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1.
Br J Community Nurs ; 29(4): 162-170, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38564442

ABSTRACT

Home enteral tube feeding (HEF) has many benefits and is largely safe practice. Some complications have historically required intervention in the acute setting, including traumatic displacement of feeding tubes (i.e. internal bumper/balloon removed intact), and evidence to support the safe replacement of these tubes in the community is lacking. To address this, a service enabling community homecare nurses (CHN) to replace traumatically displaced feeding tubes was designed and evaluated. Adult patients presenting with a traumatically displaced feeding tube over 29 months were included in the service evaluation. Baseline characteristics and outcomes at day 1, 7 and 6 months post-replacement were recorded. A total of 71 tube replacements were performed by CHNs in 60 patients. No clinical complications were recorded at any follow-up points. A simple cost analysis estimated savings of £235 754.40. These results suggest that nurse-led replacement of traumatically displaced feeding tubes in adults in the community is low-risk and offers potential cost savings.


Subject(s)
Gastrostomy , Nurses , Adult , Humans , Nurse's Role , Enteral Nutrition/methods , Intubation, Gastrointestinal
2.
Epilepsia Open ; 9(2): 727-738, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38411329

ABSTRACT

OBJECTIVE: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. METHODS: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8-46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. RESULTS: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). SIGNIFICANCE: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. PLAIN LANGUAGE SUMMARY: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.


Subject(s)
Diet, Ketogenic , Drug Resistant Epilepsy , Child , Adult , Humans , Young Adult , Diet, Ketogenic/adverse effects , Diet, Ketogenic/methods , Quality of Life , Triglycerides , Seizures , Carbohydrates
3.
Nutr Clin Pract ; 39(2): 437-449, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37635446

ABSTRACT

BACKGROUND: Enteral tube feeding can require considerable amounts of plastic equipment including delivery sets and containers, often disposed of after a single feeding session because of bacterial contamination concerns. The aim of this research was to assess whether reuse of delivery sets and containers for up to 24 h is safe from a microbiological perspective. METHODS: Four enteral tube feeding systems (FS) were tested under hygienic controlled or repeated inoculation challenge conditions using key foodborne pathogens, to assess bacterial growth over time (FS1: ready-to-hang, closed 1-L system with delivery set reused, stored at room temperature [RT]; FS2: a prepared, powdered, open 1-L system with delivery set and container reused, stored at RT; FS3 and FS4: prepared, powdered, open 200-ml bolus systems with delivery set and container reused, stored at RT [FS3] and refrigeration [FS4]). Feed samples were cultured at 0.5, 6.5, 12.5, 18.5, and 24.5 h with >2 Δlog considered significant bacterial growth. RESULTS: Under hygienic control, FS1, FS3, and FS4 were below the level of enumeration (<5 CFU/g) for all bacteria tested, at all time points. In FS2, significant bacterial growth was observed from 18.5 h. Under repeated bacterial inoculation challenge, no significant growth was observed in FS1 and FS4 over 24.5 h; however, significant growth was observed in FS2 after 6.5 h and in FS3 after 10-12 h. CONCLUSION: With hygienic handling technique, there is limited bacterial growth with reuse of delivery sets and containers over 24 h. Refrigeration between feeding sessions and using boluses of reconstituted powdered feed reduce bacterial growth risk.


Subject(s)
Enteral Nutrition , Equipment Contamination , Humans , Enteral Nutrition/methods , Equipment Contamination/prevention & control , Bacteria , Refrigeration , Food Microbiology
4.
Front Nutr ; 10: 1297624, 2023.
Article in English | MEDLINE | ID: mdl-38024371

ABSTRACT

Introduction: There is an emerging need for plant-based, vegan options for patients requiring nutritional support. Methods: Twenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed. Results: Patients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition ('MUST' score ≥ 2) reduced from 20 to 16 patients (p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p < 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study (p > 0.06) with no serious adverse events related. Discussion: This study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition.

5.
Nutrients ; 15(16)2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37630769

ABSTRACT

(1) Background: Good adherence to a Phe-restricted diet supplemented with an adequate amount of a protein substitute (PS) is important for good clinical outcomes in PKU. Glycomacropeptide (cGMP)-PSs are innovative, palatable alternatives to amino acid-based PSs (AA-PS). This study aimed to evaluate a new cGMP-PS in liquid and powder formats in PKU. (2) Methods: Children and adults with PKU recruited from eight centres were prescribed at least one serving/day of cGMP-PS for 7-28 days. Adherence, acceptability, and gastrointestinal tolerance were recorded at baseline and the end of the intervention. The blood Phe levels reported as part of routine care during the intervention were recorded. (3) Results: In total, 23 patients (powder group, n = 13; liquid group, n = 10) completed the study. The majority assessed the products to be palatable (77% of powder group; 100% of liquid group) and well tolerated; the adherence to the product prescription was good. A total of 14 patients provided blood Phe results during the intervention, which were within the target therapeutic range for most patients (n = 11) at baseline and during the intervention. (4) Conclusions: These new cGMP-PSs were well accepted and tolerated, and their use did not adversely affect blood Phe control.


Subject(s)
Caseins , Peptide Fragments , Adult , Child , Humans , Powders , Dietary Supplements , Cyclic GMP
6.
Nutrients ; 15(16)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37630788

ABSTRACT

(1) Background: Poor palatability, large volume, and lack of variety of some liquid and powdered protein substitutes (PSs) for patients with phenylketonuria (PKU) and tyrosinemia (TYR) can result in poor adherence. This study aimed to evaluate a new unflavoured, powdered GMP-based PS designed to be mixed into drinks, foods, or with other PSs, in patients with PKU and TYR. (2) Methods: Paediatric and adult community-based patients were recruited from eight metabolic centres and prescribed ≥1 sachet/day (10 g protein equivalent (PE)) of the Mix-In-style PS over 28 days. Adherence, palatability, GI tolerance, and metabolic control were recorded at baseline and follow-up. Patients who completed at least 7 days of intervention were included in the final analysis. (3) Results: Eighteen patients (3-45 years, nine males) with PKU (n = 12) and TYR (n = 6) used the Mix-In-style PS for ≥7 days (mean 26.4 days (SD 4.6), range 11-28 days) alongside their previous PS, with a mean intake of 16.7 g (SD 7.7) PE/day. Adherence was 86% (SD 25), and GI tolerance was stable, with n = 14 experiencing no/no new symptoms and n = 3 showing improved symptoms compared to baseline. Overall palatability was rated satisfactory by 78% of patients, who successfully used the Mix-In-style PS in various foods and drinks, including smoothies, squash, and milk alternatives, as a top-up to meet their protein needs. There was no concern regarding safety/metabolic control during the intervention. (4) Conclusions: The 'Mix-In'-style PS was well adhered to, accepted, and tolerated. Collectively, these data show that providing a flexible, convenient, and novel format of PS can help with adherence and meet patients' protein needs.


Subject(s)
Phenylketonurias , Tyrosinemias , Glycoproteins/adverse effects , Glycoproteins/therapeutic use , Glycopeptides/adverse effects , Glycopeptides/therapeutic use , Phenylketonurias/diet therapy , Humans , Male , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Tyrosinemias/diet therapy , Treatment Outcome , Gastrointestinal Tract/metabolism , Food , Beverages
7.
Immun Inflamm Dis ; 10(6): e636, 2022 06.
Article in English | MEDLINE | ID: mdl-35634950

ABSTRACT

BACKGROUND: Healthy gut microbiota is important for prognosis in cow's milk allergy (CMA). The application of synbiotics (specific pre- and probiotics) in extensively hydrolyzed formulae (eHFs) is a relatively new concept. AIMS: To evaluate a synbiotic-containing, whey-based eHF (SeHF) with galacto-oligosaccharides, fructo-oligosaccharides, and bifidobacterium breve M-16V in infants with CMA. MATERIALS AND METHODS: A 31-day one-arm pilot study in 29 infants with CMA (mean age 30.8 weeks [SD 11]) was undertaken, with outcomes including gastrointestinal tolerance, atopic dermatitis symptoms, dietary intake, growth, SeHF acceptability, caregiver quality of life, and hospital-related healthcare use. RESULTS: Significant improvements (p < .05) in the severity of abdominal pain (in 57%), burping (in 46%), flatulence (in 79%), constipation (in 14%), rhinitis (41%), and itchy eyes (73%), as well as atopic dermatitis in those with severe baseline symptoms (PO-SCORAD© reduction: 34.7-18.2 (p = .003), n = 6) were observed over time. Growth and caregiver quality of life scores significantly increased (+26.7%, p < .05) over time. Hospital visits and medications significantly reduced (-1.61 and -2.23, respectively, p < .005) in the 6 months after SeHF initiation. DISCUSSION: In this small, single-arm, pilot study, the use of SeHF enhanced the management of infants with non-IgE mediated CMA who were already established on eHF. CONCLUSION: Whilst this study adds to the evidence base for the use of SeHF in CMA, further robust research to explore the longer-term benefits of synbiotics, specifically the blend used in this study, for the clinical management of infants with CMA is warranted.


Subject(s)
Dermatitis, Atopic , Milk Hypersensitivity , Synbiotics , Animals , Caregivers , Cattle , Delivery of Health Care , Female , Hospitals , Humans , Milk Hypersensitivity/therapy , Oligosaccharides , Pilot Projects , Quality of Life
8.
Eur J Pediatr ; 179(9): 1421-1430, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32170451

ABSTRACT

Children with or at risk of faltering growth require nutritional support and are often prescribed oral nutritional supplements (ONS). This randomised controlled trial investigated the effects of energy-dense paediatric ONS (2.4 kcal/ml, 125 ml: cONS) versus 1.5 kcal/ml, 200 ml ONS (sONS) in community-based paediatric patients requiring oral nutritional support. Fifty-one patients (mean age 5.8 years (SD 3)) with faltering growth and/or requiring ONS to meet their nutritional requirements were randomised to cONS (n = 27) or sONS (n = 24) for 28 days. Nutrient intake, growth, ONS compliance and acceptability, appetite and gastro-intestinal tolerance were assessed. Use of the cONS resulted in significantly greater mean total daily energy (+ 531 kcal/day), protein (+ 10.1 g/day) and key micronutrient intakes compared with the sONS group at day 28 and over time, due to high ONS compliance (81% of patients ≥ 75%), maintained intake from diet alone and improved appetite in the cONS group, compared with the sONS group. Although growth increased in both intervention groups, results were significant in the cONS group (weight (p = 0.007), height (p < 0.001) and height z-score (p = 0.006)).Conclusions: This study shows that use of energy-dense (2.4 kcal/ml) low-volume paediatric-specific ONS leads to improved nutrient intakes, growth and appetite in paediatric patients requiring oral nutrition support compared with standard energy density ONS.Trial registration: The trial is registered at clinicaltrials.gov , identification number NCT02419599. What is Known: • Faltering growth is the failure of children to achieve adequate growth at a normal rate for their age and requires nutritional support, including the use of oral nutritional supplements (ONS). • Energy-dense, low-volume ONS have benefits over standard ONS in adults. What is New: • This is the first RCT to investigate the effects of energy-dense, low-volume ONS (2.4 kcal/ml, 125 ml) in children with faltering growth, showing significant improvements in total nutrient intake and increased growth. • Energy-dense, low-volume ONS can play a key role in the management of faltering growth.


Subject(s)
Malnutrition , Adult , Child , Child, Preschool , Dietary Supplements , Eating , Energy Intake , Humans , Pilot Projects
9.
Br J Nutr ; 122(11): 1271-1278, 2019 12 14.
Article in English | MEDLINE | ID: mdl-31782379

ABSTRACT

Anecdotal evidence suggests the use of bolus tube feeding is increasing in the long-term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from ten centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding (n 604, 60 % male, age 58 years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients' complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37 %). Patients were long-term tube fed (4·1 years tube feeding, 3·5 years bolus tube feeding), living at home (71 %) and sedentary (70 %). The majority were head and neck cancer patients (22 %) who were significantly more active (79 %) and lived at home (97 %), while those with cerebral palsy (12 %) were typically younger (age 31 years) but sedentary (94 %). Most patients used bolus feeding as their sole feeding method (46 %), because it was quick and easy to use, as a top-up to oral diet or to mimic mealtimes. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85 % of patients, with 51 % of these being compact-style ONS (2·4 kcal (10·0 kJ)/ml, 125 ml). This survey shows that bolus tube feeding is common among UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.


Subject(s)
Enteral Nutrition/methods , Enteral Nutrition/statistics & numerical data , Home Care Services/statistics & numerical data , Surveys and Questionnaires , Adult , Aged , Aged, 80 and over , Cerebral Palsy/therapy , Cross-Sectional Studies , Female , Head and Neck Neoplasms/therapy , Humans , Male , Middle Aged , United Kingdom
10.
Immun Inflamm Dis ; 7(4): 292-303, 2019 12.
Article in English | MEDLINE | ID: mdl-31692292

ABSTRACT

INTRODUCTION: Eosinophilic oesophagitis (EoE) is an immune-mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE. METHODS: Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications. RESULTS: Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%-100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%-81% and 40%-69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long-term impacts of each diet were not thoroughly explored. CONCLUSIONS: The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long-term management.


Subject(s)
Amino Acids/therapeutic use , Eosinophilic Esophagitis/diet therapy , Food, Formulated , Milk Hypersensitivity/diet therapy , Child , Child, Preschool , Female , Humans , Infant , Male
11.
Clin Nutr ; 31(3): 293-312, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22257636

ABSTRACT

BACKGROUND & AIMS: Oral nutritional supplements (ONS) play a key role in the management of malnutrition. This systematic review examined patients' compliance with ONS across healthcare settings and the influence of patient and ONS-related factors. METHODS: A systematic review identified 46 studies (n = 4328) of ONS in which data on compliance (% of prescribed quantity of ONS consumed) was available. Pooled mean %compliance was assessed overall and according to study design and healthcare setting. Inter-relationships between compliance and ONS-related and patient-related factors, and total energy intake were assessed. RESULTS: Overall mean compliance with ONS was 78% (37%-100%; 67% hospital, 81% community; overall mean ONS intake 433 kcal/d). Percentage compliance was similar in randomised (79%) and non-randomised (77%) trials, with little variation between diagnostic groups. Compliance across a heterogeneous group of unmatched studies was positively associated with higher energy-density ONS and greater ONS and total energy intakes, negatively associated with age, and unrelated to amount or duration of ONS prescription. CONCLUSIONS: This systematic review suggests that compliance to ONS is good, especially with higher energy-density ONS, resulting in improvements in patients' total energy intakes that have been linked with clinical benefits. Further research is required to address the compliance and effectiveness of other common methods of oral nutritional support.


Subject(s)
Dietary Supplements , Food, Formulated , Malnutrition/diet therapy , Patient Compliance , Adult , Age Factors , Dietary Supplements/analysis , Energy Intake , Food, Formulated/analysis , Humans
12.
Br J Nutr ; 96(3): 482-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16925853

ABSTRACT

Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate the possible inhibitory effects of quercetin ingestion from a dietary source on collagen-stimulated platelet aggregation and signalling. A double-blind randomised cross-over pilot study was undertaken. Subjects ingested a soup containing either a high or a low amount of quercetin. Plasma quercetin concentrations and platelet aggregation and signalling were assessed after soup ingestion. The high-quercetin soup contained 69 mg total quercetin compared with the low-quercetin soup containing 5 mg total quercetin. Plasma quercetin concentrations were significantly higher after high-quercetin soup ingestion than after low-quercetin soup ingestion and peaked at 2.59 (sem 0.42) mumol/l. Collagen-stimulated (0.5 mug/ml) platelet aggregation was inhibited after ingestion of the high-quercetin soup in a time-dependent manner. Collagen-stimulated tyrosine phosphorylation of a key component of the collagen-signalling pathway via glycoprotein VI, Syk, was significantly inhibited by ingestion of the high-quercetin soup. The inhibition of Syk tyrosine phosphorylation was correlated with the area under the curve for the high-quercetin plasma profile. In conclusion, the ingestion of quercetin from a dietary source of onion soup could inhibit some aspects of collagen-stimulated platelet aggregation and signalling ex vivo. This further substantiates the epidemiological data suggesting that those who preferentially consume high amounts of quercetin-containing foods have a reduced risk of thrombosis and potential CVD risk.


Subject(s)
Collagen/physiology , Eating/physiology , Fibrinolytic Agents/administration & dosage , Onions/chemistry , Platelet Activation/physiology , Platelet Aggregation/physiology , Quercetin/administration & dosage , Adult , Cross-Over Studies , Diet , Disaccharides/blood , Double-Blind Method , Female , Flavonoids/analysis , Flavonols/blood , Humans , Male , Pilot Projects , Quercetin/analogs & derivatives , Quercetin/blood , Signal Transduction/physiology
13.
Blood ; 105(4): 1500-7, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15466936

ABSTRACT

Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57. Recent evidence supports an alternative role for this family of proteins on the surface of cells, where they are involved in receptor remodeling and recognition. In platelets, blocking PDI with inhibitory antibodies inhibits a number of platelet activation pathways, including aggregation, secretion, and fibrinogen binding. Analysis of human platelet membrane fractions identified the presence of the thiol isomerase protein ERP5. Further study showed that ERP5 is resident mainly on platelet intracellular membranes, although it is rapidly recruited to the cell surface in response to a range of platelet agonists. Blocking cell-surface ERP5 using inhibitory antibodies leads to a decrease in platelet aggregation in response to agonists, and a decrease in fibrinogen binding and P-selectin exposure. It is possible that this is based on the disruption of integrin function, as we observed that ERP5 becomes physically associated with the integrin beta(3) subunit during platelet stimulation. These results provide new insights into the involvement of thiol isomerases and regulation of platelet activation.


Subject(s)
Blood Platelets/enzymology , Blood Platelets/physiology , Protein Disulfide-Isomerases/physiology , Amino Acid Sequence , Antibodies, Blocking/pharmacology , Cell Membrane/enzymology , Cytoplasmic Granules/immunology , Cytoplasmic Granules/metabolism , Fibrinogen/metabolism , Humans , Integrin beta3/metabolism , Intracellular Fluid/enzymology , Molecular Sequence Data , P-Selectin/metabolism , Platelet Activation/physiology , Platelet Aggregation Inhibitors/pharmacology , Protein Binding/physiology , Protein Disulfide-Isomerases/antagonists & inhibitors , Protein Disulfide-Isomerases/immunology , Protein Disulfide-Isomerases/isolation & purification , Protein Disulfide-Isomerases/metabolism
14.
Proc Nutr Soc ; 62(2): 469-78, 2003 May.
Article in English | MEDLINE | ID: mdl-14506895

ABSTRACT

Platelets play a substantial role in cardiovascular disease, and for many years there has been a search for dietary componentsthat are able to inhibit platelet function and therefore decrease the risk of cardiovasculardisease. Platelets can be inhibited by alcohol, dietary fats and some antioxidants, including agroup of compounds, the polyphenols, found in fruits and vegetables. A number of these compounds have been shown to inhibit platelet function both in vitro and in vivo. In the present study the effects of the hydroxycinnamates and the flavonoid quercetin on platelet activation and cell signalling in vitro were investigated. The hydroxycinnamates inhibited platelet function, although not at levels that can be achieved in human plasma by dietary intervention. However, quercetin inhibited platelet aggregation at levels lower than those previously reported. Quercetin was also found to inhibit intracellular Ca mobilisation and whole-cell tyrosine protein phosphorylation in platelets, which are both processes essential for platelet activation. The effect of polyphenols on platelet aggregation in vivo was also investigated. Twenty subjects followed a low-polyphenol diet for 3 d before and also during supplementation. All subjects were supplemented with a polyphenol-rich meal every lunchtime for 5d. Platelet aggregation and plasma flavonols were measured at baseline and after 5d of dietary supplementation. Total plasma flavonoids increased significantly after the dietary intervention period (P = 0.001). However, no significant changes in ex vivo platelet aggregation were observed. Further investigation of the effects of individual polyphenolic compoundson platelet function, both in vitro and in vivo, is required in order to elucidate their role in the relationship between diet and the risk of cardiovascular disease.


Subject(s)
Blood Platelets/drug effects , Cardiovascular Diseases/prevention & control , Flavonoids/pharmacology , Phenols/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Antioxidants/administration & dosage , Antioxidants/pharmacology , Blood Platelets/physiology , Calcium/blood , Cardiovascular Diseases/epidemiology , Flavonoids/administration & dosage , Fruit , Humans , Phenols/administration & dosage , Platelet Adhesiveness/drug effects , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Polyphenols , Quercetin/pharmacology , Vegetables
15.
Br J Nutr ; 89(5): 607-16, 2003 May.
Article in English | MEDLINE | ID: mdl-12720581

ABSTRACT

There has been much recent interest in the cardiovascular benefits of dietary isoflavones. The aim of the present in vitro studies was to investigate potential anti-thrombogenic and anti-atherogenic effects of the isoflavones genistein and daidzein in platelets, macrophages and endothelial cells. Pre-treatment with either isoflavone inhibited collagen-induced platelet aggregation in a dose-dependent manner. In a macrophage cell line (RAW 264.7) activated with interferon gamma plus lipopolysaccharide, both isoflavones were found to inhibit NO production and tumour necrosis factor alpha (TNF-alpha) secretion dose-dependently, but they did not affect mRNA levels for inducible nitric oxide synthase and cyclo-oxygenase-2. Both isoflavones also dose-dependently decreased monocyte chemoattractant protein-1 secretion induced by TNF-alpha in human umbilical vein endothelial cells. Compared with daidzein, genistein exerted greater inhibitory effects for all parameters studied. The present data contributes to our knowledge on the molecular mechanisms by which isoflavones may protect against coronary artery disease. Further studies are required to determine whether the effects of isoflavones observed in the current in vitro studies are relevant to the aetiology of coronary artery disease in vivo.


Subject(s)
Arteriosclerosis/prevention & control , Endothelium, Vascular/drug effects , Genistein/pharmacology , Isoflavones/pharmacology , Macrophages/drug effects , Platelet Aggregation/drug effects , Analysis of Variance , Animals , Arteriosclerosis/metabolism , Cell Line , Cells, Cultured , Chemokine CCL2/metabolism , Cyclooxygenase 2 , Dose-Response Relationship, Drug , Endothelium, Vascular/metabolism , Humans , Isoenzymes/metabolism , Macrophage Activation , Macrophages/metabolism , Membrane Proteins , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Prostaglandin-Endoperoxide Synthases/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/pharmacology
16.
Free Radic Biol Med ; 33(2): 220-35, 2002 Jul 15.
Article in English | MEDLINE | ID: mdl-12106818

ABSTRACT

Dietary polyphenols are widely considered to contribute to health benefits in humans. However, little is yet known concerning their bioactive forms in vivo and the mechanisms by which they may contribute toward disease prevention. Although many studies are focusing on the bioavailability of polyphenols through studying their uptake and the excretion of their conjugated forms, few are emphasizing the occurrence of metabolites in vivo formed via degradation by the enzymes of colonic bacteria and subsequent absorption. The purpose of this research was to investigate the relationship between biomarkers of the colonic biotransformation of ingested dietary polyphenols and the absorbed conjugated polyphenols. The results show that the majority of the in vivo forms derive from cleavage products of the action of colonic bacterial enzymes and subsequent metabolism in the liver. Those include the glucuronides of 3-hydroxyphenylacetic, homovanillic, vanillic and isoferulic acid as well as 3-(3-methoxy-4-hydroxyphenyl)-propionic, 3-(3-hydroxyphenyl)-propionic acid, and 3-hydroxyhippuric acid. In contrast, intact conjugated polyphenols themselves, such as the glucuronides of quercetin, naringenin and ferulic, p-coumaric, and sinapic acid were detected at much lower levels. The results suggest that consideration should be given to the cleavage products as having a putative role as physiologically relevant bioactive components in vivo.


Subject(s)
Diet , Flavonoids , Liver/metabolism , Phenols/metabolism , Polymers/metabolism , Adult , Biological Availability , Biotransformation , Chromatography, High Pressure Liquid , Female , Glucuronides/metabolism , Humans , Intestinal Absorption , Male , Mass Spectrometry , Middle Aged , Polyphenols
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