RESUMEN

Preclinical and early phase clinical studies suggest that an appropriately dosed umbilical cord blood (CB) infusion has the potential to help improve motor function in young children with cerebral palsy (CP). As many children with CP do not have their own CB available, use of allogeneic cells would extend access to this potentially beneficial therapy to more children. In this phase I, open-label study, 15 children, aged 1 to 6 years, with moderate to severe spastic CP were treated with a single intravenous infusion of allogeneic human leukocyte antigen (HLA) matched or partially matched sibling CB with a cell dose of ≥2.5 × 107 cells/kg based on the pre-cryopreservation count (median infused cell dose, 3.3 × 107 ; range, 1.8-5.2 × 107 ). There were a total of 49 adverse events (AEs) over a 2-year time period, but there were no AEs related to the CB infusions. Specifically, there were no acute infusion reactions and no antibody formation against platelets, red blood cells, or donor-specific HLA antigens. Donor cells were not detected in peripheral blood 6 months later. Six months after infusion, participants were assessed for response and experienced a mean ± SD increase of 4.7 ± 2.5 points on the Gross Motor Function Measure-66 and 1 ± 2.9 points on the Peabody Gross Motor Quotient. Appropriately dosed, allogeneic partially or fully HLA-matched sibling CB infusion is well tolerated and potentially beneficial in young children with CP.

Asunto(s)

Asunto(s)

RESUMEN

Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells. Sixteen adult patients received a prophylactic DLI at a median of 113 days (range 76-280 days) following an HLA-identical, non-myeloablative allogeneic hematopoietic stem cell transplantation. Three patients each received the naive T-cell depleted DLI with a CD3+ dose of 1 × 105/kg, 1 × 106/kg, and 5 × 106/kg. The maximum dose of 1 × 107/kg was expanded to 7 patients. No dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI were observed at any dose level. One patient developed grade 2 acute GvHD of skin and upper intestines, and another developed moderate chronic GvHD of the lungs following the DLI. With a median follow-up of 2.8 years, 2-year progression-free and overall survival is 50.0% and 68.8%, respectively. In conclusion, these data suggest that a DLI that has been depleted of CD45RA+ naive T cells is feasible and carries a low risk of acute or chronic GvHD.

Asunto(s)

RESUMEN

Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 106 cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD-specific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial.

Asunto(s)

RESUMEN

OBJECTIVE: To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD). STUDY DESIGN: This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion. RESULTS: CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power. CONCLUSIONS: Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.

Asunto(s)

RESUMEN

Introduction Achieving good glycemic control during enteral tube feeding in patients with diabetes mellitus can be difficult. National guidelines emphasize the need for the early involvement of the dietitian and diabetes specialist nurse, regular capillary blood glucose (CBG) monitoring, and the avoidance of hypoglycemic events. We aimed to assess glycemic control in patients with diabetes during enteral tube feeding. Materials and methods A retrospective study, involving patients with diabetes who had enteral tube feeding during their hospital stay from January to December 2016, was performed. Data included feed carbohydrate content, infusion rate and duration, involvement of dietitian and inpatient diabetes specialist nurse, capillary blood glucose monitoring, and documentation of hypoglycemic events. Results There were 40 patient episodes. Mean (range) age: 67 (29-94) years, 60% were male, 97.5% had type 2 diabetes, and 60% were on oral hypoglycemic agents prior to admission. The average feed carbohydrate content was 14.6 g/dL and the average feed rate was 73 ml/hour. Dietitians and diabetes inpatient specialist nurses (DISNs) were involved in 100% and 75% of cases, respectively. During enteral tube feeding, capillary blood glucose was controlled using metformin, subcutaneous insulin, or intravenous insulin in 30%, 42.5%, and 15% of cases, respectively. Capillary blood glucose was checked four to six hourly in 100% of cases. The target capillary blood glucose range (6-12 mmol/L) was achieved in 40% of cases. The minimum capillary blood glucose value (median (interquartile range)) was 4.9 (3.9-6.2) mmol/L and the maximum value was 15.1 (11.9-18.8) mmol/L. Using these lower and upper quartile values for minimum and maximum values, respectively, revealed that 57.5% of patients had a capillary blood glucose range of 3.9-18.8 mmol/L. Two patients had hypoglycemic events requiring treatment. Conclusions This study demonstrated that despite adequate adherence to our trust's guidelines for glycemic control during enteral tube feeding in patients with diabetes, the target glycemic range was achieved in 40% of cases. The importance of the early involvement of the diabetes inpatient specialist nurse cannot be overemphasized. Early initiation and proactive (daily) dose up-titration of insulin are required to improve glycemic control during enteral tube feeding. A national audit tool for glycemic control and mortality data during enteral tube feeding is required.

RESUMEN

BACKGROUND: The cell dose infused for cord blood transplantation strongly correlates with outcomes following transplantation. Post thaw recoveries can be improved by washing cord blood units (CBUs) in dextran/albumin. Early methods used a labor-intensive manual process. We have recently developed and validated an automated washing method. We now report our results of a study comparing cellular recoveries achieved after manual and automated wash, as well as the impact on engraftment following allogeneic transplantation. STUDY DESIGN AND METHODS: CBUs distributed by the Carolinas Cord Blood Bank for clinical use at Duke University after manual or automated wash were included in this report. Precryopreservation total nucleated cell count, total CD34+, colony-forming units, recoveries, and sterility were analyzed by wash method. Patient age, cell dose/weight, diagnosis, conditioning regimen, immunosuppression, and time to neutrophil engraftment were also analyzed. RESULTS: Manual and automated washed CBUs yielded similar total nucleated cell count and total CD34+ recoveries. Significantly higher colony-forming units recoveries were achieved after automated washing. Patients who received CBUs washed via an automated method experienced earlier neutrophil engraftment. CONCLUSION: While manual and automated washing achieved similar post thaw cellular recoveries, automated washed CBUs demonstrated higher colony-forming unit recovery, which is an important predictor of potency and engraftment. Furthermore, we demonstrated that automated washing was associated with earlier neutrophil engraftment. Our findings favor the use of an automated wash method over a manual approach.

Asunto(s)

RESUMEN

Cerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted a phase II trial of autologous cord blood (ACB) infusion in children with CP to test whether ACB could improve function (ClinicalTrials.gov, NCT01147653; IND 14360). In this double-blind, placebo-controlled, crossover study of a single intravenous infusion of 1-5 × 107 total nucleated cells per kilogram of ACB, children ages 1 to 6 years with CP were randomly assigned to receive ACB or placebo at baseline, followed by the alternate infusion 1 year later. Motor function and magnetic resonance imaging brain connectivity studies were performed at baseline, 1, and 2 years post-treatment. The primary endpoint was change in motor function 1 year after baseline infusion. Additional analyses were performed at 2 years. Sixty-three children (median age 2.1 years) were randomized to treatment (n = 32) or placebo (n = 31) at baseline. Although there was no difference in mean change in Gross Motor Function Measure-66 (GMFM-66) scores at 1 year between placebo and treated groups, a dosing effect was identified. In an analysis 1 year post-ACB treatment, those who received doses ≥2 × 107 /kg demonstrated significantly greater increases in GMFM-66 scores above those predicted by age and severity, as well as in Peabody Developmental Motor Scales-2 Gross Motor Quotient scores and normalized brain connectivity. Results of this study suggest that appropriately dosed ACB infusion improves brain connectivity and gross motor function in young children with CP. Stem Cells Translational Medicine 2017;6:2071-2078.

Asunto(s)

RESUMEN

BACKGROUND AIMS: Removing DMSO post-thaw results in: reduced infusion reactions, improved recovery and stability of viable CD34+ cells. Validated methods use 5%-8.3% Dextran 40 with 2.5%-4.2% HSA for this purpose. Recent shortages of clinical grade Dextran require identification of suitable alternatives. METHODS: PBPC were used to compare a standard 2X wash medium of 5 parts 10% Dextran 40 in saline (DEX) with 1 part 25% HSA (8.3% DEX/ 4.2% HSA) with Hydroxyethyl Starch (HES)-based solutions. Cells in replicate bags were diluted with an equal volume of wash solution, equilibrated 5 minutes, the bag filled with wash medium, pelleted and the supernatant expressed. Bags were restored to the frozen volume in wash medium and tested by single platform flow cytometry and CFU. Total viability, viable TNC, MNC, and CD34+ cell recovery, and CD34+ cell viability were compared immediately post-thaw and after 90 minutes. RESULTS: 5.2% HES/4.2% HSA did not differ from our standard in CD34 recovery or viability. Due to concerns that high concentrations of HES could affect renal function we tested 0.6% HES/2.5% HSA resulting in significantly poorer CD34 recovery and viability. Results improved using 2.4% HES/4.2% HSA and when 0.6% HES/4.2%HSA was used no significant differences were seen. CFU assays confirmed no differences between the standard dextran arm and HES at 2.4% or 0.6% so long as HSA was at 4.2%. CONCLUSIONS: We conclude that HES from 0.6% to 5.2% with 4.2% HSA is a suitable substitute for Dextran 40 as a reconstitution/washing medium for PBPC products.

Asunto(s)

RESUMEN

BACKGROUND: Babies with congenital hydrocephalus often experience developmental disabilities due to brain injury associated with prolonged increased pressure on the developing brain parenchyma. Umbilical cord blood (CB) infusion has favorable effects in animal models of brain hypoxia and stroke and is being investigated in clinical trials of brain injury in both children and adults. We sought to establish the safety and feasibility of repeated intravenous infusions of autologous CB in young babies with congenital hydrocephalus. METHODS: Infants with severe congenital hydrocephalus and an available qualified autologous CB unit traveled to Duke for evaluation and CB infusion. When possible, the CB unit was utilized for multiple infusions. Patient and CB data were obtained at the time of infusion and analyzed retrospectively. RESULTS: From October 2006 to August 2014, 76 patients with congenital hydrocephalus received 143 autologous CB infusions. Most babies received repeated doses, for a total of two (n = 45), three (n = 18), or four (n = 4) infusions. There were no infusion-related adverse events. As expected, all babies experienced developmental delays. CONCLUSION: Cryopreserved CB products may be effectively manipulated to provide multiple CB doses. Repeated intravenous infusion of autologous CB is safe and feasible in young babies with congenital hydrocephalus.

Asunto(s)

RESUMEN

BACKGROUND: Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment. METHODS: In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls. RESULTS: No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively. CONCLUSION: UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell-containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01221857. FUNDING: Gamida Cell Ltd.

Asunto(s)

RESUMEN

OBJECTIVE: To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. RESULTS: Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. CONCLUSIONS: Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.

Asunto(s)

RESUMEN

OBJECTIVES: To assess the elastic modulus (EM), volumetric shrinkage (VS), and polymerization shrinkage stress (PSS) of experimental highly filled nanohybrid composites as a function of matrix composition, filler distribution, and density. METHODS: One regular viscosity nanohybrid composite (Grandio, VOCO, Germany) and one flowable nanohybrid composite (Grandio Flow, VOCO) were tested as references along with six highly filled experimental nanohybrid composites (four Bis-GMA-based, one UDMA-based, and one Ormocer®-based). The experimental composites varied in filler size and density. EM values were obtained from the "three-point bending" load-displacement curve. VS was calculated with Archimedes' buoyancy principle. PSS was determined in 1-mm thick specimens placed between two (poly)methyl methacrylate rods (Ø=6mm) attached to an universal testing machine. Data were analyzed using oneway ANOVA, Tukey's test (α=0.05), and linear regression analyses. RESULTS: The flowable composite exhibited the highest VS and PSS but lowest EM. The PSS was significantly lower with Ormocer. The EM was significantly higher among experimental composites with highest filler levels. No significant differences were found between all other experimental composites regarding VS and PSS. Filler density and size did not influence EM, VS, or PSS. SIGNIFICANCE: Neither the filler configuration nor matrix composition in the investigated materials significantly influenced composite shrinkage and mechanical properties. The highest filled experimental composite seemed to increase EM by keeping VS and PSS low; however, matrix composition seemed to be the determinant factor for shrinkage and stress development. The Ormocer, with reduced PSS, deserves further investigation. Filler size and density did not influence the tested parameters.

Asunto(s)

RESUMEN

AIM: To compare the tensile bond strength (TBS) and adhesive remnant index (ARI) of three flowable resin-based composites and three orthodontic adhesive systems for metal bracket bonding. METHODS AND MATERIALS: Sixty bovine incisors were randomly divided into six groups. Enamel surfaces were etched with 37 percent phosphoric acid for 30 seconds and stainless steel orthodontic brackets were bonded using either flowable resin-based composites (3M Flow, FL; Tetric Flow, TF; and Wave, WA) or orthodontic bonding systems (Transbond XT, TX; Concise Orthodontic, CO; Fill Magic Ortodôntico, FM). All specimens were thermal cycled and stored in distilled water at 37°C for 24 hours, after which they were subsequently tested for TBS using a universal testing machine. ARI scores were determined after the failure of brackets. TBS and ARI data were submitted to ANOVA, Tukey, and Kruskal-Wallis tests (p=0.05), respectively. RESULTS: Rankings of the resin-based composites based on TBS means (MPa) were TX (6.4 ± 2.1), followed by CO (4.5 ± 2.7), FM (3.7 ± 1.2), FL (3.6 ± 1.2), TF (3.3 ± 1.2), and WA (2.4 ± 0.6). CO exhibited the lowest ARI mean score (0.9 ± 1.2) which was significantly different from the other five materials: TX (2.8 ± 0.42), FM (2.8 ± 0.42), FL (2.9 ± 0.32), TF (2.9 ± 0.32), and WA (3.0 ± 0.01). However, there were no statistically significant differences among the other groups with mean scores of 2.8-3.0. A score of 3.0 indicated that all the resin remained bonded to the tooth surface. CONCLUSION: The flowable resin-based composites tested (Fl, TF, and WA) used to bond metal orthodontic brackets to bovine enamel had low mean TBS values but acceptable ARI mean scores. CLINICAL SIGNIFICANCE: Flowable composites may not be appropriate for bracket bonding, unless the teeth to be bonded are not subjected to higher orthodontic stresses, such as those without an antagonist.

Asunto(s)

RESUMEN

OBJECTIVES: To verify the effect of interposing different indirect restorative materials on degree of conversion (DC), hardness, and flexural strength of a dual-cure resin cement. METHODS: Discs (2 mm-thick, n=5) of four indirect restorative materials were manufactured: a layered glass-ceramic (GC); a heat-pressed lithium disilicate-based glass-ceramic veneered with the layered glass-ceramic (LD); a micro-hybrid (MH); and a micro-filled (MF) indirect composite resin. The light transmittance of these materials was determined using a double-beam spectrophotometer with an integrating sphere. Bar-shaped specimens of a dual-cure resin cement (Nexus 2/SDS Kerr), with (dual-cure mode) and without the catalyst paste (light-cure mode), were photoactivated through the discs using either a quartz-tungsten-halogen (QTH) or a light-emitting diode (LED) unit. As a control, specimens were photoactivated without the interposed discs. Specimens were stored at 37 masculineC for 24h before being submitted to FT-Raman spectrometry (n=3), Knoop microhardness (n=6) and three-point bending (n=6) tests. Data were analyzed by ANOVA/Tukey's test (alpha=0.05). RESULTS: MH presented the highest transmittance. The DC was lower in light-cure mode than in dual-cure mode. All restorative materials reduced the cement microhardness in light-cure mode. GC and LD with QTH and GC with LED decreased the strength of the cement for both activation modes compared to the controls. Curing units did not affect DC or microhardness, except when the dual-cure cement was photoactivated through LD (LED>QTH). Flexural strength was higher with QTH compared to LED. CONCLUSIONS: Differences in transmittance among the restorative materials significantly influenced cement DC and flexural strength, regardless of the activation mode, as well as the microhardness of the resin cement tested in light-cure mode. Microhardness was not impaired by the interposed materials when the resin cement was used in dual-cure mode.

RESUMEN

BACKGROUND: A pilot study was conducted to determine the safety and feasibility of intravenous administration of autologous umbilical cord blood (CB) in young children with acquired neurologic disorders. Most CB units (CBUs) were electively stored in private CB banks. Unlike public banks, which utilize specific criteria and thresholds for banking, private banks generally store all collected CBUs. STUDY DESIGN AND METHODS: CBUs of eligible patients containing more than 1 × 107 cells/kg were shipped to Duke from the banks of origin after confirming identity by HLA typing. On the day of infusion, CBUs were thawed and washed in dextran-albumin and infused intravenously. Patients were medicated with acetaminophen, diphenhydramine, and methylprednisolone before transfusion. Data regarding patients, infusions, and CBUs were collected retrospectively. Characteristics of CBUs were compared to existing data from CBUs publicly banked at the Carolinas Cord Blood Bank. RESULTS: From March 2004 to December 2009, 184 children received 198 CB infusions. Three patients had infusion reactions, all responsive to medical therapy and stopping the infusion. Median precryopreservation volume (60 mL vs. 89 mL, p < 0.0001), total nucleated cell count (4.7 × 108 vs. 10.8 × 108, p < 0.0001), and CD34 count (1.8 × 106 vs. 3.0 × 106, p < 0.0001) were significantly lower than publicly stored CBUs. Postthaw sterility cultures were positive in 7.6% of infused CBUs. CONCLUSION: IV infusion of autologous CB is safe and feasible in young children with neurologic injuries. Quality parameters of privately banked CBUs are inferior to those stored in public banks. If efficacy of autologous CB is established clinically, the quality of autologous units should be held to the same standards as those stored in public banks.

Asunto(s)

RESUMEN

OBJECTIVE: To evaluate the biaxial and short-beam uniaxial strength tests applied to resin composites based upon their Weibull parameters, fractographic features and stress distribution. METHODS: Disk- (15 mm x 1 mm) and beam-shaped specimens (10 mm x 2 mm x 1 mm) of three commercial composites (Concept/Vigodent, CA; Heliomolar/Ivoclar-Vivadent, HE; Z250/3M ESPE, FZ) were prepared. After 48h dry storage at 37 degrees C, disks and beams were submitted to piston-on-three-balls (BI) and three-point bending (UNI) tests, respectively. Data were analyzed by Weibull statistics. Fractured surfaces were observed under stereomicroscope and scanning electron microscope. Maximum principal stress (sigma(1)) distribution was determined by finite element analysis (FEA). Maximum sigma(1-BI) and sigma(1-UNI) were compared to FZ strengths calculated by applying the average failure loads to the analytical equations (sigma(a-BI) and sigma(a-UNI)). RESULTS: For BI, characteristic strengths were: 169.9a (FZ), 122.4b (CA) and 104.8c (HE), and for UNI were: 160.3a (FZ), 98.2b (CA) and 91.6b (HE). Weibull moduli (m) were similar within the same test. CA and HE presented statistically higher m for BI. Surface pores (BI) and edge flaws (UNI) were the most frequent fracture origins. sigma(1-BI) was 14% lower than sigma(a-BI). sigma(1-UNI) was 43% higher than sigma(a-UNI). SIGNIFICANCE: Compared to the short-beam uniaxial test, the biaxial test detected more differences among composites and displayed less data scattering for two of the tested materials. Also, biaxial strength was closer to the material's strength estimated by FEA.

Asunto(s)

RESUMEN

Fat is often included in common foods as an emulsion of dispersed oil droplets to enhance the organoleptic quality and stability. The intragastric acid stability of emulsified fat may impact on gastric emptying, satiety and plasma lipid absorption. The aim of the present study was to investigate whether, compared with an acid-unstable emulsion, an acid-stable fat emulsion would empty from the stomach more slowly, cause more rapid plasma lipid absorption and cause greater satiety. Eleven healthy male volunteers received on two separate occasions 500 ml of 15 % (w/w) [13C]palmitate-enriched olive oil-in-water emulsion meals which were either stable or unstable in the acid gastric environment. MRI was used to measure gastric emptying and the intragastric oil fraction of the meals. Blood sampling was used to measure plasma lipids and visual analogue scales were used to assess satiety. The acid-unstable fat emulsion broke and rapidly layered in the stomach. Gastric emptying of meal volume was slower for the acid-stable fat emulsion (P < 0.0001; two-way ANOVA). The rate of energy delivery of fat from the stomach to the duodenum was not different up to t = 110 min. The acid-stable emulsion induced increased fullness (P < 0.05), decreased hunger (P < 0.0002), decreased appetite (P < 0.0001) and increased the concentration of palmitic acid tracer in the chylomicron fraction (P < 0.04). This shows that it is possible to delay gastric emptying and increase satiety by stabilising the intragastric distribution of fat emulsions against the gastric acid environment. This could have implications for the design of novel foods.

Asunto(s)

RESUMEN

AIMS: To audit our experience with gastrointestinal investigation of iron deficiency anemia (IDA) and assess whether gastric atrophy associates with and likely causes it. METHODS: This is a case-control study in a large U.K. teaching hospital. In total, 161 unselected patients undergoing routine investigation for iron deficiency anemia were submitted for the study, of which 5 were excluded for lack of appropriate biopsies. In total, 169 patients identified retrospectively from pathology records who had appropriate biopsies with a normal hemoglobin and no evidence of iron deficiency constituted the control group. In the group with anemia, a further internal case-control study compared cases where no definite cause for anemia was detected with controls who had a definite accepted cause for anemia. The gastric pathology, especially the presence and degree of body atrophy, was assessed by a single pathologist in both groups. Other factors including age, sex, and Helicobacter pylori infection were also evaluated. RESULTS: The mean age of the cases was 68 yr (95% confidence interval [CI] 34-102), and for the controls, it was 53 yr (95% CI 19-87). In the patients with anemia, 40 of 156 (25.6%) had significant body atrophy compared with just 7 of 169 (4.6%) of controls (P < 0.001). In a multivariate analysis, only significant body atrophy, odds ratio (OR) of 7.6 (3.1-18.6), and age, OR 1.048/yr (1.032-1.064), emerged as significant factors predicting anemia. In the cases, 35 of 156 (22%) patients had another definite cause of anemia. Of these, only 3 of 35 (9%) had significant atrophy, significantly less than the 37 of 121 (31%) without another definite cause (P = 0.008). In this anemic group, there was no difference in age between those with and without atrophy. CONCLUSIONS: Gastric atrophy is strongly associated with IDA, and this is likely to be causative in some patients and contributory in others. Gastric biopsies, especially from the corpus, may provide valuable information in the investigation of IDA.

Asunto(s)

RESUMEN

Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories.

Asunto(s)