Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.130
Filtrar
1.
Am J Otolaryngol ; 41(4): 102498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354483

RESUMO

PURPOSE: Osmotic diuretics such as glycerol are used for diagnostic purposes in patients with a suspect of Meniere's disease (MD). Scientific evidence in the animal model and in humans has shown that glycerol can induce a reduction in endolymphatic hydrops; however, its use for therapeutic purposes in MD has never been reported. The aim of this study was to evaluate the effectiveness on symptom control of intravenous glycerol in a sample of patients with definite unilateral MD not responsive to dietary restrictions. MATERIALS AND METHODS: Forty patients with unilateral intractable MD were included in the study. After audio-vestibular evaluation, patients were treated with intravenous 10% glycerol with 0.9% sodium chloride, 0.5 g/kg ml once a day for 2 consecutive days every fifteen days for six months. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Tinnitus and quality of life were evaluated through the Tinnitus Handicap Inventory and the Functionality Level Scale questionnaires. RESULTS: Before treatment, patients had an average of 3.2 vertigo attacks/month; during the six months after treatment the average number of attacks/month decreased to 1.2 (p < 0.0001). At the end of the study period, 25 patients (62.5%) were in Class B vertigo control; 10 patients (25%) in Class C; and 5 patients (12.5%) in Class D. No patients were in Class A, E and F. No hearing deterioration was found in all treated patients. Quality of life according to administered questionnaires improved after treatment. CONCLUSIONS: In our sample, intravenous infusion of glycerol for two consecutive days every fifteen days for six months based on the patient's weight improved vertigo attacks and reduced the discomfort generated by tinnitus raising quality of life in patients with unilateral MD unresponsive to dietary restrictions.


Assuntos
Glicerol/administração & dosagem , Doença de Meniere/tratamento farmacológico , Diuréticos Osmóticos , Esquema de Medicação , Humanos , Infusões Intravenosas , Doença de Meniere/diagnóstico , Resultado do Tratamento
2.
Arch Anim Nutr ; 74(4): 325-342, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32362138

RESUMO

The objective of this study was to evaluate the effects of in ovo injection with glycerol (GLY) and insulin-like growth factor (IGF-I) on hatchability, biochemical parameters, intestinal morphometry, performance, and carcass characteristics of broiler chickens. A total of 400 fertilised eggs were distributed into five experimental groups. The treatments were arranged as non-injected (control), saline solution injected (0.9% NaCl solution), GLY solution injected (10 nmol/ml), IGF-I solution injected (100 ng/ml), and GLY + IGF-I solution injected. At 17.5 d of incubation, 0.5 ml of each solution was injected into the amniotic fluid of each egg of the injected groups. The injection of different solutions did not influence the hatchability and incubation time of the eggs. Compared to intact eggs, IGF-I and IGF-I+ GLY increased (p < 0.01) the blood IGF-I at hatching. Higher hepatic glycogen was observed (p < 0.05) with GLY or IGF-I. The tested substances decreased (p = 0.02) the fructose 1,6-biphosfate phosphatase activity but did not affect glycaemia. No difference in performance was observed in the first week. Higher feed intake and weight gain with lower feed conversion ratio was obtained ( p  < 0.05) with IGF-I at 14 d. At 21 d, higher weight gain was obtained (p = 0.05) with IGF-I, GLY, IGF-I, and GLY + IGF-I, resulting (p < 0.01) in birds with greater weight gain at 35 and 42 d of age. GLY provided higher villus height in the ileum at hatching and at 7 d of age. The tested solutions increased the relative weight of the liver at hatching. At 42 d of age, no carcass characteristics were influenced. It is concluded that GLY and IGF-I, together or separately, can be used in the in ovo feeding to improve the post-hatch performance of broilers, without affecting hatchability and carcass composition.


Assuntos
Galinhas/fisiologia , Glicerol/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Intestinos/efeitos dos fármacos , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Galinhas/anatomia & histologia , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Glicerol/administração & dosagem , Injeções/veterinária , Fator de Crescimento Insulin-Like I/administração & dosagem , Intestinos/anatomia & histologia , Óvulo/efeitos dos fármacos
3.
Intern Med ; 59(13): 1659-1663, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32269190

RESUMO

A 66-year-old man with type 2 diabetes was admitted for glycemic control and weight loss. The rectal mucosa was unfortunately injured during glycerin enema administration in preparation for colonoscopy, after which dark red urine and renal dysfunction were observed. Considering the clinical diagnosis of glycerol-induced hemolysis and acute kidney injury, intravenous hydration and haptoglobin administration were started, which successfully treated the dark red urine and renal dysfunction. This case highlights the importance of appropriate glycerin enema administration and emphasizes the need to recognize glycerol-induced hemolysis and acute kidney injury as complications of glycerin enemas. This case also provides insight into glycerol-induced hemolysis and acute kidney injury as complications of glycerin enemas.


Assuntos
Lesão Renal Aguda/etiologia , Diabetes Mellitus Tipo 2/complicações , Enema/efeitos adversos , Hemólise , Reto/lesões , Idoso , Colonoscopia , Glicerol/administração & dosagem , Testes Hematológicos , Humanos , Masculino , Reto/patologia
4.
Cochrane Database Syst Rev ; 3: CD000475, 2020 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-32199406

RESUMO

BACKGROUND: Pelvic adhesions can form secondary to inflammation, endometriosis, or surgical trauma. Strategies to reduce pelvic adhesion formation include placing barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene, and fibrin or collagen sheets between pelvic structures. OBJECTIVES: To evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth, and postoperative adhesions in women of reproductive age. SEARCH METHODS: We searched the following databases in August 2019: the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries. We searched reference lists of relevant papers, conference proceedings, and grey literature sources. We contacted pharmaceutical companies for information and handsearched relevant journals and conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) on the use of barrier agents compared with other barrier agents, placebo, or no treatment for prevention of adhesions in women undergoing gynaecological surgery. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for eligibility and risk of bias and extracted data. We calculated odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) using a fixed-effect model. We assessed the overall quality of the evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods. MAIN RESULTS: We included 19 RCTs (1316 women). Seven RCTs randomised women; the remainder randomised pelvic organs. Laparoscopy (eight RCTs) and laparotomy (11 RCTs) were the primary surgical techniques. Indications for surgery included myomectomy (seven RCTs), ovarian surgery (five RCTs), pelvic adhesions (five RCTs), endometriosis (one RCT), and mixed gynaecological surgery (one RCT). The sole indication for surgery in three of the RCTs was infertility. Thirteen RCTs reported commercial funding; the rest did not state their source of funding. No studies reported our primary outcomes of pelvic pain and live birth rate. Oxidised regenerated cellulose versus no treatment at laparoscopy or laparotomy (13 RCTs) At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose at laparoscopy reduced the incidence of de novo adhesions (OR 0.50, 95% CI 0.30 to 0.83, 3 RCTs, 360 participants; I² = 75%; very low-quality evidence) or of re-formed adhesions (OR 0.17, 95% CI 0.07 to 0.41, 3 RCTs, 100 participants; I² = 36%; very low-quality evidence). At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose affected the incidence of de novo adhesions after laparotomy (OR 0.72, 95% CI 0.42 to 1.25, 1 RCT, 271 participants; very low-quality evidence). However, the incidence of re-formed adhesions may have been reduced in the intervention group (OR 0.38, 95% CI 0.27 to 0.55, 6 RCTs, 554 participants; I² = 41%; low-quality evidence). No studies reported results on pelvic pain, live birth rate, adhesion score, or clinical pregnancy rate. Expanded polytetrafluoroethylene versus oxidised regenerated cellulose at gynaecological surgery (two RCTs) We are uncertain whether expanded polytetrafluoroethylene reduced the incidence of de novo adhesions at second-look laparoscopy (OR 0.93, 95% CI 0.26 to 3.41, 38 participants; very low-quality evidence). We are also uncertain whether expanded polytetrafluoroethylene resulted in a lower adhesion score (out of 11) (MD -3.79, 95% CI -5.12 to -2.46, 62 participants; very low-quality evidence) or a lower risk of re-formed adhesions (OR 0.13, 95% CI 0.02 to 0.80, 23 participants; very low-quality evidence) when compared with oxidised regenerated cellulose. No studies reported results regarding pelvic pain, live birth rate, or clinical pregnancy rate. Collagen membrane with polyethylene glycol and glycerol versus no treatment at gynaecological surgery (one RCT) Evidence suggests that collagen membrane with polyethylene glycol and glycerol may reduce the incidence of adhesions at second-look laparoscopy (OR 0.04, 95% CI 0.00 to 0.77, 47 participants; low-quality evidence). We are uncertain whether collagen membrane with polyethylene glycol and glycerol improved clinical pregnancy rate (OR 5.69, 95% CI 1.38 to 23.48, 39 participants; very low-quality evidence). One study reported adhesion scores but reported them as median scores rather than mean scores (median score 0.8 in the treatment group vs median score 1.2 in the control group) and therefore could not be included in the meta-analysis. The reported P value was 0.230, and no evidence suggests a difference between treatment and control groups. No studies reported results regarding pelvic pain or live birth rate. In total, 15 of the 19 RCTs included in this review reported adverse events. No events directly attributed to adhesion agents were reported. AUTHORS' CONCLUSIONS: We found no evidence on the effects of barrier agents used during pelvic surgery on pelvic pain or live birth rate in women of reproductive age because no trial reported these outcomes. It is difficult to draw credible conclusions due to lack of evidence and the low quality of included studies. Given this caveat, low-quality evidence suggests that collagen membrane with polyethylene glycol plus glycerol may be more effective than no treatment in reducing the incidence of adhesion formation following pelvic surgery. Low-quality evidence also shows that oxidised regenerated cellulose may reduce the incidence of re-formation of adhesions when compared with no treatment at laparotomy. It is not possible to draw conclusions on the relative effectiveness of these interventions due to lack of evidence. No adverse events directly attributed to the adhesion agents were reported. The quality of the evidence ranged from very low to moderate. Common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out.


Assuntos
Celulose Oxidada/uso terapêutico , Infertilidade Feminina/cirurgia , Politetrafluoretileno/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Colo do Útero/cirurgia , Colágeno/administração & dosagem , Feminino , Fibrina/administração & dosagem , Glicerol/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Incidência , Laparoscopia/efeitos adversos , Laparotomia/efeitos adversos , Membranas Artificiais , Dor Pós-Operatória/prevenção & controle , Pelve/cirurgia , Polietilenoglicóis/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Cirurgia de Second-Look , Aderências Teciduais/epidemiologia , Aderências Teciduais/prevenção & controle , Viscossuplementos/administração & dosagem
5.
Arq. bras. med. vet. zootec. (Online) ; 72(1): 243-252, Jan.-Feb. 2020. tab
Artigo em Português | LILACS, VETINDEX | ID: biblio-1088938

RESUMO

O objetivo deste estudo foi avaliar o perfil de ácidos graxos (AG) do leite de vacas alimentadas com dietas à base de silagem de milho contendo 0% e 8,9% de glicerina bruta (GB) na matéria seca (MS). Foram utilizadas 18 vacas Holandês x Gir com 48±18 dias em lactação, produzindo 19,8±4,9kg/dia de leite. Utilizou-se delineamento de blocos ao acaso, com nove vacas/tratamento e duas medidas repetidas no tempo, com os resultados analisados por modelos mistos. A inclusão de GB na dieta não alterou a ingestão de MS, mas reduziu os consumos dos AG oleico, linoleico e α-linolênico. Os teores dos AG mirístico, palmítico, rumênico, vacênico, esteárico, oleico, linoleico, α-linolênico e CLA trans-10 cis-12 na gordura do leite foram semelhantes entre dietas. A inclusão de GB reduziu os teores dos AG elaídico e C18:1 trans-10 e aumentou os teores dos AG de cadeia ímpar linear e do ácido láurico. Não houve efeito da inclusão da GB sobre os índices de aterogenicidade e trombogenicidade da gordura do leite. Concluiu-se que a inclusão de glicerina bruta em dieta à base de silagem de milho não afetou a qualidade nutricional da gordura do leite de vacas Holandês x Gir.(AU)


The objective of this study was to evaluate the milk fatty acid (FA) composition of cows fed corn silage-based diets containing 0% and 8.9% of crude glycerin (GB) on a dry matter (DM) basis. Eighteen Holstein x Gyr cows with 48±18 days in milk and producing 19.8±4.9kg milk/day were used in the study. The experimental design was a randomized block with nine cows per treatment and two repeated measures. Results were analyzed using mixed models. The milk fat contents of myristic, palmitic, rumenic, vaccenic, estearic, oleic, linoleic, α-linolenic, and trans-10 cis-12 CLA were similar between diets. Dietary inclusion of GB decreased elaidic and trans-10 C18:1, and increased lauric acid and odd linear-chain FA contents in milk fat. Both atherogenicity and trombogenicity indices were unaffected by GB inclusion. It was concluded that GB inclusion in corn silage-based diets had no effect on the nutritional quality of milk fat from Holstein x Gyr dairy cows.(AU)


Assuntos
Animais , Feminino , Bovinos , Silagem , Leite/química , Ácidos Graxos/análise , Glicerol/administração & dosagem , Biocombustíveis , Ração Animal
6.
Trop Anim Health Prod ; 52(2): 565-571, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31463661

RESUMO

The aim of this trial was to determine the effect of ruminal fluid adapted to crude glycerol supplementation on in vitro methane and fermentation parameters of the forage Pennisetum clandestinum Hochst. Ex Chiov (Kikuyu forage) of 35 (D35) and 45 days (D45) of regrowth. Four non-lactating cannulated Holstein cows with 600 ± 33 kg LW, under a randomized Latin square design (4 animals × 4 periods), were used to obtain ruminal fluid after adaptation for 13 days within each period to supplementation in the rumen with crude glycerol (GL): 0 (GL0), 500 (GL1), 1000 (GL2), and 1500 g/cow/day (GL3). All the variables were analyzed under a 4 × 2 split-plot arrangement, where the ruminal fluid adaptation to supplementation with GL and its interaction with the incubated diets (GL× D) were analyzed. Ruminal pH values and in vitro apparent degradability of the dry matter (DMd) and organic matter (OMd) were not affected, with a decrease in the concentrations of NH3-N and acetate by the ruminal fluid adapted to crude glycerol. The concentrations of propionate and butyrate increased, without affecting the total concentration of VFA in the ruminal fluid. The in vitro methane production increased with forage D35 and GL1, GL2, GL3. The in vitro methane production with the D45 forage increased with the ruminal fluid adapted to GL2 and GL3. The ruminal fluid adapted to crude glycerol supplementation increased in vitro methane production when incubating the forage Kikuyu.


Assuntos
Bovinos/metabolismo , Glicerol/metabolismo , Metano/metabolismo , Pennisetum , Rúmen/metabolismo , Ração Animal/análise , Animais , Líquidos Corporais , Feminino , Fermentação , Glicerol/administração & dosagem , Pennisetum/metabolismo , Distribuição Aleatória
7.
Eur Arch Otorhinolaryngol ; 277(1): 77-83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605188

RESUMO

PURPOSE: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere's disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone. METHODS: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered. RESULTS: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group. CONCLUSION: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.


Assuntos
Grão Comestível/metabolismo , Doença de Meniere/metabolismo , Neuropeptídeos/metabolismo , Fármacos do Sistema Nervoso Periférico/metabolismo , Vertigem/metabolismo , Adulto , Idoso , Dexametasona/administração & dosagem , Feminino , Glicerol/administração & dosagem , Humanos , Masculino , Doença de Meniere/diagnóstico , Doença de Meniere/tratamento farmacológico , Pessoa de Meia-Idade , Fármacos do Sistema Nervoso Periférico/administração & dosagem , Qualidade de Vida , Inquéritos e Questionários , Zumbido/diagnóstico , Zumbido/tratamento farmacológico , Vertigem/tratamento farmacológico , Vertigem/etiologia
8.
Trop Anim Health Prod ; 52(2): 871-879, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31641927

RESUMO

The increase in haylage production leads to the search for additives that improve its fermentation and nutritional value. This study aimed to assess the effect of adding crude glycerine and microbial additives on losses, fermentation parameters and nutritional value of haylage. The treatments were composed of three doses of crude glycerine (0, 60 and 120 g/kg forage) and three types of inoculation (control (distilled water), SIL (Lactobacillus plantarum 2.6 × 1010 CFU/g and Pediococcus pentosaceus 2.6 × 1010 CFU/g) and INC (Bacillus subtilis 2.0 × 109 CFU/g, Lactobacillus plantarum 8.0 × 109 CFU/g and Pediococcus acidilactici 1.0 × 1010 CFU/g)). A negative linear effect was observed in the fibre fraction contents of the haylages as a function of crude glycerine addition, which contributed to similarly increasing dry matter in vitro digestibility coefficients. The use of inoculants also resulted in haylages with higher digestibility coefficients of 635.1 and 646.8 g/kg dry matter (DM) in the treatments inoculated with INC and SIL, respectively. Fermentation losses were reduced by adding crude glycerine and were not impacted by the microbial inoculants. Higher lactic acid productions were obtained as a function of crude glycerine doses. Acetic acid productions decreased from 29.3 g/kg DM to 19.2 g/kg DM between crude glycerine doses of 0 and 120 g/kg forage, respectively. SIL led to the highest lactic acid productions compared to INC and the control. Crude glycerine improves the fermentation parameters and nutritional value of haylages. However, the microbial inoculants had little impact on the parameters assessed.


Assuntos
Inoculantes Agrícolas/metabolismo , Fermentação , Glicerol/metabolismo , Silagem/análise , Bacillus subtilis/metabolismo , Glicerol/administração & dosagem , Lactobacillus plantarum/metabolismo , Valor Nutritivo , Pediococcus/metabolismo
9.
Toxicol Appl Pharmacol ; 386: 114833, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756429

RESUMO

One of the main problems for the development of pulmonary formulations is the low availability of approved excipients. Polyglycerol esters of fatty acids (PGFA) are promising molecules for acting as excipient for formulation development and drug delivery to the lung. However, their biocompatibility in the deep lung has not been studied so far. Main exposed cells include alveolar epithelial cells and alveolar macrophages. Due to the poor water-solubility of PGFAs, the exposure of alveolar macrophages is expected to be much higher than that of epithelial cells. In this study, two PGFAs and their mixture were tested regarding cytotoxicity to epithelial cells and cytotoxicity and functional impairment of macrophages. Cytotoxicity was assessed by dehydrogenase activity and lactate dehydrogenase release. Lysosome function, phospholipid accumulation, phagocytosis, nitric oxide production, and cytokine release were used to evaluate macrophage function. Cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/ml accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs in concentrations up to 1 mg/ml can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.


Assuntos
Excipientes/farmacologia , Excipientes/toxicidade , Ácidos Graxos/toxicidade , Glicerol/toxicidade , Polímeros/toxicidade , Células A549 , Administração por Inalação , Proteínas Aviárias/metabolismo , Citocinas/metabolismo , Excipientes/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Glicerol/administração & dosagem , Glicerol/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Polímeros/administração & dosagem , Polímeros/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Testes de Toxicidade
10.
Gynecol Oncol ; 156(2): 293-300, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31826802

RESUMO

OBJECTIVE: Paclitaxel micellar was developed to avoid Cremophor-EL (Cr-EL) associated dose limiting toxicity and to allow a shorter infusion time. The efficacy and safety of paclitaxel micellar (+carboplatin) was compared to Cr-EL paclitaxel (+carboplatin) in recurrent platinum-sensitive ovarian, fallopian tube or peritoneal carcinoma. METHODS: This was a multicentre, open-label, randomized phase III trial. Adult patients with recurrent disease was assigned to six 3-week cycles of paclitaxel micellar (250 mg/m2) administered as 1-h infusion or Cr-EL paclitaxel (175 mg/m2) as 3-h infusion. Both arms received carboplatin (AUC 5-6). Primary objective was non-inferiority for progression free survival (PFS) using computed tomography scans. Overall survival (OS) was included as secondary endpoint. RESULTS: Between 2009 and 2013, 789 patients were randomized to receive experimental (N = 397) or control (N = 392) treatment. PFS for paclitaxel micellar was non-inferior to Cr-EL paclitaxel with a hazard ratio of 0.86 (95% CI: 0.72;1.03) in the per protocol population (PP), favouring paclitaxel micellar (non-inferiority margin was 1.2). Non-inferiority of OS was shown in the PP population with a hazard ratio of 0.95 (95% CI: 0.78; 1.16), favouring paclitaxel micellar (non-inferiority margin was 1.185). The most common adverse event was neutropenia (grade ≥ 3); 245 patients (79%) for paclitaxel micellar vs 213 patients (66%) for Cr-EL paclitaxel. The frequency of peripheral sensory neuropathy (any grade) was similar between the arms; 16% for paclitaxel micellar and 20% for Cr-EL paclitaxel. CONCLUSION: Paclitaxel micellar (+ carboplatin) is non-inferior to Cr-EL paclitaxel (+ carboplatin) in terms of PFS and OS in the studied population. It provides a treatment option of a higher paclitaxel dose with a shorter infusion time without mandatory premedication. TRIAL REGISTRATION NUMBER: 2008-002668-32 (EudraCT), NCT00989131 (ClinicalTrials.gov).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/patologia , Feminino , Glicerol/administração & dosagem , Glicerol/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Micelas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Intervalo Livre de Progressão , Qualidade de Vida , Taxa de Sobrevida
11.
J Vet Med Sci ; 82(2): 168-171, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31875598

RESUMO

Recently, we have shown that glycerol induces early fibrosis in rat muscles which persists up to two weeks after injury. The current study aims to determine the possible factor associated with fibrosis of rat muscle following glycerol injury. Eight-week-old male Wistar rats received either glycerol only (as a control) or a co-treatment of neutralizing antibody to transforming growth factor (TGF)-ß1 (5 and 12.5 µg). Both antibody doses significantly decreased fibrosis and improved muscle regeneration suggesting that anti-TGF-ß1 antibody has both anti-fibrotic and myogenic effects. In conclusion, fibrosis developed in glycerol-injured rat muscles, might be mediated, in part, by the upregulation of TGF-ß1 expression. Targeting TGF-ß1 could be a promising approach for inhibiting fibrosis and enhancing muscle regeneration.


Assuntos
Glicerol/toxicidade , Músculo Esquelético/efeitos dos fármacos , Doenças Musculares/induzido quimicamente , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Animais , Anticorpos Neutralizantes , Modelos Animais de Doenças , Fibrose/induzido quimicamente , Glicerol/administração & dosagem , Injeções Intramusculares , Masculino , Músculo Esquelético/patologia , Doenças Musculares/patologia , Ratos Wistar , Regeneração/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo
12.
Curr Med Sci ; 39(6): 1003-1008, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845234

RESUMO

Human beings are increasingly exposed to phthalates, which are a group of chemicals used to make plastics more flexible and harder to break, and simultaneously ingesting abundant food emulsifiers via daily diet. The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate (GMS) on male reproductive toxicity caused by di(2-ethylhexyl) phthalate (DEHP, one of the phthalates) and explore the underlying mechanism. Thirty male Sprague-Dawley rats were randomly divided into control group, DEHP group and DEHP+GMS group. Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS. After 30 days of continuous intervention, it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group (P<0.01). The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group (P<0.05). More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group. The expression levels of cell cycle checkpoint kinase 1 (Chk1), cell division cycle gene 2 (Cdc2), and cyclin-dependent kinase 2 (CDK2) were down-regulated in DEHP group, and this tendency was more significant in DEHP+GMS group (P<0.05 or P<0.01). There was no significant difference in the P-glycoprotein (P-gp) expression between DEHP group and control group. However, P-gp was markedly down-regulated in DEHP+GMS group (P<0.01). The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.


Assuntos
Dietilexilftalato/toxicidade , Emulsificantes/toxicidade , Glicerol/toxicidade , Reprodução/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Animais , Proteína Quinase CDC2/metabolismo , Quinase 1 do Ponto de Checagem/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Dietilexilftalato/administração & dosagem , Regulação para Baixo , Emulsificantes/administração & dosagem , Glicerol/administração & dosagem , Masculino , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testículo/efeitos dos fármacos , Testosterona/sangue
13.
Actual. osteol ; 15(3): 180-191, Sept-Dic. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1104226

RESUMO

Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappa b receptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG). The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids. Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzymelinked immunoassay was used to measure intercellular mediator levels in the serum. The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals' blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group. In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future. (AU)


Las enfermedades metabólicas óseas se caracterizan por un desequilibrio en el proceso de remodelación ósea en los que participan mediadores tales como receptor del activador del factor nuclear- kappa- b (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, recuentemente empleados en el tratamiento de la enfermedad renal crónica, exacerban este desequilibrio. En la enfermedad esclerótica renal, las moléculas de adhesión celular P-selectina and galectina-3 tienen un rol fundamental. El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelación ósea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crónica con tratamiento glucocorticoideo. Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crónica con afección de la remodelación ósea (ERC); animales con afección de la remodelación ósea expuestos a glucocorticoides (GC); enfermedad renal crónica con afección de la remodelación ósea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioquímicamente, histológicamente y por medición de la densidad ósea. RANKL, OPG, Pselectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno análisis. En los 3 grupos experimentales la densidad ósea se evidenció reducida y los niveles séricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmática en GC y ERC+GC se encontró reducida y aumentada en los animales ERC, en comparación con los animales controles. La concentración sérica de P-selectina sérica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmáticos de los animales intactos. El avance del conocimiento sobre la regulación de la remodelación ósea a través de la interacción de mediadores sistémicos, en un futuro, puede conducir al desarrollo de nuevas estrategias terapéuticas para la prevención de la osteoporosis en pacientes con enfermedad renal crónica. (AU)


Assuntos
Animais , Ratos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/induzido quimicamente , Remodelação Óssea/efeitos dos fármacos , Nefropatias/fisiopatologia , Osteoporose/prevenção & controle , Doenças Ósseas Metabólicas/diagnóstico , Dexametasona/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Clorofórmio/uso terapêutico , Ratos Wistar , Selectina-P/efeitos dos fármacos , Selectina-P/sangue , Galectina 3/efeitos dos fármacos , Galectina 3/sangue , Ligante RANK/efeitos dos fármacos , Ligante RANK/sangue , Osteoprotegerina/efeitos dos fármacos , Osteoprotegerina/sangue , Glucocorticoides/efeitos adversos , Glicerol/administração & dosagem , Nefropatias/tratamento farmacológico
14.
BMC Anesthesiol ; 19(1): 169, 2019 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-31470796

RESUMO

BACKGROUND: We previously demonstrated that lubrication of an endotracheal tube (ETT) cuff with K-Y™ jelly strongly and significantly inhibited the increase in cuff pressure during nitrous oxide (N2O) exposure in vitro. However, in our previous study, we identified critical differences between some influential factors, such as the amount of lubricant retained on the cuff, and studied temperature differences between laboratory and clinical conditions. Therefore, it remained unclear whether this effect holds true in clinical settings. METHODS: We first sought to study how changes in the amount of K-Y™ jelly and temperature influence the inhibitory effects of the lubricant on the increase in N2O-induced cuff pressure in vitro. Furthermore, we aimed to determine whether the application of K-Y™ jelly inhibits the increase in ETT cuff pressure during general anesthesia using N2O in adult patients. RESULTS: In the laboratory studies, we found that K-Y™ jelly inhibited the cuff pressure increase dose-dependently when the dose of K-Y™ jelly was varied (P = 0.02), and that such an inhibitory effect decreased with an increase in the studied temperature (P = 0.019). In the clinical study, lubrication with K-Y™ jelly slightly, but significantly, delayed the increase in ETT cuff pressure during general anesthesia with N2O (P = 0.029). However, the inhibitory effect in the clinical settings was smaller than that in vitro. CONCLUSIONS: Lubrication of the ETT cuff with K-Y™ jelly may delay the increase in cuff pressure during general anaesthesia with N2O. However, the clinical significance of this effect may be limited. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000031377 on March 1, 2019.


Assuntos
Celulose/análogos & derivados , Glicerol/farmacologia , Intubação Intratraqueal/métodos , Lubrificação , Óxido Nitroso/administração & dosagem , Fosfatos/farmacologia , Pressão , Propilenoglicóis/farmacologia , Equipamentos Cirúrgicos , Celulose/administração & dosagem , Celulose/farmacologia , Relação Dose-Resposta a Droga , Feminino , Glicerol/administração & dosagem , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Fosfatos/administração & dosagem , Propilenoglicóis/administração & dosagem , Temperatura , Fatores de Tempo
15.
J Control Release ; 308: 190-196, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31319095

RESUMO

The penetration of small molecules through the human skin is a major issue for both safety and efficacy issues in cosmetics and pharmaceutic domains. To date, the quantification of active molecular compounds in human skin following a topical application uses ex vivo skin samples mounted on Franz cell diffusion set-up together with appropriate analytical methods. Coherent anti-Stokes Raman scattering (CARS) has also been used to perform active molecule quantification on ex vivo skin samples, but no quantification has been described in human skin in vivo. Here we introduce and validate a framework for imaging and quantifying the active molecule penetration into human skin in vivo. Our approach combines nonlinear imaging microscopy modalities, such as two-photon excited auto-fluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS), together with the use of deuterated active molecules. The imaging framework was exemplified on topically applied glycerol diluted in various vehicles such as water and xanthan gel. In vivo glycerol quantitative percutaneous penetration over time was demonstrated, showing that, contrary to water, the xanthan gel vehicle acts as a film reservoir that releases glycerol continuously over time. More generally, the proposed imaging framework provides an enabling platform for establishing functional activity of topically applied products in vivo.


Assuntos
Glicerol/farmacocinética , Absorção Cutânea , Pele/metabolismo , Análise Espectral Raman , Administração Cutânea , Glicerol/administração & dosagem , Humanos , Microscopia de Fluorescência , Fótons , Polissacarídeos Bacterianos/química , Água/química
16.
Drug Deliv ; 26(1): 680-688, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31274009

RESUMO

Neuroprotection has proven clinically unsuccessful in subarachnoid hemorrhage. We believe that this is because the major component in the early damage pathway, the vascular wall, has not been given the necessary focus. U0126 is a potent inhibitor of vascular phenotypical changes, exemplified by functional endothelin B (ETB) receptor upregulation. The current study aimed to determine the optimal dose of U0126 ex vivo and test the toxicology of this dose in vivo. To find the optimal dose and test a suitable in vivo delivery system, we applied an ex vivo model of blood flow cessation and investigated functional ETB receptor upregulation (using a specific agonist) as the primary endpoint. The secondary endpoint was depolarization-induced contractility assessed by 60 mM K+ stimuli. Furthermore, an in vivo toxicology study was performed on the optimal selected doses. U0126 (10 µM) had a strong effect on the prevention of functional ETB receptor contractility, combined with minimal effect on the depolarization-induced contractility. When cremophor EL was chosen for drug delivery, it had an inhibitory and additive effect (combined with U0126) on the ETB receptor contractility. Hence, 10 µM U0126 in 0.5% cremophor EL seems to be a dose that will be close to the maximal inhibition observed ex vivo on basilar arteries, without exhibiting side effects in the toxicology studies. U0126 and cremophor EL are well tolerated at doses that have effect on ETB receptor upregulation. Cremophor EL has an additional positive effect, preventing functional ETB receptor upregulation, making it suitable as a drug delivery system.


Assuntos
Butadienos/administração & dosagem , Glicerol/análogos & derivados , Nitrilos/administração & dosagem , Receptor de Endotelina B/metabolismo , Animais , Butadienos/líquido cefalorraquidiano , Butadienos/farmacologia , Butadienos/toxicidade , Portadores de Fármacos , Sinergismo Farmacológico , Feminino , Glicerol/administração & dosagem , Glicerol/farmacologia , Glicerol/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Modelos Biológicos , Nitrilos/líquido cefalorraquidiano , Nitrilos/farmacologia , Nitrilos/toxicidade , Ratos , Ratos Sprague-Dawley , Receptor de Endotelina B/agonistas , Regulação para Cima
17.
Sci Rep ; 9(1): 10221, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308389

RESUMO

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172-0.5 µm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles <0.3 µm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system.


Assuntos
Aerossóis/administração & dosagem , Aerossóis/química , Nicotina/administração & dosagem , Aerossóis/análise , Sistemas de Liberação de Medicamentos/métodos , Sistemas Eletrônicos de Liberação de Nicotina , Glicerol/administração & dosagem , Humanos , Nicotina/farmacocinética , Tamanho da Partícula , Propilenoglicol , Fumantes
18.
J Anim Physiol Anim Nutr (Berl) ; 103(4): 988-996, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31172562

RESUMO

The effects of adding crude glycerine with sodium monensin or essential oils to beef cattle diets on the intake, degradability of DM and nutrients, rumen concentration of volatile fatty acids (VFA) and in vitro gas production were evaluated. Five ruminally cannulated Nellore steers were randomly assigned to a 5 × 5 Latin square design. The treatments were as follows: CONT, without crude glycerine and additives; EO, with essential oils and without crude glycerine; MON, with sodium monensin and without crude glycerine; EOG, with essential oils and crude glycerine; MONG, with sodium monensin and crude glycerine. Treatments with essential oil and sodium monensin increased the NDF and STC intake and the DM degradability. When crude glycerine was combined with either sodium monensin or essential oil, there was a reduction in DM, NDF and STC intake and an increase in DM and CP degradability of the diets. The adding crude glycerine to essential oil diets reduced the CH4 production. Sodium monensin treatments reduced DM and NDF intake and the production of total gas, CH4 , total VFA and acetic acid concentration. In conclusion, the adding crude glycerine (200 g/kg DM) with either sodium monensin (0.03 g/kg DM) or essential oil (0.5 g/kg DM) can be utilized in diets for Nellore cattle without causing detrimental effects on feed intake and improving the DM degradability.


Assuntos
Ração Animal/análise , Bovinos/fisiologia , Dieta/veterinária , Ingestão de Alimentos/efeitos dos fármacos , Glicerol/farmacologia , Rúmen/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão/efeitos dos fármacos , Digestão/fisiologia , Ácidos Graxos Voláteis , Glicerol/administração & dosagem , Abrigo para Animais , Monensin/administração & dosagem , Óleos Voláteis/administração & dosagem
19.
Int J Pharm ; 567: 118460, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31247278

RESUMO

As a new strategy for treatment of ductal carcinoma in situ, biocompatible and bioadhesive nanoemulsions for intraductal administration of the cytotoxic agent piplartine (piperlongumine) were optimized in this study. To confer bioadhesive properties, the nanoemulsion was modified with chitosan or hyaluronic acid. Tricaprylin was selected as the nanoemulsion non-polar phase due to its ability to dissolve larger drug amounts compared to isopropyl myristate and monocaprylin. Use of phosphatidylcholine as sole surfactant did not result in a homogeneous nanoemulsion, while its association with polysorbate 80 and glycerol (in a surfactant blend) led to the formation of nanoemulsions with droplet size of 76.5 ±â€¯1.2 nm. Heating the aqueous phase to 50 °C enabled sonication time reduction from 20 to 10 min. Inclusion of either chitosan or hyaluronic acid resulted in nanoemulsions with similar in vitro bioadhesive potential, and comparable ability to prolong mammary tissue retention (to 120 h) in vivo without causing undesirable histological alterations. Piplartine was stable in both nanoemulsions for 60 days; however, the size of loaded NE-HA was maintained at a similar range for longer periods of time, suggesting that this nanoemulsion may be a stronger candidate for intraductal delivery.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Dioxolanos/administração & dosagem , Glândulas Mamárias Animais/metabolismo , Nanopartículas/administração & dosagem , Piperidonas/administração & dosagem , Adesividade , Animais , Antineoplásicos Fitogênicos/química , Galinhas , Quitosana/administração & dosagem , Quitosana/química , Membrana Corioalantoide/efeitos dos fármacos , Dioxolanos/química , Vias de Administração de Medicamentos , Emulsões , Feminino , Glicerol/administração & dosagem , Glicerol/química , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Nanopartículas/química , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/química , Piperidonas/química , Polissorbatos/administração & dosagem , Polissorbatos/química , Ratos Wistar , Pele/química , Suínos
20.
Physiol Rep ; 7(10): e14093, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31140749

RESUMO

Electronic cigarette uses propylene glycol and glycerol to deliver nicotine and flavors to the lungs. Given the hundreds of different brands, the thousands of flavors available and the variations in nicotine concentrations, it is likely that electronic cigarette settings and e-liquid composition affect the size distribution of particles emitted and ultimately pulmonary deposition. We used the inExpose e-cigarette extension to study two separate modes of operation of electronic cigarettes, namely power-controlled and the temperature-controlled. We also assessed several e-liquids based on propylene glycol and glycerol concentrations, nicotine content, and selected monomolecular flavoring agents (menthol, vanillin, and maltol). Particle size distribution was measured using a Condensation Particle Counter and a Scanning Mobility Particle Sizer spectrometer. Lung deposition was predicted using the International Commission on Radiological Protection model. For all resistance coils, increase in power delivery generated larger particles while maintaining a higher coil temperature generated smaller particles. Increase in glycerol concentration led to the generation of larger particles. With regard to flavors, we showed that despite minor effect of menthol and maltol, vanillin dramatically increased particle size. Presence of nicotine also increased particle size. Finally, particles emitted by the electronic cigarette were predicted to mainly deposit in the alveoli and conditions generating larger particle sizes led to a reduction in predicted lung deposition. This study shows that coil temperature, propylene glycol and glycerol concentrations, presence of nicotine, and flavors affect the size of particles emitted by an electronic cigarette, directly affecting predicted lung deposition of these particles.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Pulmão/metabolismo , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Temperatura , Vaping , Administração por Inalação , Aerossóis , Desenho de Equipamento , Aromatizantes/administração & dosagem , Aromatizantes/química , Aromatizantes/metabolismo , Glicerol/administração & dosagem , Glicerol/química , Glicerol/metabolismo , Humanos , Modelos Biológicos , Nicotina/química , Nicotina/metabolismo , Agonistas Nicotínicos/química , Agonistas Nicotínicos/metabolismo , Tamanho da Partícula , Propilenoglicol/administração & dosagem , Propilenoglicol/química , Propilenoglicol/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA