an association between insulin resistance and hyperglycemia in HepG2 cells, and that ent-3α-formylabieta-8(14),13(15)-dien-16,12ß-olide reduces IRS-1 Ser307 phosphorylation via activating AMPK, thereby decreasing the insulin signaling blockade.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diterpenos/uso terapêutico , Células Hep G2/metabolismo , Insulina/metabolismo , Diterpenos/farmacologia , Humanos , Transdução de Sinais , Transfecção
5.
Arch Dis Child Fetal Neonatal Ed ; 105(2): 123-127, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31036701

RESUMO

OBJECTIVE: To examine changes in blood pressure (BP), cardiac output (CO) and cerebral regional oxygen saturation (rScO2) with administration of premedication for neonatal intubation. DESIGN: Pilot, prospective, observational study. Oxygen saturation, heart rate, CO, rScO2 and BP data were collected. Monitoring began 5 min prior to premedication and continued until spontaneous movement. SETTING: Single-centre, level 3 neonatal intensive care unit PATIENTS: 35 infants, all gestational ages. 81 eligible infants: 66 consented, 15 refused. INTERVENTIONS: Intravenous atropine, fentanyl or morphine, ±cisatracurium MAIN OUTCOME MEASURES: BP, CO, rScO2 RESULTS: n=37 intubations. Mean gestational age and median birth weight were 31 4/7 weeks and 1511 g. After premedication, 10 episodes resulted in a BP increase from baseline and 27 in a BP decrease. Of those whose BP decreased, 17 had <20% decrease and 10 had ≥20% decrease. Those with <20% BP decrease took an average of 2.5 min to return to baseline while those with a ≥20% BP decline took an average of 15.2 min. Three did not return to baseline by 35 min. Following intubation, further declines in BP (21%-51%) were observed in eight additional cases. One infant required a bolus for persistently low BPs. CO and rScO2 changes were statistically similar between the two groups. CONCLUSION: About 30% of infants dropped their BP by ≥20% after premedication for elective intubation. These BP changes were not associated with any significant change in rScO2 or CO. More data are needed to better characterise the immediate haemodynamic changes and clinical outcomes associated with premedication.


Assuntos
Analgésicos Opioides/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Terapia Intensiva Neonatal/organização & administração , Intubação Intratraqueal/métodos , Bloqueadores Neuromusculares/uso terapêutico , Pré-Medicação/métodos , Analgésicos Opioides/administração & dosagem , Atracúrio/análogos & derivados , Atracúrio/uso terapêutico , Peso ao Nascer , Diterpenos/uso terapêutico , Quimioterapia Combinada , Feminino , Fentanila/uso terapêutico , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal/organização & administração , Masculino , Morfina/uso terapêutico , Oxigênio/sangue , Projetos Piloto , Estudos Prospectivos
7.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795079

RESUMO

This article summarizes the histories of six patients with different solid tumors treated with a new strategy based on tumor burden reduction and immune evasion as potential targets. All six patients were at a high risk of relapse and were likely to have a minimal residual disease following conventional therapy: biochemical recurrence (BCR) following radical prostatectomy (RP) (two prostate cancers patients), removal of distant metastases (one colorectal and one breast cancer), and complete response (CR) of distant metastases to conventional therapy (one breast cancer and one esophageal-gastric junction cancer). Four of the patients, two after RP and BCR, one after removal of a single pulmonary metastasis from breast cancer, and one after CR to chemotherapy of peritoneal metastases and ascites from an esophageal-gastric junction primary cancer, regularly received cycles of a new drug schedule with the aim of inhibiting immune suppression (IT). In these four patients, preliminary laboratory tests of peripheral blood suggested an interleukin (IL)-2/IL-12 mediated stimulation of cellular immune response with a concomitant decrease in vascular endothelial growth factor (VEGF) immune suppression. The fifth case was a breast cancer patient with distant metastases in CR, while receiving beta-interferon and interleukin-2 in addition to conventional hormone therapy. To date, all five patients are alive and doing well and they have been unexpectedly disease-free for 201 and 78 months following BCR, 28 months following the removal of a single pulmonary metastases, 32 months following CR to chemotherapy of peritoneal metastases and ascites, and 140 months following diagnosis of multiple bone metastases, respectively. The sixth patient, who had colorectal cancer and multiple synchronous liver metastases and underwent nine surgical interventions for metastatic disease, although not disease-free, is doing well 98 months after primary surgery. Our six cases reports can be interpreted with the hypothesis that immune manipulation and/or a concomitant low tumor burden favored their clinical outcome.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Imunossupressores/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Celecoxib/administração & dosagem , Celecoxib/uso terapêutico , Neoplasias do Colo/patologia , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Diterpenos/administração & dosagem , Diterpenos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Próstata/patologia , Carga Tumoral , Evasão Tumoral , Vitamina A/administração & dosagem , Vitamina A/análogos & derivados , Vitamina A/uso terapêutico , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/uso terapêutico
8.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878303

RESUMO

Ulcerative colitis (UC) is usually accompanied with symptoms of abdominal pain, diarrhea, and bloody stool, which impair the quality of life of patients. Previous studies have shown that Andrographis paniculata extracts, which have andrographolide (AND) as their main compound, can relieve UC symptoms in patients. The aim of the study was to investigate the alleviating effect of AND on UC using the oxazolone (OXZ)-induced UC rat model. A total of 66 healthy male Sprague Dawley rats were used to evaluate the efficacy and mechanism of AND on UC (n = 11 per group) and grouped into control, model, SASP (sulfasalazine, positive control group, 500 mg/kg), AND-L (40 mg/kg), AND-M (80 mg/kg), and AND-H (120 mg/kg). The colonic disease activity index (DAI), colon length, spleen coefficient, pathological damage, and inflammation-related cytokine and protein expression levels were used as indices for evaluation. Results showed that the AND groups had reduced DAI and mortality, and significantly improved colon length and spleen coefficient compared with the model group. Furthermore, OXZ-induced histological injury was relieved significantly after AND treatment due to an improved crypt structure and reduced infiltration of inflammatory cells. Moreover, AND inhibited myeloperoxidase (MPO) activity and the secretion of interleukin-4 (IL-4), IL-13, and tumor necrosis factor α (TNF-α). The results of the anti-inflammatory mechanism revealed that AND blocked the signal transduction by reducing IL-4/IL-13 specific binding to IL-4 receptor (IL-4R) and inhibiting the phosphorylation of the signal transducer and activator of transcription 6 (p-STAT6). In conclusion, aside from natural plants, AND may be a candidate ingredient for UC therapy.


Assuntos
Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Diterpenos/uso terapêutico , Animais , Biomarcadores/metabolismo , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/metabolismo , Diterpenos/farmacologia , Inflamação/patologia , Masculino , Oxazolona , Peroxidase/metabolismo , Ratos Sprague-Dawley , Receptores de Interleucina-4/metabolismo , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/metabolismo
9.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881712

RESUMO

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion's mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson's disease, and Alzheimer's disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.


Assuntos
Basidiomycota/química , Produtos Biológicos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Basidiomycota/metabolismo , Produtos Biológicos/química , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Transtorno Depressivo/patologia , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/uso terapêutico , Humanos , Indóis/química , Indóis/isolamento & purificação , Indóis/uso terapêutico , Micélio/química , Micélio/metabolismo , Fatores de Crescimento Neural/metabolismo
10.
Oxid Med Cell Longev ; 2019: 6138723, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687082

RESUMO

Trinitrobenzenesulfonic acid (TNBS) and dextran sodium sulfate (DSS) are commonly used to induce experimental murine ulcerative colitis (UC). Our recent study has demonstrated that a novel andrographolide derivative, AL-1, ameliorated TNBS-induced colitis in mice. However, the effect of AL-1 on DSS-induced murine colitis and the underlying mechanisms are yet unknown. In the present study, we aimed to investigate the therapeutic potential of AL-1 against DSS-induced UC in mice and to define its mechanisms of action. Oral administration of AL-1 attenuated body weight loss, reduced colon length shortening, lowered the disease activity index score, and alleviated colon histological damage. AL-1 significantly inhibited myeloperoxidase activity and suppressed immune inflammatory responses in colonic tissues. Moreover, AL-1 reversed DSS-altered expression of inflammatory cytokines in DSS-induced colitis mice. Importantly, the efficacy of 45 mg/kg of AL-1 was higher than that of 100 mg/kg of the positive control drugs 5-aminosalicylic acid and mesalazine. AL-1 decreased lipopolysaccharide-induced generation of reactive oxygen species and nitric oxide in cultured macrophages in vitro; it also reversed the altered expression of inflammatory cytokines. In both in vivo and in vitro studies, Western blot analysis revealed that AL-1 reduced the expression of phosphorylated NF-κB p65 and IκBα, downregulated the expression of iNOS and COX-2, and attenuated the expression of phosphorylated p38 mitogen-activated protein kinase (MAPK), ERK, and JNK. In conclusion, AL-1 alleviated DSS-induced murine colitis by inhibiting activation of the NF-κB and MAPK signaling pathways. Our data suggest that AL-1 could be a potential new treatment for UC.


Assuntos
Colite/tratamento farmacológico , Colite/enzimologia , Diterpenos/uso terapêutico , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Colite/sangue , Colite/induzido quimicamente , Citocinas/sangue , Sulfato de Dextrana , Modelos Animais de Doenças , Diterpenos/farmacologia , Feminino , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/sangue , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
11.
Eur J Dermatol ; 29(4): 401-408, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625920

RESUMO

BACKGROUND: The use of ingenol mebutate (IM) as a field-directed therapy over a short period of time has been shown to be effective and well tolerated in randomized Phase III trials. OBJECTIVES: To assess the efficacy and patient-reported outcomes for IM as treatment for actinic keratosis (AK) under daily "real-life" practice conditions. MATERIALS AND METHODS: A total of 826 adult patients with AK were enrolled by 292 dermatologists in Germany in a prospective, open, non-interventional, non-controlled, multicentre study. All patients were treated with IM and followed for eight weeks. RESULTS: The mean number of clinically visible AK lesions decreased significantly from 7.1±6.8 to 2.8±4.5 (p<0.0001). Most dermatologists (79.0%) rated global efficacy of IM as "very good"/"good" and 82.6% of the patients were "very satisfied" or "rather satisfied" with the efficacy of IM. Patient-reported outcomes showed greater efficacy and treatment comfort with IM compared to any last previous AK treatment with a comparable tolerability profile. Skin-related QoL data revealed a significant improvement of 50.2% after IM treatment (p<0.0001). Adverse events were reported in 7.0% of all patients, which were in most cases mild in intensity. CONCLUSION: Field-directed treatment with IM over a short period was associated with a high level of treatment satisfaction, as reported by dermatologists and patients. This observational study demonstrates the effectiveness and tolerability of IM in everyday clinical practice in addition to the known efficacy and safety obtained by randomized controlled clinical trials.


Assuntos
Diterpenos/uso terapêutico , Ceratose Actínica/diagnóstico , Ceratose Actínica/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Administração Tópica , Adulto , Diterpenos/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Seguimentos , Alemanha , Humanos , Ceratose Actínica/psicologia , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
13.
Oxid Med Cell Longev ; 2019: 2580409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612073

RESUMO

Current therapeutic approaches have a limited effect on cardiac remodeling, which is characteristic of cardiac fibrosis and myocardial hypertrophy. In this study, we examined whether Danshenol A (DA), an active ingredient extracted from the traditional Chinese medicine Radix Salviae, can attenuate cardiac remodeling and clarified the underlying mechanisms. Using the spontaneously hypertensive rat (SHR) as a cardiac remodeling model, DA ameliorated blood pressure, cardiac injury, and myocardial collagen volume and improved cardiac function. Bioinformatics analysis revealed that DA might attenuate cardiac remodeling through modulating mitochondrial dysfunction and reactive oxygen species. DA repaired the structure/function of the mitochondria, alleviated oxidative stress in the myocardium, and restored apoptosis of cardiomyocytes induced by angiotensin II. Besides, DA inhibited mitochondrial redox signaling pathways in both the myocardium and cardiomyocytes. Thus, our study suggested that DA attenuates cardiac remodeling induced by hypertension through modulating mitochondrial dysfunction and reactive oxygen species.


Assuntos
Diterpenos/uso terapêutico , Hipertensão/tratamento farmacológico , Mitocôndrias Cardíacas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Animais , Diterpenos/farmacologia , Humanos , Masculino , Ratos
14.
Eur J Med Chem ; 181: 111594, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419741

RESUMO

A series of novel acetamine phenyl pleuromutilin derivatives incorporating 2-aminothiophenol moieties into the C14 side chain were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the synthesized derivatives against three Staphylococcus aureus (MRSA ATCC 43300, ATCC 29213 and AD 3) and two Escherichia coli (ATCC 25922 and 9-1) were evaluated by the broth dilution method. Most of the synthesized derivatives displayed potent activities. Compound 27 was found to be the most active antibacterial derivative against MRSA (minimal inhibitory concentration = 0.015 µg/mL) which may lead to a promising antibacterial drug. Furthermore, compound 27 displayed more rapid bactericidal kinetic than tiamulin in in vitro time-kill studies and possessed a longer PAE than tiamulin against MRSA. The PK properties of compound 27 were then measured. The half life (t1/2), clearance rate (Cl) and the area under the plasma concentration-time curve (AUC0→∞) of compound 27 were 6.88 h, 21.64 L/h/kg and 0.48 µg h/mL, respectively. The in vivo antibacterial activities of compound 27 against MRSA were further evaluated using thigh infection model and systemic infection model. Compound 27 possessed superior antibacterial efficacy to tiamulin against MRSA infection in both model.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Compostos de Anilina/síntese química , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Animais , Antibacterianos/síntese química , Antibacterianos/uso terapêutico , Diterpenos/síntese química , Diterpenos/uso terapêutico , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos Endogâmicos ICR , Compostos Policíclicos/síntese química , Compostos Policíclicos/uso terapêutico , Infecções Estafilocócicas/microbiologia
15.
An Bras Dermatol ; 94(3): 313-319, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365660

RESUMO

BACKGROUND: Actinic keratosis (AK) represents a risk of progression to squamous cell carcinoma. Ingenol mebutate gel is a novel therapeutic option for field-directed treatment. OBJECTIVES: To evaluate the safety, tolerability and patients' perspectives, related to the therapeutic success of managing AKs on the face and scalp with ingenol mebutate gel in Brazilian individuals. METHODS: This was an observational, retrospective and descriptive study of 68 areas of actinic keratosis on the face and scalp treated with Ingenol mebutate gel involving a total of 37 patients. The drug was applied for three consecutive days on an area of of 25 cm2 and documentation was performed on baseline and days 4, 8, 15, 60 and 180. On day 4, the composite local skin reaction score was calculated. At the end, a questionnaire was applied to evaluate patients' perspectives about the treatment. RESULTS: Adherence was 100%, no serious adverse events were recorded and the mean composite local skin reaction score (standard deviation) was 8.61±4.22. The treatment was considered optimum by 75.68% of the patients. STUDY LIMITATIONS: Calculation of composite local skin reaction score performed only on the fourth day. CONCLUSIONS: Treatment with ingenol mebutate gel was considered safe and tolerable in Brazilian subjects. Patients had a maximum adherence rate and a great improvement in self-esteem. The results of this research reproduce the findings of the literature.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Diterpenos/uso terapêutico , Géis/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Brasil , Dermatoses Faciais/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatoses do Couro Cabeludo/tratamento farmacológico , Inquéritos e Questionários , Resultado do Tratamento
16.
Dermatol Clin ; 37(4): 435-441, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466584

RESUMO

Although surgical intervention remains the standard of care for nonmelanoma skin cancer, other treatment modalities have been studied and used. Nonsurgical treatment methods include cryotherapy, topical medications, photodynamic therapy, radiation therapy, Hedgehog pathway inhibitors, programmed cell death protein 1 inhibitors, and active nonintervention. Despite the favorable efficacy of surgical treatment methods, many factors, including but not limited to patient age, preference, and severity of disease, must be taken into consideration when choosing the most appropriate, patient-centered treatment approach.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Fotoquimioterapia , Radioterapia , Neoplasias Cutâneas/terapia , Administração Cutânea , Anilidas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Criocirurgia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Diclofenaco/uso terapêutico , Diterpenos/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Imiquimode/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Piridinas/uso terapêutico , Conduta Expectante
17.
Future Microbiol ; 14: 927-939, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333062

RESUMO

Despite the increasing availability of antibiotics with activity against pathogens that cause community-acquired pneumonia (CAP), CAP remains a major cause of morbidity, hospital admissions and re-admissions, and mortality. Lefamulin is a novel pleuromutilin antibiotic with potent in vitro activity against both typical and atypical CAP pathogens. In this review of the medical literature, we summarize the available information, including mounting clinical evidence, about lefamulin and its potential value in CAP.


Assuntos
Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Pneumonia/tratamento farmacológico , Compostos Policíclicos/farmacologia , Compostos Policíclicos/uso terapêutico , Tioglicolatos/farmacologia , Tioglicolatos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Diterpenos/efeitos adversos , Diterpenos/química , Humanos , Estrutura Molecular , Pneumonia/microbiologia , Compostos Policíclicos/efeitos adversos , Compostos Policíclicos/química , Subunidades Ribossômicas Maiores de Bactérias/efeitos dos fármacos , Tioglicolatos/efeitos adversos , Tioglicolatos/química , Resultado do Tratamento
18.
J Ethnopharmacol ; 243: 112078, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31301369

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron molle G. Don (Ericaceae) (RM) is a natural medicinal plant. Its root extracts have been applied in clinic and proved to be effective in chronic glomerulonephritis and rheumatoid arthritis in China. Surprising, little is understood about the key compound of RM and the exact mechanisms underlying its treatment on kidney diseases. In this study, we will explore whether rhodojaponin II (R-II), as the important compound of RM, also exerts the major effect. MATERIALS AND METHODS: Mouse model of focal segmental glomerulosclerosis was induced by single dose of adriamycin injection. Induced adriamycin nephropathy (ADRN) mice were treated individually with RM root extract (5 mg/kg, n = 5), RM root extract (60 mg/kg, n = 5), R-II (0.04 mg/kg, n = 6) or captopril (30 mg/kg, n = 5) for five weeks. Podocyte marker (nephrin and podocin) expressions were examined by immunohistochemical staining and Western Blot analysis. Fibronectin level was evaluated by immunohistochemical staining and Western Blot analysis. Interstitial infiltrated inflammatory cells (CD4+ T cells, CD8+ T cells, and CD68+ macrophages) were examined with immunohistochemical staining. The expressions of NF-ĸB p-p65 and TGF-ß1/Smad pathway associated key proteins, such as TGF-ß1, Smad3, phosphorylated-Smad3 (p-Smad3), and Smad7, were analyzed respectively by Western Blot analysis. RESULTS: RM root extract (5 mg/kg) and its important compound R-II (0.04 mg/kg) significantly ameliorated proteinuria, podocyte injury, and glomerulosclerosis, meanwhile, they hampered interstitial fibrosis in mice with ADRN. R-II significantly reduced NF-ĸB p65 phosphorylation, interstitial infiltrated CD4+ T cells, CD8+ T cells, and CD68+ macrophages, at the same time, down-regulated TGF-ß1 and p-Smad3 protein expressions in mice with ADRN. CONCLUSION: RM root extract, R-II, could effectively ameliorate proteinuria and kidney injury in ADRN, related to its anti-inflammatory effects, as well as suppression of TGF-ß1/Smad signaling pathway.


Assuntos
Anti-Inflamatórios , Diterpenos , Glomerulosclerose Segmentar e Focal , Extratos Vegetais , Proteinúria , Rhododendron , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Doxorrubicina , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Proteinúria/induzido quimicamente , Proteinúria/tratamento farmacológico , Proteinúria/metabolismo , Proteinúria/patologia , Transdução de Sinais/efeitos dos fármacos
19.
Phytomedicine ; 63: 153009, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301540

RESUMO

BACKGROUND: Considering the limitations of conventional western treatment for community-acquired pneumonia (CAP) and the extensive exploration of Chinese herbal injections (CHIs), systematically and critically evaluating the efficacy of CHIs in the treatment of CAP is necessary. PURPOSE: This study constructed a network meta-analysis (NMA) to investigate the efficacy of CHIs (including the Reduning injection (RDN), Yanhuning injection (YHN), Xiyanping injection (XYP), and Tanreqing injection (TRQ)) combined with Western medicine (WM) and WM alone in CAP. METHODS: A literature review was conducted in several databases from inception to June 2018. The quality of the included studies was assessed by the Cochrane risk of bias tool and modified Jadad scale. Data were analyzed by STATA 13.0 and WinBUGS 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Clustering analysis was utilized to compare the effect of CHIs between two different outcomes. RESULTS: A total of 47 eligible randomized controlled trials involving 4713 patients and 4 CHIs were included. The results of the NMA showed that RDN, YHN, XYP and TRQ combined with WM significantly improved treatment performance compared to WM alone. YHN+WM had obvious superiorities in the clinical effective rate, time for the disappearance of cough and the level of C-reactive protein. TRQ+WM was the most advantageous in shortening the time for defervescence and the average hospitalization time. XYP+WM was shown to reduce the time for the disappearance of lung rales best. Sixteen articles reported adverse drug reactions/adverse drug events (ADRs/ADEs) in detail, and 17 articles reported that there were no obvious ADRs/ADEs. CONCLUSION: This NMA showed that using CHIs in combination with WM improved treatment performance and could be beneficial for patients with CAP compared to using WM alone. Thereinto, YHN+WM showed a preferable improvement on patients with CAP when unified considering the clinical effective rate and other outcomes. As for safety, more evidence is needed to support this hypothesis.


Assuntos
Infecções Comunitárias Adquiridas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pneumonia/tratamento farmacológico , Teorema de Bayes , Tosse/tratamento farmacológico , Diterpenos/administração & dosagem , Diterpenos/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Injeções , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Neurochem Res ; 44(8): 1977-1985, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31236795

RESUMO

Tripterygium Wilfordii Hook F has been exploited as a treatment for several diseases due to its neuroprotective, anti-tumor, and anti-inflammatory effects. Triptolide is one of its key bioactive compounds. Currently, the role of triptolide in cognitive dysfunction remains unclear. Here, the role of triptolide on cognitive dysfunction was investigated using chronic cerebral hypoperfusion-induced vascular dementia (VD) rat model. SD rats were administrated with Triptolide (5 µg/kg) for 6 weeks after undergoing permanent bilateral common carotid artery occlusion. The results show that triptolide treatment conferred neuroprotective effects in VD rats. Intraperitoneal injection of triptolide attenuated oxidative stress, learning and memory deficits, and neuronal apoptosis in the hippocampi. Moreover, triptolide enhanced the expression of SIRT1, PGC-1α, ZO-1, Claudin-5, and decreased the serum levels of NSE and S100B significantly. It also improved CCH-induced learning and memory deficits, and this is attributed to its capacity to promote SIRT1/PGC-1α signaling, confer antioxidant effects, and inhibit neuronal apoptosis. These findings indicate that triptolide may be an effective therapeutic agent for vascular cognitive dysfunction.


Assuntos
Demência Vascular/prevenção & controle , Diterpenos/uso terapêutico , Nootrópicos/uso terapêutico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fenantrenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Claudina-5/metabolismo , Compostos de Epóxi/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Memória Espacial/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA