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1.
Trials ; 21(1): 785, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928313

RESUMO

OBJECTIVES: 1- To compare the effectiveness of 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline and a novel solution Neem extract (Azardirachta indica) in reducing intra-oral viral load in COVID-19 positive patients. 2- To determine the salivary cytokine profiles of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL- 17 among COVID-19 patients subjected to 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline or Neem extract (Azardirachta indica) based gargles. TRIAL DESIGN: This will be a parallel group, quadruple blind-randomised controlled pilot trial with an add on laboratory based study. PARTICIPANTS: A non-probability, purposive sampling technique will be followed to identify participants for this study. The clinical trial will be carried out at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. The viral PCR tests will be done at main AKUH clinical laboratories whereas the immunological tests (cytokine analysis) will be done at the Juma research laboratory of AKUH. The inclusion criteria are laboratory-confirmed COVID-19 positive patients, male or female, in the age range of 18-65 years, with mild to moderate disease, already admitted to the AKUH. Subjects with low Glasgow coma score, with a history of radiotherapy or chemotherapy, who are more than 7 days past the onset of COVID- 19 symptoms, or intubated or edentulous patients will be excluded. Patients who are being treated with any form of oral or parenteral antiviral therapy will be excluded, as well as patients with known pre-existing chronic mucosal lesions such as lichen planus. INTERVENTION AND COMPARATOR: Group A (n=10) patients on 10 ml gargle and nasal lavage using 0.2% Povidone-Iodine (Betadiene® by Aviro Health Inc./ Pyodine® by Brooks Pharma Inc.) for 20-30 seconds, thrice daily for 6 days. Group B (n=10) patients will be subjected to 10 ml gargle and nasal lavage using 1% Hydrogen peroxide (HP® by Karachi Chemicals Products Inc./ ActiveOxy® by Boumatic Inc.) for 20-30 seconds, thrice daily for 6 days. Group C will comprised of (n=10) subjects on 10ml gargle and nasal lavage using Neem extract solution (Azardirachta indica) formulated by Karachi University (chemistry department laboratories) for 20-30 seconds, thrice daily for 6 days. Group D (n=10) patients will use 2% hypertonic saline (Plabottle® by Otsuka Inc.) gargle and nasal lavage for a similar time period. Group E (n=10) will serve as positive controls. These will be given simple distilled water gargles and nasal lavage for 20-30 seconds, thrice daily for six days. For nasal lavage, a special douche syringe will be provided to each participant. Its use will be thoroughly explained by the data collection officer. After each use, the patient is asked not to eat, drink, or rinse their mouth for the next 30 minutes. MAIN OUTCOMES: The primary outcome is the reduction in the intra-oral viral load confirmed with real time quantitative PCR. RANDOMISATION: The assignment to the study group/ allocation will be done using the sealed envelope method under the supervision of Clinical Trial Unit (CTU) of Aga Khan University, Karachi, Pakistan. The patients will be randomised to their respective study group (1:1:1:1:1 allocation ratio) immediately after the eligibility assessment and consent administration is done. BLINDING (MASKING): The study will be quadruple-blinded. Patients, intervention provider, outcome assessor and the data collection officer will be blinded. The groups will be labelled as A, B, C, D or E. The codes of the intervention will be kept in lock & key at the CTU and will only be revealed at the end of study or if the study is terminated prematurely. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. The present study will serve as a pilot trial. We intend to study 50 patients in five study groups with 10 patients in each study group. For details, please refer to Fig. 1 for details. TRIAL STATUS: Protocol version is 7.0, approved by the department and institutional ethics committees and clinical trial unit of the university hospital. Recruitment is planned to start as soon as the funding is sanctioned. The total duration of the study is expected to be 6 months i.e. August 2020-January 2021. TRIAL REGISTRATION: This study protocol was registered at www.clinicaltrials.gov on 10 April 2020 NCT04341688 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). Fig. 1 Flow diagram of study-participants' timeline.


Assuntos
Azadirachta , Betacoronavirus , Infecções por Coronavirus , Peróxido de Hidrogênio/administração & dosagem , Pandemias , Extratos Vegetais/administração & dosagem , Pneumonia Viral , Povidona-Iodo/administração & dosagem , Solução Salina Hipertônica/administração & dosagem , Carga Viral , Adulto , Anti-Infecciosos Locais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Feminino , Hospitalização , Humanos , Masculino , Monitorização Imunológica/métodos , Antissépticos Bucais/administração & dosagem , Lavagem Nasal/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carga Viral/efeitos dos fármacos , Carga Viral/métodos
2.
Trials ; 21(1): 790, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933552

RESUMO

OBJECTIVES: We investigate the effects of Licorice (Glycyrrhiza glabra L.) root extract, an anti-inflammatory natural medicine, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in patients with confirmed COVID-19 that are moderately ill. TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: Both male and female patients with ≥18 years of age (≥ 35 kg of weight), admitted at the Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas for treatment, screened for the following criteria. INCLUSION CRITERIA: 1. Confirmed diagnosis of SARS-CoV-2 infection (via polymerase chain reaction [PCR] and/or antibody test). 2. Presenting as moderate COVID-19 pneumonia (via chest computed tomography (CT) and/or X-ray) requiring hospitalization. 3. Hospitalized ≤48 hours. 4. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs. 4. Treatment with Investigational and antiviral therapy in a clinical study within one month before randomization. 5. History of allergy to Licorice. 6. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19 along with a Licorice-based herbal preparation (D-Reglis ®, Irandarouk Pharmaceutical Company, Iran) at a dose of 760 mg three times a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The recovery rate of clinical symptoms, including fever, dry cough, and tiredness, as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein, are evaluated as primary outcomes within seven days of randomization. Time to improvement of clinical and paraclinical features and length of stay in a hospital, along with the incidence of adverse reactions are also evaluated as the secondary outcomes within seven days of randomization. RANDOMIZATION: An electronic table of random numbers will be used to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the simple randomization method. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is "IRCT20200506047323N2", https://www.irct.ir/trial/47990 . The registration date is 31 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Infecções por Coronavirus , Glycyrrhiza , Pandemias , Extratos Vegetais , Raízes de Plantas , Pneumonia Viral , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Monitoramento de Medicamentos/métodos , Feminino , Hospitalização , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Am J Chin Med ; 48(6): 1409-1433, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907360

RESUMO

Scutellaria baicalensis (SB), a herbal medicine, is commonly used to treat metabolic diseases, while Metformin (MF) is a widely used drug for type 2 diabetes. The purpose of this study was to investigate whether co-treatment of SB with MF could produce a potential therapeutic effect on high-fat and high-fructose diet (HFFD)-induced metabolic dysregulation. First, we optimized the dose of SB (100, 200, 400, and 800[Formula: see text]mg/kg) with MF (200[Formula: see text]mg/kg) in HFFD-induced C57BL6J mice. Next, the optimized dose of SB (400[Formula: see text]mg/kg) was co-administered with MF (50, 100, and 200[Formula: see text]mg/kg) in a similar animal model to find the effective combinations of SB and MF. Metabolic markers were determined in serum and tissues using different assays, histology, gene expression, and gut microbial population. The SB and MF co-treatment significantly decreased the body, liver, and VAT weights. The outcome of OGTT was improved, and the fasting insulin, HbA1c, TG, TC, LDL-c, AST, and ALT were decreased, while HDL-c was significantly increased. Histological analyses revealed maintained the integrity of liver, adipose tissue, and intestine prevented lipid accumulation in the liver and intestine and combated neuronal damage in the brain. Importantly, controlled the expression of PPAR[Formula: see text], and IL-6 genes in the liver, and expression of BDNF, Glut1, Glut3, and Glut4 genes in the brain. Treatment-specific gut microbial segregation was observed in the PCA chart. Our findings indicate that SB and MF co-treatment is an effective therapeutic approach for HFFD-induced metabolic dysregulation which is operated through the gut-liver-brain axis.


Assuntos
Encéfalo/metabolismo , Microbioma Gastrointestinal , Fígado/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Metformina/administração & dosagem , Metformina/farmacologia , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Quimioterapia Combinada , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/microbiologia , Camundongos Endogâmicos C57BL , PPAR gama/genética , PPAR gama/metabolismo
4.
Medicine (Baltimore) ; 99(38): e22228, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957363

RESUMO

INTRODUCTION: Cancer is the second leading cause of death, and the burden of cancer continues to grow globally. Research on the efficacy of combined administration of herbal medicine and anticancer drugs is also increasing. SH003 is a new herbal medicine composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. SH003 alone up to 4800 mg daily was found to be safe. Preclinical studies have shown SH003 to have a synergistic effect with coadministration of anticancer drugs. This study aimed to determine the maximum tolerated dose of SH003 combined with docetaxel in patients with lung or breast cancer. METHODS: This is an open-label, dose-escalation study to evaluate the safety of SH003 combined with docetaxel. Patients with lung or breast cancer will be recruited. The participants will be divided into 3 groups based on SH003 daily dose (2400, 3600, and 4800 mg); the medication will be taken orally for 21 days. The traditional 3 + 3 design will be adopted for the dose escalation. Dose-limiting toxicities are defined as grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events. The highest dose at which no more than 1 of the 6 patients experience dose-limiting toxicity will be determined as the maximum tolerated dose of SH003 combined with docetaxel. DISCUSSION: This study investigates the safety of SH003 when combined with docetaxel. The results of this study will provide a safe dose range for conducting therapeutic exploratory trials. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04360317.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Ensaios Clínicos Fase I como Assunto , Humanos , Fitoterapia
5.
J Oleo Sci ; 69(8): 929-939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759551

RESUMO

Glucosylceramide (GlcCer), a major sphingolipid in plants and fungi, is known to have food functions, such as preventing intestinal impairment and enhancing the moisture content of skin. This study investigated the influence of fermentation on the composition and function of lipophilic components containing GlcCer in plant-based foods; we compared the effects of ethanol extracts from sake rice (SR) and sake lees (SL) on colon impairment in mice. GlcCer and ceramide (Cer) levels in SL were much higher than those in SR, and GlcCer in SL contained 9-methyl-trans-4,trans-8-sphingadienine as a fungi-specific sphingoid base. 1,2-dimethylhydrazine (DMH) treatment markedly increased the formation of aberrant crypt foci (ACF) and the levels of TNF-α and lipid oxidation in mice colons. However, dietary SR or SL significantly suppressed these DMH-induced changes, and SR demonstrated stronger effects than SL. In addition, dietary SR or SL suppressed the expression of apoptotic and anti-apoptotic proteins induced by DMH treatment. This study suggests that SR or SL intake could reduce colon ACF formation via the suppression of inflammation and oxidation-induced cell cycle disturbances. When compared to SR, the weaked effects of SL rich in GlcCer may be the result of the changes in sphingolipid composition (sphingoid base and Cer) and differences in the concentration of other bioactive compounds produced or digested during fermentation.


Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Neoplasias do Colo/prevenção & controle , Glucosilceramidas/análise , Glucosilceramidas/farmacologia , Oryza/química , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Vinho/análise , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Administração Oral , Animais , Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Etanol , Feminino , Fermentação , Glucosilceramidas/administração & dosagem , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
6.
Med Hypotheses ; 143: 110150, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763660

RESUMO

COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Estrogênios/fisiologia , Hemostáticos/uso terapêutico , Mucosite/tratamento farmacológico , Pandemias , Fitoestrógenos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Pneumonia Viral/complicações , Receptor PAR-1/antagonistas & inibidores , Administração Tópica , Distribuição por Idade , Anti-Inflamatórios/administração & dosagem , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Reposicionamento de Medicamentos , Endotélio Vascular/efeitos dos fármacos , Estrogênios/agonistas , Hemostáticos/administração & dosagem , Humanos , Mucosite/etiologia , Fitoestrógenos/administração & dosagem , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Receptor PAR-1/fisiologia , Estomatite/tratamento farmacológico , Estomatite/etiologia , Trombofilia/sangue , Trombofilia/etiologia
7.
Cardiovasc Ther ; 2020: 1807941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670409

RESUMO

Nephropathic patients show elevated cardiovascular morbidity and mortality compared to the general population. In order to delve deeper into the understanding of this phenomenon, it is necessary to recognize risk factors that are distinctive to the uremic state, such as oxidative stress and chronic low-grade inflammation. Moreover, gender differences have been reported in nephrology, as it has been observed that chronic kidney disease has higher prevalence in males than in females. The use of an oral food supplement (OFS) containing natural active compounds from Capsicum annuum L., Garcinia cambogia, Centella asiatica L., artichoke, and Aesculus hippocastanum L. which are virtually devoid from side effects, but rich in antioxidant and antiradical properties, could represent a valid therapeutic adjunct in the clinical management of nephropathic patients. Moreover, quantitative analysis performed in vitro on such compounds showed that they expressed good total antioxidant (7.28 gallic acid equivalents) and antiradical activity (above 80%). In this study, 23 male nephropathic patients and 10 age and body composition parameter matched healthy males (control group) were enrolled and took 3 cps/day of OFS for 5 weeks. At the end of the study, the nephropathic patient group showed a statistically significant reduction in the following laboratory parameters: total cholesterol (TC) (p = 0.044), atherogenic index TC/high-density lipoprotein cholesterol (p = 0.010), inflammatory parameters (C-reactive protein, p = 0.048, and erythrocyte sedimentation rate, p = 0.019), systolic (p = 0.044), and diastolic arterial blood pressure (p = 0.003). Regarding body composition, there was an increase in total body water % (p = 0.035) with redistribution of extracellular water % (p = 0.030) and intracellular water % (p = 0.049). In the control group, there was a reduction in fat mass % (p = 0.017) and extracellular water % (p = 0.047). Therefore, this OFS may represent a valid adjunct therapy to counteract comorbidities related to uremia.


Assuntos
Antioxidantes/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Extratos Vegetais/administração & dosagem , Insuficiência Renal Crônica/dietoterapia , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Suplementos Nutricionais/efeitos adversos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
8.
PLoS One ; 15(7): e0236426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716969

RESUMO

BACKGROUND: For stage IV lung cancer patients receiving add-on Viscum album L. (VA) treatment an improved overall survival was detected. Information regarding cost-effectiveness (CE) for comparisons between chemotherapy (CTx) and CTx plus additive VA in stage IV lung cancer treatment is limited. The present study assessed the costs and cost-effectiveness of CTx plus VA (V) compared to CTx alone (C) for stage IV non-small cell lung cancer (NSCLC) patients treatment in a hospital in Germany. METHODS: In the observational real-world data study, data from the Network Oncology clinical registry were utilized. Enrolled stage IV lung cancer patients received the respective therapy (C or V) in a certified German Cancer Center. Cost and cost-effectiveness analyses from the hospital's perspective were investigated on the basis of overall survival (OS) and routine financial controlling data. In addition, the incremental cost-effectiveness ratio (ICER) was calculated. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. RESULTS: 118 patients (C: n = 86, V: n = 32) were included in the analysis, mean age 63.8 years, the proportion of male patients was 55.1%. Adjusted hospital's total mean costs for patients from the C and V group were €16,289, 95%CI: 13,834€-18,744€ (over an adjusted mean OS time of 13.4 months) and €17,992, 95%CI: 13,658-22,326 (over an adjusted mean OS time of 19.1 months), respectively. The costs per additional OS year gained (ICER) with the V-therapy compared to C therapy were €3,586. CONCLUSION: The findings of the present study suggest that the combined use of chemotherapy and VA was clinically effective and comparably cost-effective to chemotherapy alone in our analysed patient sample from the hospital's perspective. Further randomized and prospective cost-effectiveness studies are necessary to complement our findings.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/economia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/economia , Análise Custo-Benefício , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Viscum album/química , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Economia Hospitalar , Feminino , Humanos , Tempo de Internação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Extratos Vegetais/economia , Extratos Vegetais/uso terapêutico , Análise de Sobrevida
9.
Am J Chin Med ; 48(4): 987-1003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431181

RESUMO

Our previous report revealed that Gardenia jasminoides (GJ) has protective effects against acute pancreatitis. So, we examined whether aqueous extract of GJ has anti-inflammation and antifibrotic effects even against cerulein-induced chronic pancreatitis (CP). CP was induced in mice by an intraperitoneal injection of a stable cholecystokinin (CCK) analogue, cerulein, six times a day, four days per week for three weeks. GJ extract (0.1 or 1[Formula: see text]g/kg) or saline (control group) were intraperitoneally injected 1[Formula: see text]h before first cerulein injection. After three weeks of stimulation, the pancreas was harvested for the examination of several fibrotic parameters. In addition, pancreatic stellate cells (PSCs) were isolated using gradient methods to examine the antifibrogenic effects of GJ. In the cerulein-induced CP mice, the histological features of the pancreas showed severe tissue damage such as enlarged interstitial spaces, inflammatory cell infiltrate and glandular atrophy, and tissue fibrosis. However, treatment of GJ reduced the severity of CP such as pancreatic edema and inflammatory cell infiltration. Furthermore, treatment of GJ increased pancreatic acinar cell survival, and reduced pancreatic fibrosis and activation of PSC in vivo and in vitro. In addition, GJ treatment inhibited the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) in the PSCs. These results suggest that GJ attenuated the severity of CP and the pancreatic fibrosis by inhibiting JNK and ERK activation during CP.


Assuntos
Ceruletídeo/efeitos adversos , Gardenia/química , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/prevenção & controle , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fibrose , Injeções Intraperitoneais , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pâncreas/patologia , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Extratos Vegetais/isolamento & purificação
10.
Am J Chin Med ; 48(3): 513-534, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32349519

RESUMO

Ginkgo biloba and its extract have been suggested to have a neuroprotective role in patients with acute ischemic stroke. We aimed to examine the efficacy and safety of Ginkgo biloba use in patients with acute ischemic stroke. We searched seven databases for randomized controlled studies examining the use of Ginkgo biloba in patients with acute ischemic stroke. Relevant studies were retrieved, screened, and data were extracted independently by two reviewers. Random effects meta-analyses were performed to evaluate the efficacy and safety outcomes of Ginkgo biloba. We subsequently assessed the certainty of evidence using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. We found 12 randomized controlled studies enrolling 1466 patients. Pooled results suggest that Ginkgo biloba use was associated with an improvement in neurological function among individuals with AIS with a reduction of 2.87 points on the National Institute of Health Stroke Scale score (95% CI: -4.01--1.74, p<0.001). Ginkgo biloba use was also associated with an improvement in activities of daily living and functional outcome (Mean Difference: 9.52; 4.66-14.33, p<0.001). Subgroup analysis suggest that the impact was larger when using an injectable formulation of Ginkgo biloba compared to the oral formulation. There was no apparent impact of Ginkgo biloba use on all-cause mortality (Risk ratio (RR): 1.21; 0.29-5.09, p=0.80) or cerebrovascular bleeding (RR: 0.82; 0.43-1.57, p=0.55). There was limited evidence on to support the use of gingko biloba in terms of improving quality of life and other stroke events. As such, more studies are needed before it can be recommended for routine use in improving neurological and cognitive function in patients with acute ischemic stroke.


Assuntos
Fitoterapia , Extratos Vegetais/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Atividades Cotidianas , Cognição , Humanos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Qualidade de Vida , Acidente Vascular Cerebral/psicologia , Resultado do Tratamento
11.
J Food Sci ; 85(6): 1956-1962, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32406939

RESUMO

We evaluated the influence of pine bark extract (PBE) on organs, the cytochrome-P450 (CYP) activities in liver and estrogenic effects in normal and ovariectomized (OVX) female mice. The PBE did not affect organ weights and liver-function indexes (activities of alkaline phosphatase, aspartate amino transferase, and alanine amino transferase) at doses; 0.04%, 0.4%, and 2.0% PBE in the diet, in normal and OVX female mice. In the OVX mice, CYP1A1 activity was significantly higher in the 0.4% and 2.0% PBE groups than in the OVX control group, and in the 0.4% and 2.0% PBE groups were significantly higher than in the 0.04% PBE group. CYP1A2 and 3A4 activities were significantly higher in the 2.0% PBE group than in all other groups. The PBE did not affect uterine weight and femoral bone mineral density at all PBE doses. These results showed that the dose of PBE at the recommended human intake, had no toxic and estrogenic effects in normal female and OVX mice, however, it may need attention to use the excess intake of PBE with some drugs in postmenopausal women.


Assuntos
Osteoporose Pós-Menopausa/tratamento farmacológico , Pinus/química , Casca de Planta/química , Extratos Vegetais/administração & dosagem , Animais , Densidade Óssea/efeitos dos fármacos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Feminino , Fêmur/química , Fêmur/crescimento & desenvolvimento , Humanos , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Ovariectomia , Ovário/metabolismo , Ovário/cirurgia , Extratos Vegetais/efeitos adversos
12.
Res Vet Sci ; 131: 186-193, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32388021

RESUMO

Bovine mastitis is the most important disease affecting dairy herds worldwide, causing direct impacts on farms' profitability and food safety issues. The prevention and treatment of this pathology is especially done through antimicrobials, but the increasing antimicrobial resistance of pathogens to this disease may affect the efficiency of conventional drugs. Besides, antimicrobials residues in milk and the environment are a potential threat to human health. Thereby, the use of plant extracts and essential oils may become promising alternatives for the control of bovine mastitis. Antimicrobial properties present in several plants are well described and plant extracts and essential oils are often considered safe to animals, humans and environment. This review summarizes the current problems encountered in the conventional treatment of mastitis, the possibilities of the use of plant extracts and essential oils as alternative agents for the control of these pathogens and the limitations found in the use of these plant derivatives. Finally, the perspectives to the use of plant extracts and essential oils for the treatment of bovine mastitis are presented.


Assuntos
Antibacterianos/uso terapêutico , Mastite Bovina/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Bovinos , Feminino , Óleos Voláteis/administração & dosagem , Extratos Vegetais/administração & dosagem
13.
Cochrane Database Syst Rev ; 5: CD011505, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32421208

RESUMO

BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use. OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification. MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome. AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.


Assuntos
Galactagogos/administração & dosagem , Lactação/efeitos dos fármacos , Leite Humano , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Administração Oral , Peso Corporal/efeitos dos fármacos , Aleitamento Materno , Domperidona/administração & dosagem , Domperidona/efeitos adversos , Feminino , Galactagogos/efeitos adversos , Humanos , Lactente , Recém-Nascido , Metoclopramida/administração & dosagem , Metoclopramida/efeitos adversos , Leite Humano/efeitos dos fármacos , Mães , Fitoterapia/efeitos adversos , Extratos Vegetais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulpirida/administração & dosagem , Sulpirida/efeitos adversos , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/efeitos adversos
14.
Eur. j. anat ; 24(3): 193-203, mayo 2020. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-191468

RESUMO

The degenerative and inflammatory changes were reported in cardiac tissues of rats exposed to zidovudine (ZDV). This study was designed to ex-amine the histochemical changes in the myocardi-um of adult Wistar rats exposed to ZDV and ad-ministered with methanolic extract of Buchholzia coriacea (MEBC) seed. Forty-eight healthy Wistar rats weighing 150-155 g. were randomly assigned into eight groups of six rats each. Group A served as control and received distilled water; group B received 100 mg/kg of ZDV; group C received 600 mg/kg of MEBC; group D received 100 mg/kg of vitamin C; group E received 100 mg/kg of vitamin C and ZDV; group F received 150 mg/kg of MEBC and 100 mg/kg of ZDV; group G received 300 mg/kg of MEBC and 100 mg/kg of ZDV, and group H received 600 mg/kg of MEBC and 100 mg/kg of ZDV. Treatment lasted for a period of 56 days. Blood was collected separately into clean capped plain tubes for biochemical parameters. Heartswere excised, fixed in 10% formal saline and pro-cessed for histology. ZDV induced a significant increase in the serum concentration of Nitric Oxide (NO) and Cardiac Troponin I (cTnI) in the ZDV-alone group when compared to control (p < 0.05). Also, there was reduction in activity of the Glutathi-one reductase (GR) enzyme in the ZDV-alone group relative to control (P = 0.0006, F = 7.0). Distor-tion of the cross banding pattern of cardiac muscle fibres in ZDV-alone group was manifested. These effects were reversed by administration of MEBC compared to vitamin C group


No disponible


Assuntos
Animais , Ratos , Ventrículos do Coração/anatomia & histologia , Metanol/administração & dosagem , Zidovudina/efeitos adversos , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/veterinária , Coração/anatomia & histologia , Capparaceae , Extratos Vegetais/administração & dosagem , Ventrículos do Coração/efeitos dos fármacos , Zidovudina/administração & dosagem , Ratos Wistar/anatomia & histologia , Coração/efeitos dos fármacos , Técnicas Histológicas , Fotomicrografia , Antioxidantes/administração & dosagem , Sementes
15.
Khirurgiia (Mosk) ; (4): 88-94, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32352676

RESUMO

OBJECTIVE: Is to evaluate the advantage of Contractubex gel with regards to influence on vascularisation, pigmentation, thickness, surface size, configuration, and elisticity of postsurgical scars of children (after cheilorinoplasty) in comparison to absence of systematized topical treatment. MATERIAL AND METHODS: Into the prospective, non-interventional, observational, multi-centered, in parallel groups, open, controlled study were included 60 patients aged 2,5 months and older with postsurgical scars after first cheilorinoplasty after 7-14 day after operation. Patients were randomized into 2 groups of 30 patients in each. I group - patients get applications of Contractubex gel 3 times a day (in the morning, in the afternoon, in the evening) in accordance with patient information leaflet. II group - control group with no regular therapy of of postsurgical scars (without treatment or without application of oils and gels with anticsarring action). The period of medicine usage - 9 months and more for each patient, the each patient observation duration is 18 months. RESULTS: After analysis of the primary as well as secondary efficacy criteria (total grade based on POSAS scale, reported by investigator/parent) after 3, 6, 12, 18 months of observation in both groups a positive statistically significant dynamics was registered. At the same time in the Contractubex group results were statistically significantly better than in the control group. Positive dynamics was achieved quickier in the main group than in the contol group and was to observe already after 3 months of therapy, during the whole treatment and observation phase, and after 18 months of therapy. Additionally conducted photodocumentation of postsurgical scar development dynamics in terms of the study confirms positive effect of surgery and absence of visual data regarding keloids or hyperthrophic scars formation in patients in both groups. Adverse events, i. a. pain, itch, burning, long-run hyperemia were not registered during the whole period os study. CONCLUSION: The conducted study has shown high efficacy and safety of Contractubex usage for the treatment of postsurgical scars of children with with congenital cleft lip and palate (from 2,5 months old). The statistically significant advantage of the therapy with Contractubex was demonstrated in comparison with the control group (with no regular topical treatment). The obtained results allow to recommend Contractubex gel as an effective and safe medicine for the treatment of scarring after surgeries for kids directly after sutures removal.


Assuntos
Alantoína/administração & dosagem , Cicatriz/tratamento farmacológico , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Fármacos Dermatológicos/administração & dosagem , Heparina/administração & dosagem , Extratos Vegetais/administração & dosagem , Cicatriz/etiologia , Fenda Labial/complicações , Fissura Palatina/complicações , Combinação de Medicamentos , Géis/administração & dosagem , Humanos , Lactente , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento
16.
Life Sci ; 255: 117721, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32360617

RESUMO

Alcoholic fatty liver disease (AFLD), a major public health problem, has drawn clinical and scientific attention. The study aims to investigate the effect of Ganmeijian [crude extract of malt root, phosphoesterase complex (Pho)] on AFLD, and explore the possible mechanisms. An AFLD rat model was made. 30 and 60 mg/kg Pho were administrated through intestinal fistula for 5 weeks. Compared with those in model group, AST, LDL-C and TC in 30 mg/kg Pho group and TC in 60 mg/kg Pho group decreased. The mRNA level of Fas, Gpat1 and Srebp-1c in Pho groups was significantly reduced. The level of GSH-Px was increased, mitochondrial activity was improved, and the level of MDA and ROS was reduced in Pho groups. Pho shows a beneficial effect on AFLD. The mechanisms are possibly related to Pho inhibiting the expression of fat synthesis genes, protecting the function and increasing the activity of mitochondria in hepatocytes, then reducing the accumulation of ROS and the level of oxidative stress in the liver.


Assuntos
Fígado Gorduroso Alcoólico/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fígado Gorduroso Alcoólico/patologia , Hepatócitos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
17.
PLoS One ; 15(5): e0232482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357366

RESUMO

The study was designed to assess whether plant extracts / phytochemical (D-Pinitol) synergistically combine with antituberculosis drugs and act on Mycobacterium smegmatis (M. smegmatis) as well as assess their mode of action on Mycobacterium tuberculosis (M.tb) Filamenting temperature sensitive mutant Z (FtsZ) protein. Resazurin microtitre plate assay (Checker board) was performed to analyze the activity of plant extracts against M. smegmatis. Synergistic behaviour of plant extracts / D-Pinitol with Isoniazid (INH) and Rifampicin (RIF) were determined by time-kill and checker board assays. Elongation of M. smegmatis cells due to this treatment was determined by light microscopy. The effect of Hexane methanol extract (HXM) plant extracts on cell viability was determined using PI/SYTO9 dual dye reporter Live/Dead assay. Action of HXM plant extracts / D-Pinitol on inhibition of FtsZ protein was done using Guanosine triphosphatase (GTPase) light scattering assay and quantitative Polymerase Chain Reaction (qPCR). The Hexane-methanolic plant extract of Acacia nilotica, Aegle marmelos and Glycyrrhiza glabra showed antimycobacterial activity at 1.56 ± 0.03, 1.32 ± 0.02 and 1.25 ± 0.03 mg/mL respectively and that of INH and RIF were 4.00 ± 0.06 µg/mL and 2.00 ± 0.04 µg/mL respectively. These plant extracts and major phytochemical exudate D-Pinitol was found to act synergistically with antimycobacterial drugs INH and RIF with an FIC index ~ 0.20. Time-Kill kinetics studies indicate that, these plant extracts were bacteriostatic in nature. D-Pinitol in conjunction with INH and RIF exhibited a 2 Log reduction in the growth of viable cells compared to untreated. Attempt to elucidate their mode of action through phenotypic analysis indicated that these plant extracts and D-Pinitol was found to interfere in cell division there by leading to an abnormal elongated cellular morphology. HXM extracts and D-Pinitol synergistically combined with the first line tuberculosis drugs, INH and RIF, to act on M. smegmatis. The increase in the length of M. smegmatis cells on treatment with D-Pinitol and HXM extract of the plants indicated that they hinder the cell division mechanism thereby leading to a filamentous phenotype, and finally leading to cell death. In addition, the integrity of the bacterial cell membrane is also altered causing cell death. Further gene expression analysis showed that these plant extracts and D-Pinitol hampers with function of FtsZ protein which was confirmed through in vitro inhibition of FtsZ-GTPase enzymatic activity.


Assuntos
Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium smegmatis/genética , Plantas Medicinais , Antituberculosos/administração & dosagem , Proteínas de Bactérias/antagonistas & inibidores , Divisão Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/antagonistas & inibidores , Sinergismo Farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Inositol/administração & dosagem , Inositol/análogos & derivados , Isoniazida/administração & dosagem , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium smegmatis/citologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Extratos Vegetais/administração & dosagem , Rifampina/administração & dosagem , Temperatura
18.
Toxicon ; 181: 28-35, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32335100

RESUMO

Gelsemium elegans Benth (G. elegans) is highly toxic to humans and rats, but has insecticides and growth promoting effects on pigs and goats. G. elegans is widely used in livestock, but its in vivo dynamics are entirely unknown. Hence, we investigated the toxicokinetic profiles of G. elegans alkaloids after a single oral dose of G. elegans to pigs (1.0 g/kg) and rats (0.1 g/kg). The results indicated that rats were more susceptible to the toxicity of G. elegans than pigs. The toxicokinetic parameters of 22 and 6 components were obtained in pigs and rats, respectively. The components included 9 and 5 gelsedine-type alkaloids in pigs and rats, respectively. The Tmax results of the 5 gelsedine-type alkaloids indicated that these alkaloids were rapidly absorbed in pigs and rats. The T1/2 values of the 5 gelsedine-type alkaloids indicated that the elimination rates of these alkaloids in pigs were slower than those in rats. In addition, the Cmax and AUC results indicated that the degrees of absorption and exposure of most alkaloids in pigs were higher than those in rats except GS-2. However, the Cmax value of GS-2 (11-methoxy-14-hydroxygelsenicine) in rats was greater than that of pigs, and the Cmax value of 14-hydroxygelsenicine in pigs was merely greater than 3 times that of rats. The present results suggested that the cause of the toxicological differences species of G. elegans might be related to the degrees of absorption and exposure of gelsedine-type alkaloids, especially for the 14-hydroxygelsenicine and GS-2 in different animals.


Assuntos
Gelsemium , Extratos Vegetais/toxicidade , Animais , Humanos , Extratos Vegetais/administração & dosagem , Ratos , Suínos , Toxicocinética
19.
J Cancer Res Clin Oncol ; 146(8): 2089-2097, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32227265

RESUMO

OBJECTIVE: To evaluate the patterns of vitamin and herbal supplement use among patients with advanced gastrointestinal (GI) cancers and the association of such behavior with the efficacy and toxicity of systemic anticancer treatment. METHODS: Project data sphere (PDS) was used to access de-identified datasets of eight clinical trials of advanced GI cancers. Multivariable logistic regression analysis was used to identify factors predicting the use of supplements. Kaplan-Meier survival estimates were used to evaluate the association of supplement use with overall and progression-free survival. Results were stratified according to the site of the primary tumor [pancreatic, gastric, colorectal or hepatocellular carcinoma (HCC)] The association between supplement use and selected chemotherapy side effects was evaluated through Chi-squared testing and subsequent logistic regression. RESULTS: A total of 3441 patients were included in the analysis. Of these, 775 patients reported use of supplements and 2666 patients reported no use of supplements. Higher ECOG performance score (Odds ratio: OR for ECOG 1 versus 0: 1.629; 95% CI 1.363-1.947; P < 0.001) and pancreatic primary site (OR for gastric cancer versus pancreatic cancer: 0.538; 95% CI 0.408-0.709; P < 0.001) was associated with greater use of these supplements. Supplement use was associated with a better overall survival among patients with pancreatic cancer (P = 0.002) but not other GI malignancies. Supplement use was associated with a higher probability of anemia and diarrhea among patients with pancreatic cancer (P < 0.001 for both), gastric cancer (P = 0.016; P = 0.036, respectively) and colorectal cancer (P < 0.001 for both). CONCLUSIONS: There is an association between the use of vitamin and herbal supplements and a higher probability of hematologic and gastrointestinal toxicities. There is a need for more studies to confirm the association between such behavior and better overall survival among patients with pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gastrointestinais/dietoterapia , Neoplasias Gastrointestinais/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Vitaminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Vitaminas/efeitos adversos
20.
Poult Sci ; 99(4): 1875-1887, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241467

RESUMO

The present study was undertaken to investigate the effect of aqueous Withania somnifera root (WSR) extract in broiler chicks experimentally infected with Escherichia coli O78 @ 107 CFU/0.5 ml intraperitoneally. Clinical signs and mortality due to colibacillosis observed in infected chicks were mild and lasted for short duration in WSR extract supplemented group as compared with the nonsupplemented group. A significant increase in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, and creatine phosphokinase activities and a decrease in total protein and albumin concentrations were observed in the infected groups, though these changes were of lower magnitude in WSR extract supplemented group. A significantly higher activity of oxidative blood parameters such as superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase enzymes were noticed in WSR extract supplemented group. The WSR extract supplemented group revealed significantly higher E. coli-specific antibody titer and enhanced lymphocyte proliferation response as compared with the nonsupplemented group. The gross and histopathological lesions of colibacillosis were mild in the WSR extract-supplemented infected group as compared with the nonsupplemented infected group. Withania somnifera root extract supplementation produced 31.48 and 34.38% protection in the gross and histopathological lesions in E. coli infected chicks, respectively. It is concluded that supplementation of 20% WSR extract @ 20 ml/L of water caused a reduction in the severity, mortality, and recovery period of E. coli infection and enhanced the humoral and cellular immune responses suggesting its protective effect on limiting the pathology of E. coli infection in broiler chickens.


Assuntos
Anti-Infecciosos/metabolismo , Galinhas , Infecções por Escherichia coli/veterinária , Escherichia coli/fisiologia , Extratos Vegetais/metabolismo , Doenças das Aves Domésticas/tratamento farmacológico , Withania/química , Ração Animal/análise , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Raízes de Plantas/química , Doenças das Aves Domésticas/microbiologia , Distribuição Aleatória
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