Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Clin Infect Dis ; 73(5): 775-782, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-33580234

RESUMO

BACKGROUND: To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes. METHODS: Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at 6 months. RESULTS: The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a cutoff of 20 parasites/mL (area under the curve 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (ρ = 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a > 80% power to detect a difference in cure rate between treatment regimens if this difference was high (> 50%) and when minimally 30 patients were included per regimen. CONCLUSIONS: Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.


Assuntos
Leishmaniose Visceral , Parasitos , África Oriental , Animais , Biomarcadores , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Carga Parasitária
2.
Clin Infect Dis ; 68(9): 1530-1538, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30188978

RESUMO

BACKGROUND: Convenient, safe, and effective treatments for visceral leishmaniasis in Eastern African children are lacking. Miltefosine, the only oral treatment, failed to achieve adequate efficacy, particularly in children, in whom linear dosing (2.5 mg/kg/day for 28 days) resulted in a 59% cure rate, with lower systemic exposure than in adults. METHODS: We conducted a Phase II trial in 30 children with visceral leishmaniasis, aged 4-12 years, to test whether 28 days of allometric miltefosine dosing safely achieves a higher systemic exposure than linear dosing. RESULTS: Miltefosine accumulated during treatment. Median areas under the concentration time curve from days 0-210 and plasma maximum concentration values were slightly higher than those reported previously for children on linear dosing, but not dose-proportionally. Miltefosine exposure at the start of treatment was increased, with higher median plasma concentrations on day 7 (5.88 versus 2.67 µg/mL). Concentration-time curves were less variable, avoiding the low levels of exposure observed with linear dosing. The 210-day cure rate was 90% (95% confidence interval, 73-98%), similar to that previously described in adults. There were 19 treatment-related adverse events (AEs), but none caused treatment discontinuation. There were 2 serious AEs: both were unrelated to treatment and both patients were fully recovered. CONCLUSIONS: Allometric miltefosine dosing achieved increased and less-variable exposure than linear dosing, though not reaching the expected exposure levels. The new dosing regimen safely increased the efficacy of miltefosine for Eastern African children with visceral leishmaniasis. Further development of miltefosine should adopt allometric dosing in pediatric patients. CLINICAL TRIALS REGISTRATION: NCT02431143.


Assuntos
Antiprotozoários/farmacocinética , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , África Oriental , Antiprotozoários/sangue , Antiprotozoários/farmacologia , Área Sob a Curva , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/crescimento & desenvolvimento , Leishmania donovani/patogenicidade , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Masculino , Segurança do Paciente , Fosforilcolina/sangue , Fosforilcolina/farmacocinética , Fosforilcolina/farmacologia , Resultado do Tratamento
3.
J Sci Food Agric ; 99(5): 2186-2193, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30315585

RESUMO

BACKGROUND: Sunflower seed derived butter can be a source of protein and phenolic antioxidants in refrigerated dough. Chlorogenic quinone-amino acid induced greening can however occur at alkaline pH, which could result in less bioavailable conjugated phenol-amino acids. Acidulants were tested as potential anti-greening ingredients in refrigerated chemically leavened cookie dough. Effect of refrigerated storage time, leavening agents and acidulants on tryptophan fluorescence (λex = 280 nm, λem = 300-500 nm), color (hunter L*, a*, b* color scale), reducing capacity [1,1'-diphenyl-2-picryl-hydrazyl (DPPH) and Folin-Ciocalteu reducing capacity (FCRC)], and hydroxycinnamic acids were measured. RESULTS: The pH range of acidified doughs was 4.83-6.98 compared to 7.65-9.18 in non-acidified leavened doughs after 24 days. Greening was higher in baking soda dough control (a* = -0.54) than baking powder dough control (a* = 2.98) after 24 days, attributed to higher pH (9.18) of the former compared to pH 7.14 in the later. Tryptophan fluorescence intensity in baking soda dough decreased in the order: control > glucono-delta lactone ≈ citric acid after 24 days. The DPPH and FCRC of acidified doughs were greater than corresponding control doughs. CONCLUSION: The use of acidulants would prevent greening in sunflower dough without lowering its phenolic concentration, making use of sunflower butter in refrigerated dough for baked goods feasible. © 2018 Society of Chemical Industry.


Assuntos
Manteiga/análise , Helianthus/química , Triptofano/química , Temperatura Baixa , Farinha/análise , Fluorescência , Manipulação de Alimentos , Armazenamento de Alimentos , Concentração de Íons de Hidrogênio , Refrigeração , Lanches , Bicarbonato de Sódio/química
4.
J Food Sci Technol ; 55(4): 1478-1488, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29606762

RESUMO

Chlorogenic acid (CGA) binding to proteins in alkaline conditions results in the production of green trihydroxy benzacradine (TBA) derivatives. The formation of TBA derivatives could decrease product quality due to the potential losses in soluble protein and antioxidants and the production of an undesirable green color. To determine how cookie formulation affected the formation of TBA derivatives in sunflower butter cookies, two egg replacers (chia and banana) and two baking temperatures (162.8 and 190.6 °C) were used. Moisture, greening intensity, CGA content and antioxidant capacity were measured. Cookies made with egg and baked at 162.8 °C had the highest moisture, internal greening intensity, and TBA derivative formation, in addition to lower CGA content and antioxidant capacity. Cookies made with banana baked at 190.6 °C produced the opposite outcome with 35, 4, and 23% less internal greening, moisture, and TBA derivatives, respectively, and 90 and 76% higher CGA and antioxidant capacity. Internal greening was positively correlated with moisture and adduct concentration, and negatively correlated with spread factor and CGA content. Moisture had a significant impact on greening, which indicates that baking temperature and cookie dough formulation can be modified to produce a less green cookie with more unreacted antioxidants and protein.

5.
Lancet ; 386(9988): 56-62, 2015 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-25911172

RESUMO

BACKGROUND: Duration of bladder catheterisation after female genital fistula repair varies widely. We aimed to establish whether 7 day bladder catheterisation was non-inferior to 14 days in terms of incidence of fistula repair breakdown in women with simple fistula. METHODS: In this randomised, controlled, open-label, non-inferiority trial, we enrolled patients at eight hospitals in the Democratic Republic of the Congo, Ethiopia, Guinea, Kenya, Niger, Nigeria, Sierra Leone, and Uganda. Consenting patients were eligible if they had a simple fistula that was closed after surgery and remained closed 7 days after surgery, understood study procedures and requirements, and agreed to return for follow-up 3 months after surgery. We excluded women if their fistula was not simple or was radiation-induced, associated with cancer, or due to lymphogranuloma venereum; if they were pregnant; or if they had multiple fistula. A research assistant at each site randomly allocated participants 1:1 (randomly varying block sizes of 4-6; stratified by country) to 7 day or 14 day bladder catheterisation (via a random allocation sequence computer generated centrally by WHO). Outcome assessors were not masked to treatment assignment. The primary outcome was fistula repair breakdown, on the basis of dye test results, any time between 8 days after catheter removal and 3 months after surgery. The non-inferiority margin was 10%, assessed in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01428830. FINDINGS: We randomly allocated 524 participants between March 7, 2012, and May 6, 2013; 261 in the 7 day group and 263 in the 14 day group. In the per-protocol analysis, ten (4%) of 250 patients had repair breakdown in the 7 day group (95% CI 2-8) compared with eight (3%) of 251 (2-6) in the 14 day group (risk difference 0·8% [95% CI -2·8 to 4·5]), meeting the criteria for non-inferiority. INTERPRETATION: 7 day bladder catheterisation after repair of simple fistula is non-inferior to 14 day catheterisation and could be used for management of women after repair of simple fistula with no evidence of a significantly increased risk of repair breakdown, urinary retention, or residual incontinence up to 3 months after surgery. FUNDING: US Agency for International Development.


Assuntos
Cuidados Pós-Operatórios/métodos , Cateterismo Urinário/métodos , Fístula Urinária/cirurgia , Fístula Vaginal/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Falha de Tratamento , Adulto Jovem
6.
Compr Rev Food Sci Food Saf ; 15(5): 829-843, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33401798

RESUMO

Sunflower seeds are used to produce oil for human consumption, but its protein meal by-product has long been used as animal feed. Formation of green-colored complexes through oxidized chlorogenic acid(CGA)-protein interactions is a primary reason why defatted sunflower protein has not been widely utilized by the food industry. Sunflower protein possesses many properties that make it an appealing alternative protein source from both a marketing and formulation perspective, including its low cost, absence of major allergens, low antitrypsin inhibitors, and its status as both vegan and "clean" label friendly. With the global demand for sunflower oil and novel protein sources expected to increase and waste recovery a concern for many, providing uses for the sunflower meal and its fiber and polyphenol components would provide added value to by-products from sunflower oil processing. This review addresses the unique green pigmentation associated with the interaction of sunflower protein and oxidized CGA by outlining the sunflower oil and protein meal market, CGA reactions contributing to greening, methods for CGA extraction, and the effect of processing on sunflower protein quality and the greening reaction. This review also addresses potential food applications of sunflower protein-based ingredients, such as addition of texturized protein to food products; a microencapsulation matrix for antioxidants; edible, flexible biodegradable films; and even use of sunflower butter as an alternative to peanut butter where the green color is not considered undesirable. Continued studies are needed to make sunflower-based products and CGA-extraction processes available across the global marketplace.

7.
Food Res Int ; 147: 110574, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399547

RESUMO

Alkaline sunflower protein extraction can be performed along with de-phenolization of sunflower seed proteins if greening is unwanted. This greening is promoted at alkaline pH when chlorogenic acid (CGA) oxidizes and reacts with amino acids such as lysine. Thiol-containing dough conditioners: L-cysteine hydrochloride and glutathione (GSH) were investigated as an alternative de-greening strategy to acidification and de-phenolization. Greening and browning inhibition of thiols (GSH and Cysteine) were modeled by a combination of additive and interaction effects of extraction pH (7.0 to 11.0) and thiol concentration (0.00 to 5.60 mM) randomly assigned by Response Surface Methodology (RSM). The powders with the highest greening were the controls (pH 8.9-9.3 and no added thiols) and powders at pH 10.41 with 0.82 mM thiols. From RSM, the maximum greening inhibition was achieved at pH 8.71 and 4.23 mM cysteine, and pH 8.51 and 3.78 mM GSH. However, cysteine caused more browning at alkaline pH than GSH. Furthermore, fluorescence spectroscopy showed that cysteine had a protective effect against alkaline unfolding, whereas GSH quenched fluorescence in a concentration-dependent manner. Overall, de-greening of alkaline extracted sunflower protein was achieved by adding cysteine or glutathione, but the thiols differed in their contribution to the browning and unfolding effect.


Assuntos
Cisteína , Helianthus , Cisteína/metabolismo , Glutationa/metabolismo , Oxirredução , Proteínas/metabolismo
8.
Food Chem ; 309: 125697, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31727513

RESUMO

Formation of green trihydroxy benzacridine (TBA) derivatives when chlorogenic acid (CGA) quinones and amino acids react can be unappealing for some consumers. Cysteine was studied as an anti-greening strategy, given that cysteine-CGA conjugates are colorless. Buffered 2.55 mM CGA: 5.09 mM lysine: (0-5.09) mM cysteine solutions at pH 8 and 9 were prepared and incubated for a maximum of 48 h at 22 C. Color intensity and conjugate formation was monitored spectrophotometrically, and by HPLC and LC-MS respectively, while antioxidant capacity was measured by Folin-Ciolcateau and Trolox equivalent antioxidant capacity assays. Green TBA formation was promoted at higher pH and inhibited as cysteine concentration increased. Concentration-dependent cysteine inhibition of CGA-lysine greening was attributed to redox diphenol regeneration and formation of cysteinyl-CGA conjugates, which also contributed to antioxidant capacity. pH had a greater effect on antioxidant capacity than added cysteine. Results suggested a potential anti-greening approach for alkaline CGA quinone-amine greening.


Assuntos
Antioxidantes/química , Benzoquinonas/química , Cisteína/química , Ácido Clorogênico/química , Cromatografia Líquida de Alta Pressão , Cor , Reação de Cicloadição , Concentração de Íons de Hidrogênio , Espectrometria de Massas , Oxirredução
9.
J Food Prot ; 72(12): 2508-16, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20003732

RESUMO

Heat treatment can affect antimicrobial activity of plant by-products by altering phenolic content and composition and forming melanoidins. The antilisterial efficacy of heat-treated and unheated lyophilized pomegranate juice (LPJ) was determined. The LPJ was heated at 100 degrees C for 0, 30, 60, or 120 min and added at 2% (wt/wt) to ground top round beef, which was then cooked and inoculated with individual L. monocytogenes strains. Samples of meat stored at 5 degrees C were taken at days 1, 8, 14, and 21 and plated onto Oxford medium for enumeration of bacteria. The MIC of LPJ was determined, and agar well diffusion assays were conducted. Against five L. monocytogenes strains, LPJ had a MIC of 1.50 to 1.75% (wt/vol) and 16.8- to 20.0-mm zones of inhibition. In general, no significant differences in L. monocytogenes levels between the various treatments, including the commercial sodium lactate-sodium diacetate combination, were detected at days 1 and 8. The LPJ (0, 30, 60, and 120 min of heating) significantly inhibited growth of all five L. monocytogenes strains in refrigerated ground cooked beef by 1.80 to 4.61 log CFU/g at day 21. Heating did not negatively impact LPJ antilisterial activity. Addition of LPJ lowered pH values by 0.3 units. The L*, a*, and b* values of cooked ground beef with LPJ changed during the study by 3.4 to 4.43, 0.44 to 0.8, and 0.57 to 1.36 units, respectively, compared with the control. This is the first investigation to confirm pomegranate's antilisterial activity in vitro and in ground beef.


Assuntos
Microbiologia de Alimentos , Listeria monocytogenes/efeitos dos fármacos , Lythraceae/química , Carne/microbiologia , Extratos Vegetais/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bovinos , Colorimetria , Manipulação de Alimentos , Liofilização , Temperatura Alta , Concentração de Íons de Hidrogênio , Extratos Vegetais/química
10.
J Chromatogr A ; 1192(2): 259-65, 2008 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-18407280

RESUMO

A rapid negative ion ESI high-performance capillary liquid chromatography-mass spectrometry method was developed to identify and quantify flavonoids (e.g., flavanols, flavonols, flavanones and glycosides). Fifteen standards and two varieties of almond skin extract powder (Carmel and Nonpareil) were used to demonstrate the chromatographic separation, reproducibility and accuracy of the method that employed a 150 mm x 0.3 mm ChromXP 3C18-EP-120 column. All standards eluted in less than 10 min, providing a 9-12x reduction in analysis time compared to existing methods (90-120 min). However, isomers (e.g., catechin/epicatechin and galactosides/glucosides) were not resolved and, therefore, identified and quantified collectively. RSDs for retention time and peak area reproducibility (mass spectrometry data) were <0.5% and <5.0%, respectively. Peak area reproducibility was greatly improved (from a RSD>10%) after the implementation of a low-flow metal needle in the ESI source. Quantitation by mass spectrometry also afforded a % error less than 5% for most compounds.


Assuntos
Flavonoides/análise , Prunus/química , Eletrocromatografia Capilar , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Padrões de Referência , Reprodutibilidade dos Testes , Solventes , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA