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Experimental design showing study phases of best medical therapy and follow-up after transplantation of islets into patients with type 1 diabetes mellitus, including subsequent transplantations (when necessary). ACE indicates angiotensin-converting enzyme.
Postpurification yields. Shading indicates the increased yield after repurification.
Islet yield from consecutive isolations with secondary purification.
Daily glucose levels and insulin requirements in 10 patients who were able to stop insulin therapy after islet transplantation. To convert blood glucose to millimoles per liter, multiply by 0.0555. IE indicates islet equivalents; error bars, SE.
Posttransplantation C-peptide levels for 10 patients who received isolated islets. A, C-peptide level vs time in patients not receiving insulin during the entire study period. B, C-peptide level vs time in patients who returned to some insulin therapy during prolonged follow-up. To convert C-peptide to nanomoles per liter, multiply by 0.333.
Hemoglobin A1c (HbA1c) levels before and after islet transplantation. ANOVA indicates analysis of variance; error bars, SE.
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Warnock GL, Meloche RM, Thompson D, et al. Improved Human Pancreatic Islet Isolation for a Prospective Cohort Study of Islet Transplantation vs Best Medical Therapy in Type 1 Diabetes Mellitus. Arch Surg. 2005;140(8):735–744. doi:10.1001/archsurg.140.8.735
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Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005
A local multiorgan donor pancreas procurement program can provide a source for optimized isolation of purified viable islets for transplantation into patients with type 1 diabetes mellitus receiving best medical therapy.
Prospective before-after cohort study.
Tertiary referral center.
Glycemic control was assessed in 10 patients with diabetes-induced renal dysfunction who were enrolled in a best medical therapy program and then crossed over to islet transplantation.
Thirty human pancreata were retrieved from local multiorgan donors and consecutively processed with intraductal collagenase perfusion, continuous digestion, and density gradient purification (group 1, n = 9) or similarly processed but impure tissue fractions cultured in vitro and then repurified to retrieve additional islets (group 2, n = 21). Islets were implanted by percutaneous portal embolization, providing more than 10 000 islet equivalents (IE) per kilogram of body weight (infusions from 1-3 donors per patient) under cover of antithymocyte globulin, sirolimus, or mycophenolate mofetil and tacrolimus.
Main Outcome Measures
Islet yields, purity, and cell viability (caspase 3, terminal deoxynucleotidyl transferase–mediated biotin-deoxyuridine 5-triphosphate nick-end labeling stain, and insulin secretion in vitro) were compared. In patients, monitored metabolic parameters were C-peptide secretion, insulin requirements, glycemic excursion, and hemoglobin A1c (HbA1c).
For group 1 vs group 2, no differences were observed in pancreas age (43 vs 44 years), cold storage (5 vs 4 hours), or weight (73 vs 82 g). Group 2 yielded 453 690 IE vs 214 109 IE in group 1 (P = .002). Grafts contained 50% or more endocrine cells in both groups. No difference occurred in cell viability or insulin secretion. Islets from 90% of group 2 pancreata met release criteria for transplantation. C-peptide secretion was detected in all recipients and persisted with a median follow-up to 12 months (range, 6-21 months) after full islet transplantation. Daily insulin dependence was reversed in all patients for at least 3 months. Five patients resumed small insulin doses. Compared with the best care program, all patients had improved metabolic stability. The mean ± SE HbA1c level at entry into the study was 7.8% ± 0.5%, and this decreased to 6.9% ± 0.2% after best care (P = .38) and further to 6.2% ± 0.2% at 6 months after transplantation (P = .002 vs entry; P = .15 vs best care; analysis of variance).
Local pancreas donor retrieval with islet isolation and culture conditioning enabled an offer of islets for transplantation for 90% of consecutively processed pancreata. Isolated islets secreted insulin during prolonged follow-up after implantation into patients, yielding metabolic control comparable with that achieved by best medical therapy.
Interest has been renewed in human islet transplantation for type 1 diabetes mellitus. Recent progress with improved islet isolation, avoidance of glucocorticoid immunosuppression, and provision of adequate islet mass (>10 000 islet equivalents [IE] per kilogram of body weight) from multiple donors has yielded improved islet function in recipients with type 1 diabetes with hypoglycemic unawareness.1 Despite this advance, significant challenges remain to obtain sufficient islets. Where established whole-organ pancreas transplantation programs exist, significant numbers of pancreata do not qualify for whole-organ transplantation, and recent data suggest that these could be retrieved and subjected to islet isolation to expand a transplantation program for diabetes.2
We hypothesized that an effective program of islet transplantation could be established on the strengths of an existing pancreas procurement program that provides for whole-pancreas transplantation. This hypothesis is supported by studies that show that local organ donor procurement programs are the first strength in achieving good-quality human islet isolation.3 Local donation significantly reduces hypothermic cold storage time that elapses before the pancreas is subjected to islet isolation, thus optimizing the separation of islets from the exocrine and ductal cells of the pancreas.
According to several investigators, more promising success in islet transplantation has been observed in patients who received islet transplants alone.1,2,4 Many of these recipients had received conventional medical treatment for "brittle" diabetes or hypoglycemic unawareness. It is unknown if transplantation of islets alone may also be an attractive alternative for patients with type 1 diabetes who receive best medical therapy. Best medical therapy is defined as the control of blood glucose with intensive insulin therapy, blood lipids with statins, blood pressure with antihypertensive agents, and renal protection with angiotensin-converting enzyme (ACE) inhibitors. Despite these stringent measures for medical therapy, progressive microvascular complications from type 1 diabetes still occur. In this study, we report on the initiation of a novel protocol for human islet isolation from our local pancreas organ procurement program, in which islet isolation is optimized by repurifying impure tissue fractions saved during the initial pancreas processing. We also report on long-term glycemic control in a cohort of 10 patients who received pancreatic islet transplants after initial treatment in the best medical therapy program.
Specific aims of this research were to improve recovery of high-quality human pancreatic islets from individual pancreata and to compare the glycemic control in a cohort of patients with type 1 diabetes who received best medical therapy with their glycemic control after islet transplantation. The study was a prospective before-after cohort design in which all patients were initially enrolled in intensive medical therapy. Data in this study were collected for the initial 10 patients, who completed a minimum of 6 months in both programs. They are the first of a larger ongoing cohort of 50 patients to investigate effects on chronic complications. Inclusion criteria for recipients included a target population of men and women older than 20 years and younger than 60 years with type 1 diabetes confirmed by negative C-peptide levels (<0.222 ng/mL [<0.074 nmol/L]) for more than 5 years, who had elevated microalbuminurea, diabetic retinopathy, a creatinine clearance of more than 70 mL/min (1.17 mL/s), and signed informed consent. Exclusion criteria were body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 30, previous organ transplantation, active heart disease, planned pregnancy, active infection, malignancy, and lack of compliance. Sample size specification for the study was calculated based on a type I error of .05 and a type II error of .1 for equivalence testing. A consecutive sampling method was performed for the first patients who met inclusion and exclusion criteria. The study was approved by the research ethics board of the University of British Columbia, Vancouver, in March 2003.
Human pancreata were obtained (with consent) from adult heart-beating cadaver organ donors through the organ procurement program of the British Columbia Transplant Society, Vancouver. Thirty consecutive human pancreata were retrieved using an identical protocol to that for the whole-organ pancreas transplantation. This includes en bloc dissection with the "no-touch" technique and hypothermic in situ vascular perfusion with University of Wisconsin (UW) solution, with care being taken to avoid elevated portal pressure. Immediate surface cooling of the pancreas was achieved with 4°C ice slush in the lesser omental sac. Pancreata were transported at 4°C in sterile containers to the Ike Barber Human Islet Transplant Laboratory at Vancouver General Hospital, Vancouver, British Columbia.
Consecutive pancreata were subjected to islet isolation.3 The group 1 (n = 9) pancreata were processed with collagenase (Liberase HI; Roche Applied Science, Indianapolis, Ind) perfused via the ducts, continuous chamber digestion, and continuous density gradient purification using the Ficoll-Hypaque technique. Group 2 (n = 21) pancreata were similarly processed, but additional islets were retrieved by repurifying impure tissue fractions that remained after the initial purification. To accomplish this, the impure tissue fractions were subjected to in vitro culture at 22°C under conditions of 95% air and 5% carbon dioxide in 15-cm tissue culture plates that contained 35 mL of Connaught Medical Research Labs–based media (catalog No. 99-785-cv; MediaTech Inc, Herndon, Va). Cultures were maintained for 12 to 36 hours before the repurification protocol. In all instances, purified islets were subjected to in vitro culture for 12 to 36 hours before transplantation into humans.
Islet samples were collected in duplicate, counted, and sized for standard yields of islets equivalent to 150 μm.5 Samples were subjected to glucose challenge in vitro to detect insulin secretion, and results were expressed as a ratio of stimulated to basal insulin release.5 Islet quality control assessment included endotoxin assay by enzyme-linked immunosorbent assay, bacterial cultures, characterization of purity by cell composition,6 and detection of apoptosis by assay for caspase 3 activity (Cpp32 Fluorometric Assay Kit; BioVision Inc, Mountain View, Calif) and terminal deoxynucleotidyl transferase–mediated biotin-deoxyuridine 5-triphosphate nick-end labeling (TUNEL) stain (APO-BRDU Kit; BioSource International, Camarillo, Calif).
The indication for patient enrollment in this study was some degree of end-organ damage induced by type 1 diabetes, in particular, early evidence of renal dysfunction defined as elevated microalbuminurea (>300 mg of albumin in 24 hours). The aim was to provide some advantage to all patients with either best medical therapy or islet transplantation. Although hypoglycemic unawareness existed to some extent in 1 patient, this was not a criterion for enrollment in the present study. Persons who were entered into the study complied with protocols during a 3-month run-in period of participation in the University of British Columbia's best medical therapy program. Best medical therapy included intensive blood glucose management with insulin, blood pressure control, blood lipid control, and use of ACE inhibitors or angiotensin II receptor antagonists for renal protection. Glycemic control targets were met according to guidelines published by the Diabetes Control and Complications Trial7 and the clinical practice recommendation of the American Diabetes Association.8 Patients contacted study nurses twice monthly by telephone or fax for insulin dose adjustment. Blood pressure was treated to targets of less than 130/80 mm Hg to prevent progression of renal disease.8 Lipid levels were checked every 6 months and treated with statins to reduce predicted 10-year risk of coronary artery disease in diabetes.9 Elevated microalbuminurea was detected, and an ACE inhibitor (ramipril) was administered in doses up to 10 mg/d.10
Patients (5 men and 5 women; mean ± SD age, 44.1 ± 7.6 years; mean ± SD body mass index, 24.7 ± 1.8) participated for a mean ± SD of 15.4 ± 5.3 months in the best medical therapy program and then received islet transplantation (Figure 1). The first 2 patients received islets isolated from group 1 pancreata, whereas the subsequent 8 received islets isolated from group 2 pancreata. Patients were transferred to the interventional radiology suite. With the patients under local anesthesia with 1% lidocaine, a 4F catheter (Cook Diagnostic and Interventional Products, Bloomington, Ind) was advanced percutaneously into the liver with fluoroscopic cannulation of the main portal vein. Islets were infused under gravity from each donor while monitoring portal pressure. Catheters were withdrawn, and the hepatic puncture tracks were sealed with Gelfoam (Pharmacia & Upjohn, Kalamazoo, Mich). Patients were observed overnight and discharged home after a mean ± SD length of stay of 1.3 ± 0.6 days (range, 1-3 days). Total islet dose exceeding 10 000 IE/kg was provided by 21 total infusions, which necessitated 1 infusion in 2 patients, 3 infusions in 3 patients, and 2 infusions in 5 patients. The final islet dose that was achieved after completed infusions was 13 806 ± 561 IE/kg (n = 10). Immunosuppression consisted of antithymocyte globulin induction (1 mg/kg per day for 5 days) covered with 2 doses of glucocorticoids (125 mg intravenously), followed by introduction of sirolimus or mycophenolate mofetil (n = 2) and tacrolimus. Sirolimus (Rapamune; Wyeth-Ayerst Canada Inc, Markham, Ontario) was given orally to maintain trough blood levels at 5 to 10 ng/mL. Tacrolimus (Fujisawa Canada Inc, Markham, Ontario) was administered to maintain trough concentration in the blood at 5 to 10 ng/mL. For subsequent infusions of islets, the induction was with the interleukin 2 receptor blocker basiliximab (2 doses of 20 mg).
Patients monitored their glucose levels before and after transplantation using memory capillary glucose meters. The fluctuations of glucose concentrations in each patient were calculated as the mean of the differences in the major fluctuations in high and low glucose values during multiple 24-hour periods and expressed as the mean amplitude of glycemic excursions (MAGE).11 C-peptide levels and insulin requirements were compared during medical therapy and after transplantation. Hemoglobin A1c (HbA1c) concentration was assessed at entry to best care, 6 months before transplantation (while receiving best care), and 6 months after transplantation. Duration of follow-up from transplantation in this report was defined as the time since the full (>10 000 IE/kg) islet dose was delivered (12 ± 5 months; median, 12 months; range, 6-21 months). Intensive follow-up was provided by teams of nurses and physicians in the University of British Columbia Diabetes Best Care and Solid Organ Transplant clinical programs.
Data are presented as mean ± SE unless otherwise stated. Donor variables, islet yields, insulin secretion, and caspase 3 activity were compared with the t test for paired data. Patient follow-up data for blood glucose, insulin requirements, and HbA1c concentrations were compared using repeated-measures analysis of variance (ANOVA) with a Bonferroni adjustment of the stated level of statistical significance for multiple comparisons of 3 groups.
Table 1 gives the pancreatic donor age, cold storage time, and pancreas weight. There were no statistically significant differences between these 2 groups of donors. A comparison of purified islet yields from group 1 (n = 9) and group 2 (n = 21) pancreata is shown in Figure 2. A total of 214 109 ± 53 184 IE were obtained from the pancreata with single-stage purification, and this was not significantly different from the initial purification of the second group of pancreata, which yielded 333 885 ± 37 576 IE. The addition of a secondary purification significantly improved the overall yields for group 2 to 453 690 ± 48 145 IE (P = .002 vs group 1). Corresponding data in IE per gram of pancreas showed a yield of 2933 IE/g with single purification. The addition of secondary purification significantly increased overall yields to 5533 IE/g.
The concentration of endotoxin in isolated islet preparations was 0.14 ± 0.02 endotoxin units/mL, which was well below the acceptable range. No instance of microbiologic contamination was detected. Insulin release in vitro for the 2 groups of islets revealed a stimulation index of 2.7 ± 0.5 for group 1 vs 3.7 ± 0.8 for group 2 (P = .28). Cellular composition of the grafts is given in Table 2. The overall proportion of β-cells in group 1 was 35.8% ± 5.7% vs 31.1% ± 4.1% in group 2. A slightly greater proportion of cells bearing ductal (cytokeratin 19) and acinar phenotypes was observed in group 2. Islet cell caspase 3 activity (fluorometric units) as an index of apoptosis was 183 ± 35 in islets after initial purification, which remained unchanged after secondary purification from the same donors at 179 ± 33 (P = .93). The TUNEL staining of purified islets showed no difference between primary vs secondary purification.
Figure 3 shows islet yields from the consecutive series of 21 isolations performed with secondary purification. The data demonstrate that secondary purification augmented the islet yield in all of these 21 isolations. The threshold for islet yield to meet release criteria for transplantation was 250 000 IE. In 19 of the 21 isolations, this threshold was met or exceeded, and in 7 instances this threshold was enabled as a result of the secondary purification protocol. Thus, the overall offer of islets for transplantation was 90% of these consecutively processed pancreata.
Figure 4 summarizes mean 24-hour blood glucose levels and insulin doses during phases of best care, after initial islet transplantation, and after a full islet dose was transplanted. During best care, patients required 0.53 ± 0.6 U/kg per day of insulin. After the first transplantation, insulin doses decreased to 0.19 ± 0.06 U/kg per day (P<.001) and after full islet doses, all 10 patients stopped taking insulin completely. Glucose levels remained unchanged at 140.54 ± 0.54 mg/dL (7.8 ± 0.3 mmol/L), 142.34 ± 7.21 mg/dL (7.9 ± 0.4 mmol/L), and 136.94 ± 3.60 mg/dL (7.6 ± 0.2 mmol/L), respectively, during these 3 phases (P = .85, .57, and .43, respectively). Five patients (1 of the 2 who received group 1 islets and 4 of the 8 who received group 2 islets) have continued not to take insulin for 6 to 21 months; the other 5 returned to taking some insulin after further follow-up periods of 3 to 9 months (0.18 U/kg per day). Some of these latter patients preferred a lifestyle choice of enjoying a less restricted diet, for which they compensated by injecting insulin on some days.
C-peptide levels immediately rose from undetectable levels (<0.222 ng/mL [<0.074 nmol/L] in our assay) to levels of 0.601 to 2.40 ng/mL (0.2-0.8 nmol/L) after transplantation and remained persistently elevated during the follow-up of all 10 patients. Figure 5A demonstrates C-peptide concentrations throughout the follow-up period for all insulin-independent patients, and Figure 5B demonstrates corresponding levels for all patients who returned to some insulin therapy. There was sustained C-peptide secretion at similar levels in both of these groups whether or not they required insulin.
As an index of metabolic lability, the mean amplitude of glycemic excursion scores was calculated, demonstrating values of 7.8 ± 0.5 for best medical care and improving to 3.5 ± 1.3 for the transplantation phase (P<.001; paired t test). This improved stability was reflected by the observation that no patient has had problems of hypoglycemia since the transplantation.
Assessment of HbA1c levels is demonstrated in Figure 6. Comparison of HbA1c concentrations before best care (7.8% ± 0.5%), during best care (6.9% ± 0.2%), and 6 months after islet transplantation (6.2% ± 0.2%) shows significant reduction in HbA1c levels. Islet transplantation achieved the best results compared with entry into the study (P = .002; ANOVA), but results between best care and transplantation were similar (P = .15; ANOVA).
Thirty-eight percent of the 21 infusions were followed by minor degrees of abdominal pain and 15% by nausea. After 3 islet infusions (2 initial and 1 second), postprocedure fluid was detected on ultrasonography, accompanied by a decrease in hemoglobin consistent with bleeding. No blood transfusions and no intervention were required. One of these patients had been receiving acetylsalicylic acid, which was withdrawn until he showed no further decrease in hemoglobin level. For all infusions, portal pressures before infusion were 11.7 ± 3.2 mm Hg, and this increased to 14.0 ± 2.4 mm Hg after infusion (P = .005; paired t test).
All patients who received islet infusions had immunosuppression-related adverse effects of mouth ulceration (n = 10) and neutropenia (n = 10). For these patients, the mouth ulcers responded to decreased doses or discontinuation (n = 2) of sirolimus therapy with conversion to mycophenolate mofetil. These patients retained stable islet function.
The modification to the islet isolation protocol in the current study appears promising. The culture-conditioning protocol added significant islet yields without compromising islet viability. Although the primary purification protocol tended to have higher yields in the group 2 pancreata processed, this did not appear to be due to differences in the donor characteristics. To exclude the possibility of a type II error, accounting for the (insignificant) trend to higher yields in group 2, we examined the prepurification yields and identified no differences in this parameter, suggesting that similar numbers of islets were available for purification in both groups. This tends to agree with the group 2 data, which demonstrate an augment of approximately 30% of islet yields when repurification is performed after culture conditioning.
The ability to offer more than 90% of isolated islet grafts agrees with earlier published data that a local retrieval program with short cold storage time is an effective program for providing islets for transplantation. The current data compare favorably with earlier published observations on rates for islets provided from successful isolations that have been reported as less than 50%.12 These data should encourage local donor programs to apply these protocols to offer islets for clinical islet transplant programs.
Despite the improvements in islet isolation demonstrated in these studies, patients continued to require large doses of islets. This high islet mass requirement exceeded published data of earlier studies13 and did not appear to be completely mitigated by glucocorticoid-free protocols. Contributing factors may be related to adverse effects of immunosuppressive drugs on islet engraftment,14 and more recent data suggest that prothrombotic activity in the portal venous system has an adverse effect on early islet engraftment.15 One of our recipients had detectable portal vein thrombosis on ultrasonography. He had initial insulin independence, but a delayed need for intermittent insulin was observed after 7 months.
Several investigators have recently reported experience with islet transplantation. Following a report of improved success with the Edmonton protocol in 2000,1 additional promising reports of islet transplant alone appeared from several centers.2,4,16 A multicenter trial of pancreatic islet transplantation in patients who followed the Edmonton protocol has been organized via the Immune Tolerance Network, which suggests success at experienced centers but less success in others, and the final data are still pending.17Critical analysis of the data from these studies reveals that significant improvement in the rate of insulin independence after isolated pancreatic islet transplantation is attributable to improved islet isolation, glucocorticoid-free immunosuppression, a transplant mass of more than 10 000 IE/kg, and selection of patients with brittle diabetes who have low body mass.
Longer-term follow-up suggests that the initial rate of insulin independence decreases after several months, particularly after the first year. Initial deterioration of function was observed in patients who followed the Edmonton protocol.18 In a more recent report19 of 11 transplant recipients with complete long-term data more than 1 year after transplantation, 6 resumed insulin therapy more than 12 months after transplantation. Similar observations have been made by other groups.2,4,20 In the current study, the islets have also been susceptible to reduced function with time, with patients returning to insulin therapy despite ongoing insulin secretion. The duration of graft follow-up was based on time elapsed after the full dose of islets was administered, which may account for the apparent difference in success rates of insulin independence, since the earlier reports of follow-up began with the first transplantation.
The reasons for delayed decline of function are unclear but may include adverse effects of immunosuppressive drugs on islet function. In the current study, we used antithymocyte globulin, which can induce islet toxicity from cytokine release. We also used a brief dose of corticosteroids to counteract the unpleasant cytokine release effects (fever and myalgia). Both of these agents represent a departure from the protocol reported by Edmonton.1 Delayed deterioration of an initially marginally engrafted islet mass may be due to an inhospitable intraportal transplantation site. Data from a large preclinical animal model previously characterized delayed failure of pure intraportal autologous islets, which was not observed in the splenic site.21
Results from the current study compare favorably with collective data recently reported by other investigators.2,4,20 In a poster report at the 20th International Transplantation Society Congress, September 5-10, 2004, the Collaborative Islet Transplant Registry identified insulin independence in 57.9% of recipients 12 months after their last infusion (B. J. Hering, MD, oral communication, September 6, 2004; www.citregistry.org.. The current study contrasts with the earlier studies, since recipients had higher body masses and hypoglycemic unawareness was not a sole indication for transplantation. Longer follow-up will be necessary to determine if this therapy can reduce nephropathy, retinal damage, and endothelial dysfunction better than medical therapy alone. A critical analysis of the glucose values in the current study shows improved glycemic excursions, but HbA1c remains marginally high at 6.2%, suggesting that caution must be taken to conclude that islet transplantation will prevent microvascular complications on the basis of improved glycemic control alone.
In summary, a strategy for culture conditioning of isolated pancreatic tissue obtained in a local organ donor program provides improved quantities of islets to support clinical islet transplantation. The current study demonstrates that these islets function for prolonged periods after intraportal transplantation into recipients with type 1 diabetes who entered a best medical therapy program, including insulin independence. The long-term follow-up data of the recipients demonstrate that some patients resume insulin therapy despite insulin secretion, a challenge reported by other groups. These data stress the need to redouble efforts to identify factors that may induce and sustain long-term islet function so that this therapy can be evaluated to prevent the long-term complications of diabetes.
Correspondence: Garth L. Warnock, MD, Department of Surgery, British Columbia Islet Transplant Centre, University of British Columbia, Suite 3100, 950 W 10th Ave, Vancouver, British Columbia, Canada V5Z 4E3 (email@example.com).
Accepted for Publication: February 28, 2005.
Funding/Support: Funding was provided by the British Columbia Transplant Society, the Vancouver Coastal Health Research Institute, the Canadian Foundation for Innovation, the Ike Barber Diabetes Research Endowment, and the PA Woodward Foundation. We thank Gregory Korbutt, PhD, at the University of Alberta, Edmonton, who performed graft cell composition and insulin secretion studies. We are grateful to Maria Lopes-Chau, Ingrid Ahlsten, and Lesley Miller for manuscript preparation.
Previous Presentation: This paper was presented at the 76th Annual Meeting of the Pacific Coast Surgical Association; February 19, 2005; Dana Point, Calif; and is published after peer review and revision. The discussions that follow this article are based on the originally submitted manuscript and not the revised manuscript.
Susan Orloff, MD, Portland, Ore: Thank you for the privilege of opening this discussion of another fine manuscript written by my colleague, Dr Garth Warnock, and his coworkers, as you know, describing the results comparing islet transplantation using multiorgan donors, either with standard collagenase perfusion or the standard perfusion technique plus repurification of impure tissue fractions cultured in vitro. They looked at islet yield, purity, cell viability, insulin secretion, and success of either method of islet isolation and transplantation compared to best medical therapy.
The incidence of diabetes is predicted to increase significantly in the next decade. It already affects 130 million people worldwide. Despite the efficacy of insulin therapy, the devastating secondary complications, including retinopathy, nephropathy, cardiovascular disease, and neuropathy, can shorten the life expectancy by as much as one third. Even though it has been demonstrated by the Diabetes Control and Complications Trial that tight control of blood glucoses with intensive insulin therapy significantly lowers the level of glycosylated hemoglobin and minimizes the progression of secondary complications, it does not abrogate these complications, and it also results in a significantly higher risk of the complications of severe hypoglycemic reaction, including seizure and coma.
These data underscore the importance of developing better treatment strategies, such as islet transplantation. The concept of transplanting extracts of pancreas in patients with diabetes is over a century old, with the first known report occurring in 1894. In the 1980s, reports of successful allogenic islet cell transplantation in patients with type 1 diabetes with the use of conventional immunosuppression and purified human islets from deceased donors began to appear. But internationally, the overall rates of success were reported to be less than 10%.
In 2000 Shapiro and his colleagues, including Dr Warnock, in Edmonton reported 100% success in 7 patients with modification of the immunosuppressive regimen and multiple infusions of islets from different donors to achieve normal glucose levels and independence from exogenous insulin. However, Edmonton's success has been tough to duplicate elsewhere.
Today we heard from Dr Warnock some very promising results, and I commend you and your colleagues on your efforts and success. However, we will anxiously await your longer-term follow-up of your patients as the current study goes out only 6 to 21 months posttransplantation of the full greater than 10 000–islet equivalents–per-kilogram dose.
I have a few questions. There are a number of successful islet transplant centers, including Minnesota, Miami, and I believe your former institution, Edmonton, that use the perfluorocarbon-based 2-layer method of cold storage to minimize the effect of cold ischemia, and they report an increased islet yield and functional success over static UW preservation. This method has also enabled expansion from the donor pool to include longer ischemia times greater than 10 hours, marginalized pancreata from non–heart-beating donors, and pancreata from older aged donors. You used the static UW solution for transport of your pancreata to the isolation laboratory, and I am wondering if you can comment on why you don't use the perfluorocarbon-based 2-layer method.
In your exclusion criteria, you exclude patients with cardiovascular disease, and you mentioned active heart disease. How is this defined? Do you exclude patients who have had a recent or remote coronary bypass graft and have no symptoms, or are these patients included as possible candidates for islet cell transplantation?
The experience with islet autotransplantation after total pancreatectomy suggests that if ischemia and immune reactivity could be circumvented, fewer islets are required to induce and maintain normoglycemia. You report on 2 patients who only required 1 infusion to reach the dose exceeding 10 000 islet equivalents per kilogram. Did you note any difference in characteristics of the donors, the pancreata, the procurement procedures, or the cold ischemic times in these 2 patients? In addition, you showed total yield on one of your grafts of 214 million IE in the first purification in group 1 who undergo the standard islet cell processing and in group 2 who undergo 2 purifications. In the first purification, the yield is about 334 million IE. Although this is not statistically significant, it does appear to represent a fairly large difference, and I am wondering how you can account for the differences in islet yield.
In the patients who required more than 1 islet infusion to reach the greater than 10 000 islet equivalents per kilogram, did the timing of the next infusion affect the outcome in terms of insulin independence? Also, other than perhaps differences in diet, what was unique to those 5 patients who required some insulin at 3- to 9-months follow-up after islet cell transplantation? You did show that there were sustained C-peptide secretions at similar levels in the group that did not require insulin compared to the group that did, but at a glance it looks like the levels were lower in the group that required insulin. Have you looked at titers of islet cell antigens and glutamic acid decarboxylase (GAD) antibodies in these patients, suggesting recurrence of the autoimmune response?
In your current protocol, which I actually didn't see in your slide presentation but in the manuscript, you mentioned that there is a minor departure from the Edmonton protocol where you give 2 doses of glucocorticoid, 125 mg. Albeit this is a very small exposure, I am wondering if this has a negative impact on the islets.
Can you comment on whether you think that the intrahepatic site is the best site for islet infusion given the 10% incidence of hepatic bleeding due to the procedure reported in the literature in addition to the high exposure of islets to toxins, including immunosuppressive medications that enter the portal vein, and the rare risk of portal vein thrombosis? Given that the alternative sites, such as omentum or peritoneal cavity, would avoid these issues, in addition, they would require overall less islet mass by avoiding the roughly 50% loss of islets during the purification process. What are your thoughts?
Finally, in this era of organ shortage, there is a significant motivation to search for new sources of transplantable islets. What are your thoughts about the potential for adult and embryonic pluripotent adult and embryonic stem cells, which are expandable in culture and have a potential to give rise to all cell types in the body, including islets, to be used as islet replacement tissue with the possibility of unlimited quantities to be generated? I am only aware of this in in vitro studies as well as in mice.
This paper is another very important contribution by Dr Warnock and his colleagues to the evolution of a treatment strategy that has the potential to improve the lives of a vast number of patients and represents the efforts of a highly focused and skilled team. This group undoubtedly has been the leading contributor to this goal, and I want to thank you for sharing your excellent results with us.
William H. Marks, MD, Seattle, Wash: I just want to dovetail a question to Dr Orloff's. When you look at the 5 recipients who returned to insulin therapy vs those who remained insulin free, did you find there was a difference in the percentage of the rescued islets that they received? Also, in your response, Dr Orloff, you referred to the culture being central to an effective isolation mechanism. Other groups have also identified a culture step as being an important part of obtaining viable islets. I wonder if you would briefly comment on what you believe to be the survival advantage derived by islets from the culture process.
Nancy L. Ascher, MD, PHD, San Francisco, Calif: I was wondering how your group goes about distributing islets vs solid-organ pancreas transplants. I think the audience may not be aware that, in fact, patients who would be candidates for solid-organ transplants are actually competing with those patients who could be candidates for islets. I was wondering how your group makes that distinction.
In addition, as we think about islet transplant outcome vs best practice, I wonder if you don't need a third group to compare and that is the patients who undergo solid-organ transplantations.
Dr Warnock: Thank you very much, Dr Orloff, and thanks to the other discussants for your very thoughtful comments. Dr Orloff, that was a very thoughtful review of some of the aspects of islet transplantation that I think helps us to really understand this area much more thoroughly. I will take your comments and questions in order.
You have asked us about comparison with the groups who are using a perfluorochemical, 2-layer pancreas storage. We didn't embark upon this at the time this study started, since the data were just beginning to emerge from the research at that time. Since our short cold storage time here is 4 to 5 hours, our laboratory team is available on call, the retrievals come from within the province, and the pancreas gets delivered to the laboratory right away, we didn't believe that we needed to really set this up. However, I agree with your comment that if one wants to optimize the situation where the logistics of transport require storage for over 8 hours, the data seem to suggest that perfluorochemical, 2-layer storage would be helpful.
You asked about exclusion of patients with active heart disease: this is defined as those persons with symptomatic angina pectoris who have positive MIBI [technetium Tc 99m sestamibi] scanning and certainly when they enter the best medical therapy program, they do receive clinical and MIBI screening, and if medical care can be optimized or stabilized with intervention or coronary artery bypass grafting, then they can become candidates for islet transplants.
You asked about the situation where 2 patients only required a single infusion, and we have indeed had a positive experience of being able to offer single-donor islets. I think that when we look at the dose of islets, one has to keep in mind that many programs select individuals for very lean body mass. They may get a lower islet dose, but it allows them to offer the critical islet mass much more effectively. We don't do that because these individuals have come forward through a screened best medical program and so we take all comers, providing the body mass index is not over 30.
In terms of the question you had about some differences you observed in the number of islets in group 1 and group 2 with a solitary purification, it's a good point. There can be differences in collagenase lots, even though investigators have seen more promising uniformity of lots, reducing variability. There was a shift in the collagenase used at that time. But to address this, we have looked at the prepurification islet yields and certainly didn't see any difference there, so I think our data really do reflect the augmented improvement from the repurification as demonstrated with the consecutive series processed with repurification.
In terms of the patients who had more than one infusion, to get more than 10 000 per kilogram body weight, we have not observed the increment of C-peptide secretion after multiple infusions that was expected. So there is no question in our minds that if you can do this right and get the right dose in there the first time, much the better. I think any step to go to single-donor infusion or even multidonor infusion at one time at the very first time point is the best objective.
You have asked us about those individuals who had returned back to some insulin therapy and whether that might be due to recurrent autoimmunity. Unfortunately, we don't have a way of tracking immune injury. The hopes and expectations that anti-GAD antibodies might discern autoimmunity haven't been proved due to lack of specificity: antibodies can increase whether patients are on insulin or not. Other criteria that our laboratory is evaluating are expression of tolerogenicity or microarray analysis in serum, and this might allow us to distinguish those subsets of individuals who have auto- or alloimmune-mediated vs tolerogenic response.
One of your questions was why some doses of steroids were given. We went to the T-cell–depleting regimen here, in contrast with the Edmonton protocol, to minimize any immune islet injury. These patients actually get quite an uncomfortable response to the antithymocyte globulin (ATG), and we felt the steroids gave them very good symptomatic relief of that. It is possible that those small doses may have had an effect, but in argument with that, some who have had the best long-term function had steroids. To minimize this, now we like to pretreat the recipients before the islet infusion goes in, providing the ATG along with a small dose of steroids before the infusion.
You have wondered if the intrahepatic site is best for islet infusion. It has allowed our radiology interventionalists to come in and do this on an elective basis because of a culture period rather than calling them in at night. But the intraportal site may not be optimal. When you look at preclinical studies in outbred animals, it's very clear that islets in the intraportal site show decline with time in function, and we don't see that in the intrasplenic site. Similarly, the omental pouch works, but unfortunately the islet doses are still quite high.
As far as the growth and development of islets, undoubtedly there is in the pancreas a stem cell, and in some of our preparations there are ductal elements that go in with the graft. Our analysis cannot yet discern if that might be a subset where there is better long-term function, but suffice to say it is extremely controversial in the basic biology literature as to what constitutes a pancreatic stem cell in adult pancreas. We have been very interested in having a developmental biologist work with us to look at the potential that a duct cell in the pancreas with these islets can contribute to better long-term function.
Dr Marks had asked us about the 5 patients who returned to insulin. Was there a difference in the outcome of these because of rescued islets? No, there were no differences in the rescued islets in those groups, but, as I have mentioned, the augment of C-peptide with the additional infusion was not what we expected it to be. What we surmise in that group is that perhaps a reinfusion into the portal circulation might increase the thrombogenic response with that augmented graft, and in fact there are data now to suggest that.
You have also wondered if culture affects the survival. Certainly, looking at insulin secretion and caspase apoptotic expression in the grafts, it seems that short-term culture does not adversely affect viability. There is a reduced islet number, but that's because the islets do shrink up after culture, and by our standard islet count protocols, would appear to be a reduction in islet mass.
Finally, Dr Ascher has asked us how we allocate organs where there may be a solid-organ or whole-organ pancreas program vs an islet program. Our program does offer whole-organ pancreas transplants to those individuals who have gone on to end-stage diabetic nephropathy, needing a kidney transplant. Those individuals are waitlisted and enter that program. This current study I have shown you is part of an ongoing 50-patient cohort study of patients who have entered best medical therapy with the aim of determining if we can prevent renal failure with a primary outcome of renal function. So there are 2 very separate groups. The 2 programs are complementary, not in competition, which agrees with previous data from the Philadelphia group. Whole-organ transplantation might well be an area that could be a third arm of such a study. I think that at this stage, with the immunosuppressive regimens, the use of calcineurin inhibitors, it makes it very difficult to get those patients into such a treatment protocol because one does need obligate use of those agents at bigger doses and that may adversely affect renal function. So certainly I think in the future, if our immunosuppression would be friendlier, it could be an excellent third arm.


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Some makes and models of trucks are less common or do not usually use camper shells, so there is a higher demand for camper shells that fit them. This drives up the price of used camper shells for those models.Continue Reading
Some trucks also come in varying bed lengths, so truck caps for extended beds may also drive up the price. Newer trucks also sometimes have curved or tapered rails, which require a more complex mold to fit them properly. Older or less expensive caps may not fit them tightly. Even trucks made by the same manufacturer vary significantly between models and have to have unique truck caps for a good fit. Some makes and models of trucks have had essentially the same bed for decades, so buying a used camper shell for them is easier and less expensive due to greater supply.
It may be difficult to find caps that fit less popular types of trucks at all, so the owner may have to buy a new or refurbished shell. If the buyer does find a used one, it often has to be repainted to match the truck. This is still usually cheaper than buying a new cap, however.
It can also be difficult to find a used shell that fits an older truck and does not block the top brake light, but this is mostly a problem in trucks and shells manufactured prior to 1995.Learn more about Vehicles

subset: commoncrawl


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OK, I know you've all been waiting with baited breath to hear (and see pictures) of baby Jacob. Well, he finally made his arrival just this morning at 6:01 AM ... weighing in at 9.56 lbs, 21-1/2 inches long, lots of dark hair and a very rosy complection. The perfect picture of a delicious baby if ever I've seen one! Oh, I did mention pictures, but you'll have to wait with that baited breath just a few more days cuuuzzzzz I don't get hooked up to the Internet until next Monday or Tuesday afternoon. Mommy and Daddy are doing fine, but a wee bit exhausted. Poor Mommy started labor late Tuesday night, arrived at the hospital Wednesday afternoon, and delivered the little fellow Thursday morning (today). She's a bit wiped out from the experience, and will spend the night with baby at the hospital. I tried to stay with her until Jacob was born, but alas, I had to scoot home to catch 1-1/2 hrs sleep and get Nathan on the bus at 7 this morning.
So, just put up with my library visits a bit longer (sorry no pics yet) ... life has been very exciting the past few days, weeks, and year! I'll try to visit your blogs ... I have about 20 minutes on my timer :)!
Thursday, March 29, 2007
Tuesday, March 20, 2007
I'm Here!
Just popped over to the library to use the computer; first time in nearly two weeks. We have just one phone line installed (temp.) ... no TV, and no Internet service. I must admit, it is rather nice not having all of the distractions of the modern world ... but I SO DO MISS ALL OF YOU! I'm still checking about the satellite Internet setup ... even if it costs more, it would be worth it. Elizabeth is due to have baby Jacob in seven more days! DH just got dropped off at the airport today, and Nathan is away for nearly 8 hrs a day at school (including the bus rides). Maybe next week I can be a lady of leisure for a bit. Well, I've got to run home and take a quick nap before the little fellow comes home from school.
Posted by Mrs. Mac at 4:54 PM 21 comments: Links to this post
Friday, March 09, 2007
I'm So "Dial-Up"
S L O W will soon be my middle or first name. I just found out that our new rural home is in an area not serviced by high speed Internet service. Here's hoping that my satellite TV connection has a faster mode of transportation ... otherwise it will be like stepping back in the dark ages of computer use for me.
We got the official OK with the county to move in today! So as soon as I unplug my computer, I may not have service again for the next week unless I visit my local library. I guess this comes with living in the country, a slower paced life, slower speed limits, and more time to smell the roses!
Posted by Mrs. Mac at 6:44 PM 15 comments: Links to this post
Labels: this and that
Wednesday, March 07, 2007
Preoccupied/Hot Flashs/Calgon Moment Needed
The post title explains my absence. I've been a damsel in distress but not willing to put up a white flag to surrender (not me). Of course two nights ago I had such bad heartburn I thought for a moment it was a heart attack; but two tums and an hour later, I was just fine. The very last item to tote over to the new home will be my bubble bath ... I just can't afford to misplace it for even a night. Leave me a kind note of encouragement to hang in there ... and I'll be back to posting after the move and the dust settles.
Photos: Guest room complete with doors and carpet, one of two stairways, master bathtub (needs to be repositioned and have the plumbing installed). More photos at "This New House" ... go ahead and visit ... just to the right in the sidebar
Posted by Mrs. Mac at 10:26 PM 10 comments: Links to this post
Labels: change of life, work around the house
Friday, March 02, 2007
Gearing Up For The Frenzy
Next Friday we should get the keys to our new home. It will be almost exactly 18 months since we first bought our land, designed our home, and waited patiently for all the plans to come together. Needless to say, the coming days will bring on a frenzy of activity (even more than that of our daughter's wedding last year). So much to remember ... transferring and cancelling utility services, changing schools (for Nathan) and an array of mind boggling STUFF TO DO! I have yet to start packing up our rental home ... and sooooo need to reserve a U-Haul truck. Still praying that our driveway will be snow and ice free so our PODS storage units can be delivered. Guess I'd better start making a To Do List! Please help me remember what I'm forgetting!
Posted by Mrs. Mac at 11:40 AM 9 comments: Links to this post
Labels: work around the house
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Below are pictures of some of the student-project teams in 1996. Unfortunately, I don't have pictures of all the fine projects that were done.
This team studied the effects of different liquids on the germination and growth of bean seedlings.
What effect does road salt have on grass? This team's work found the concentration of salt that would kill the grass or stunt its growth.
A student team with their plants on the misting bench in the rooftop greenhouse. They exposed plants to varying concentrations of UV light, trying to understand a little about the possible effects of ozone layer depletion. Mrika Robinson was one of their team members, not a plant they were studying!
Many of the student groups chose to study environmental impacts on plants. Many find this ethically more sound than similar experiments on animals. Students doing research projects in Biology 102 have access to virtually all of the Biology Department resources, including access to the rooftop greenhouse and its automated misting bench, pictured above.
Return to Biology 102 Main Page
Modified 11/22/96


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text: |Hani K Kaldass The apeNEXT project This paper presents the apeNEXT machine to the lattice quantum chromodynamice (LQCD) community. apeNEXT, like the other APE projects, is a three-dimensional torus of chips. Each chip contains a 64-bit arithmetic unit. Furthermore, each contains 7 bi-directional communication links: 6 links are used for nearest neighbour communication on the torus, while the 7-th link is used for high speed I/O communications with a front-end PC via a PCI board. Each chip is endowed with its own DDR memory. The apeNEXT board has 16 nodes. The paper discusses the apeNEXT software and compilation chain. The coding languages for apeNEXT are TAO and C language. Optimization takes place at the assembly code level by a software called ``sofan'' and instruction scheduling takes place by a software called ``shaker''. Benchmarks result are reported: Application of the Wilson-Dirac operator on a spinor leads to a sustained performance of 55%, while with the product of two SU(3) matrices, the efficiency goes as high as 65%.


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This information is provided for your convenience and may no longer be valid.
Know more about this business than we do? Cool! Please submit any corrections or missing details you may have.Help us make it right
Be the first SILive.com user to add photos or videos of Class Air Decorators
Class Air Decorators Llc is located at 681 Lawlins Rd Unit 80 in Wyckoff and has been in the business of Party Supplies Rental Services since 1983.
Class Air Decorators can be found at Lawlins Rd 681. The following is offered: Event Planners. The entry is present with us since Sep 9, 2010 and was last updated on Nov 14, 2013. In Wyckoff there are 2 other Event Planners. An overview can be found here.


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Via University Portal
Admin, Alumni, Guests
Are you an external organisation with an interest in reaching our students on campus? Below you will find all the information you need to know about LSESU Promotional Spaces within the Saw Swee Hock Student Centre.
For further information on prices and booking these spaces, please visit our Advertise with Us page.
Please note these are not society stall bookings - these can be booked through the LSESU ARC: email@example.com
The Pavilion is the space directly outside the Saw Swee Hock Student Centre, underneath the glass canopy.
You can request:
Bookings in this space must remain under the glass canopy as Sheffield Street is a public road owned by Westminster Council. Therefore, no music can be played in this area and any bookings in this area must keep noise levels to a minimum – unless a licence has been secured from Westminster Council.
While remaining under the glass canopy, every measure must be taken to ensure that no doors or walkways in or out of the Saw Swee Hock Student Centre are blocked as they are fire escapes.
This promotional space is situated directly next to the LSESU Denning Learning Café and has a high footfall of students passing through to the Activities Resource Centre, the café and the upper and lower floors of the building.
Because of its location, no food-related promotions are allowed to take place, although food can be bought from the café and given away for free – this must be pre-arranged with the LSESU Events Team.
This space includes a table with 10 chairs, which can be removed if requested.
There is a curtain which can be drawn around the space, closing it off from the café and making the space appropriate for meetings / study space. Please note: this does not make it entirely private and noise will travel to and from the café.
London School of Economics & Political Sciences Students' Union.
Charity Number (Registered Charity: Charity Commission): 1143103; Company Number (Company Limited by Guarantee): 7710669; We are a London Living Wage employer.
Site powered by Membership Solutions.


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Milani Bella Eyes Gel Powder Eyeshadow
BY MILANI #93 in Eyeshadow
Product Description
Bella Eyes Gel Powder Eyeshadow glides on in a single stroke, delivering a multidimensional finish. The formula starts as a gel and transforms into a stunning powder eyeshadow once applied. Use dry for a beautiful wash of color or wet for a more vivid look.
Mica, Synthetic Fluorphlogopite, Silica, Aluminum Starch Octenylsuccinate, HDI/Trimethylol Hexyllactone Crosspolymer, Dimethicone, Isononyl Isononanoate, VP/Hexadecene Copolymer, Cetyl PEG/PPG-10/1 Dimethicone, Octyldodecanol, Magnesium Aluminum Silicate, Nylon-12, Caprylyl Glycol, Ethylhexylglycerin, Ammonium Acryloyldimethyltaurate/Beheneth-25 Methacrylate Crosspolymer, Polysorbate 20, Polyisoprene, Talc, Pentaerythrityl Tetra-di-t-Butyl Hydroxyhydrocinnamate.
+/- May Contain: Tin Oxide, Titanium Dioxide (CI 77891), Iron Oxides (CI 77491, CI 77492, CI 77499), Manganese Violet (CI 77742), Ultramarines (CI 77007), Ferric Ferrocyanide (CI 77510), Carmine (CI 75470).
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Play with Heavy Machinery
E-Voucher Delivery
Print or Email Instantly! You can also choose your send date.
When do I choose a date?
If giving as a gift, your recipient can choose a date at their convenience; otherwise, you can choose one after checkout.
Hassle-Free Policies
30 day returns. Free exchanges. No expiration dates.
Wednesday through Saturday - daylight hours
Let your inner child discover what it would be like to work on a construction site and Play with Heavy Machinery!
- Work your way through activities and obstacles based on your selected piece of equipment
- Featured on Shark Tank and named a top attraction in Minneapolis/St. Paul by TripAdvisor
- Experience takes place at the first and only recreational heavy equipment adventure playground in the Midwest
- No experience necessary, only the desire to have an amazing time!
Climb behind the controls of heavy equipment and into an adult-sized sandbox where you can dig, doze, or dump to your heart's content!Key Info>
At the time of booking you will select one piece of equipment to control during your experience: Excavator, Bulldozer, or Wheel Loader.
Your adventure begins with a short safety training program and equipment overview. After being fitted with hands-free radio communication between you and your instructor, you are ready take the controls!
Your experience takes place on an undeveloped "jobsite", where you will test your hand eye coordination and skill. Your activities and obstacles will depend on the type of machinery selected.
It feels just like a real construction site, only more fun!
Classic Sandbox for 1 Participant:
At the time of booking you will choose one piece of equipment to control during your experience: Excavator, Bulldozer, or Wheel Loader.
Classic Sandbox for 2 Participants:
Select our option for 2 participants if you would like to split your experience time with a friend.
Essential Information
- No experience necessary
- Participants must be at least 14 years of age.
- Minors must be accompanied by a parent or legal guardian
- Children are not allowed near the equipment, but are encouraged to come and watch from the spectator viewing area during the experience. Children are also invited to sit in the equipment when it is parked and not running.
Duration1.5 hours with 30 minutes of instruction, followed by 60 minutes of equipment use
Maximum ParticipantsThe equipment is single rider only.
SpectatorsSpectators are welcome to come watch from a comfortable viewing area that overlooks the sandbox.
Weather DependentThis experience runs rain or shine. Your experience provider will do their best to call you prior to your session to reschedule in the case of extreme weather. Always contact the Experience provider with any questions regarding weather conditions.
What To WearAll equipment has climate controlled enclosed cabs that can be adjusted for comfort. Be sure to wear comfortable and durable clothing; jeans are recommended. You will likely get dirty, so don't wear your favorite clothes! Close-toed shoes are required.
Booking InformationFor this experience, it is recommended to request bookings at least 3 weeks in advance.
Cancellation PolicyPrior to scheduling/booking a date for this experience, Cloud 9 Living's standard return and exchange policy shall apply. Once you have received a booking confirmation, cancellations are not allowed, however you may reschedule up to 72 hours prior to your booked date by contacting your experience provider directly. If you reschedule within 24-72 hours of your booked date, a fee of 50% of your experience value will apply. Failure to appear on your booked date or reschedule within the policy will result in the loss of the value of your experience.
Experience IDACT-MSP-0006
Is this experience safe?
Safety is the number one priority. All participants go through classroom training and will receive one-on-one guidance from our highly trained instructors. All participants are equipped with hands-free radio communication devices and will be in contact with their instructor at all times during the adventure. Finally, all equipment contains remote shut-off devices so that instructors can turn off the machine at any time during activitity if necessary.
Do I need a driver's license?
No, a driver's license is not required. Participants must be at least 14 years of age. Minors must be accompanied by parents or legal guardians.
Can more than one person do this experience at once?
All of our equipment is single rider only. If people want to experience this together we can run two individuals separately at the same time to experience the sandbox together. An example could be one individual would be running the excavator while the other person is running the bulldozer and the instructors could coordinate some activities together. Please note if you would like to do this experience with someone else at the time of booking.
Can I split the experience with someone else?
Yes, when purchasing you can choose between two different pricing options: either do the whole experience yourself, or purchase the Ultimate Sandbox for 2 to split the package time with another person.
Are media packages available for purchase?
Yes, media packages are available for purchase on the day of your experience, however, they are subject to availability.
Can I bring my GoPro camera on the experience?
Yes, GoPro's are allowed so long as they are securely fastened and are not a safety concern.
- Is this experience safe?


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Hi all
I wonder if anyone has much experience of the subject?
I ask as for a long time now my lower back has clicked/popped.
These days my ribs, collar bone, neck, upper and lower back are all tight and crack/pop etc. A few years back I ran 3 marathons and was having regular sports massage....at the time she said that she suspected my pelvis is twisted due to how my leg hangs from my hips.
I'm overweight, play golf (obviously) and weight lifting.....all stuff that isn't conducive to a healthy back.
What should I do? whom should I seek out for advice? Any + or - with any of these people?


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Rust Check Kingston
102 Fraser St. Kingston
Rust Check
Rust CheckRust Check is a premier automobile body panel protectant that has been used successfully since 1973. It is a light liquid product that is applied inside body sections as a pressurized spray.
Crevice areas hidden inside body sections, such as joints, folds, seams, and spot welds therein are the places where corrosion starts and spreads from. Rust Check has the light liquid consistency and the active additives necessary to penetrate deeply into and protect the many vulnerable crevices found in today's vehicles.
Rust Check protects metals by displacing moisture and treating the surfaces with highly effective corrosion inhibitors. The corrosion inhibitors form an adsorbed (bonded) layer on the metal surfaces. This microscopic layer acts like a series of tiny umbrellas, shielding the surfaces from water molecules. Just as a car battery will not work without its electrolyte, metal corrosion will not occur if moisture does not contact the metal.
Coat & Protect (Dripless)As an option, Rust Check offers a unique two step application process designed specifically to provide highly effective corrosion protection, while offering substantial cosmetic benefits in the under carriage appearance of your vehicle.
Rust Check Coat & Protect is a thicker version of Rust Check that forms a moisture and abrasion-resistant protective coating that retains the same highly effective characteristics as Rust Check and is highly self-healing.
Rust Check Coat & Protect provides the required protection for your vehicle undercarriage, as well as a more attractive appearance.
We offer Dripless as an under only, an add on, or you get it in our Gold and Platinum packages.
Please Note: Dripless will still drip, it just drips less than the Traditional. Applications on or right before hot days may result in more dripping than normal.
Black Coat & ProtectThe Ultimate Rust Check for Trucks and SUVs is now available!
The Black Coat keeps your frame and undercarriage looking good and protects it from corrosion.
It is also a penetrating formula that moves through rust (like our Amber Coat & Protect) to protect the solid metal underneith.
We apply it to your wheel wells, outside frame, and axles. It is Self-healing and does not dry or crack, making it perfect for both old or new vehicles.
We offer Black as an under only, an add on, or in our NEW Platinum Package.
FREE InspectionAre you buying a used car or truck? Bring the vehicle to the Corrosion Specialists at Rust Check!
Cars and trucks are an expensive and important purchase. Make sure you're buying a good safe vehicle, before you buy.
We offer a FREE Corrosion Inspection of any vehicle and a written corrosion report.
We check for corrosion:
Not every repair goes through insurance, so an accident repair may not be listed on Car Fax or other historical reports. We can often tell you if the vehicle has been in an accident or repaired. We can also help you make an informed decision about your current vehicle, is it still safe? Using another rust prevention product? Our inspection can often tell you how well it's working.
Contact us at 613-542-2305 and make a FREE appointment for your FREE Inspection today!
Keep your Fleet on the street with Rust Check!Our Goal is to help extend the life of your fleet, and in turn helping to boost your bottom line.
Fleets come in many forms. We have 3 Classifications of Fleets at Rust Check Kingston.
Personal Fleet, for 4 or more vehicles. Business Fleets for small to large Businesses, for 4 or more vehicles. Trade Fleets for Garages and similar businesses.
A Yearly Rust Check will Dramatically cut vehicle replacement cost over the next 10 years and longer.
This will in turn Free up money at the local level for salaries, advertising, expansion, project or even more vehicles, ect...
Rust Check will maintain the safety and appearance of your vehicles, while helping to cut fleet repair costs with mechanical and body maintenance.
Waiting one year to replace an existing vehicle and you save $5,400 in vehicle purchase payments ($450 per month estimate). Multiply that by the number of vehicles in your fleet and you have substantial savings. For 5 vehicles, that comes to a yearly savings of $27,000 - for 10 vehicles you save $54,000. That money stays in your company's hands if your vehicles are kept just one year longer!
If you keep your vehicles 5 more years, you keep $27,000 per vehicle in your pocket. For ten vehicles, that $270,000 in money not spent. That sure makes you look good when that year end performance assessment comes round. Why not make yourself richer instead of the car dealers?
The cost of Rust Check is minimal and the savings are huge. Rust Check can give your business that competitive edge. Let Rust Check put that money into your hands where it belongs!
All fleets receive a special volume pricing on top of that. Even more savings!
Your Employees win too! Your staff gets your special fleet discount on their personal vehicles. This saves them thousands and keeps their cars looking like new. It's a perk that costs you nothing, but is great for company morale. Now you are spreading the savings around!
Contact us today for a quote on your fleet, or come into the store and we can get you set up today!
Price List
Under Only:
Coat & Protect (Dripless):
Black Coat & Protect: $79.95
and classic vehicles.
Full Treatment Car:
Small Truck/Van/Suv's:
Large Trucks/Suv's: $129.95
Treated with our top quality product. Upgrade to Traditional for as little as $15 more!
Dripless add on: $25
Added to any treatment for abrasion resistance, clings to your vehicle, not your driveway!
Black add on: $50Added to any treatment giving a fresh appearance as well as abrasion resistance. Popular with contractors.
Gold Package: $219.95Double the protection. Thicker abrasion resistant Dripless on the frame and wheel wells.
Penetrating traditional in all sheet metal hallows. With a free full mid year re-spray!
Same price for all Vehicles except oversized.
Platinum Package: $239.95The best of the best! Penetrating formula of traditional, combined with dripless abrasion protection
and our new Black for areas such as your frame and wheel wells. Also includes a free full mid year re-spray!
Same price for all Vehicles except oversized.
Additonal Services Available:
Grit Wash: $30Available with or without a Rust Check Treatment.
Please advise when booking an appointment as additional time is needed. Aproximately 30 - 60 min.
Please note: If your vehicle is too dirty to treat we will advise before washing and/or charging.
In winter months, ice and snow may be washed off at no additional cost.
No Holes Treatment: $30Have a show car? Not comfortable with holes being drilled in your vehicle?
Why does it cost more? Extra training is needed for Technicians to have the proper skill to treat as many
areas as possible. This may also require more time. Up to 30 min longer on some vehicles.
Touch Up Add On: $29.95If you have had a full treatment of Traditional, or Coat and Protect, and wish to add on or upgrade
your touch up, you may do so 6 - 8 months after a treatment. Call for more detals.
We also accept competitor coupons. See in store for details.


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Tech Bytes, Monday January 28
Welcome to Data Privacy Day! To celebrate the fact that, well, we don't have very much….
- Department of Defense plans a massive expansion to ensure military control over internet-based communications. Oh, and a massive contractor boondoggle in the midst of forced austerity on everyone else.
- Facebook and Instagram are locking people out of their accounts and asking for uploaded images of government-issued IDs and birth certificates in order to regain access.
- An appeals court says that Twitter must hand over information to the government in the Wikileaks probe. The government doesn't need a warrant, the reasons why it is seeking the information remains sealed, and the subscribers have no first amendment rights to access the information lest they be "tipped off" about the government's investigation. Change!
- Blackrock coughs up $80 million for a stake in Twitter, buying stock from about 2 dozen employees and giving the company some breathing room before its inevitable IPO.
- I'm not even sure what a Fashion Hackathon is, but it seems to be extremely popular and very sold out.
- Yahoo stock has surged 30% since Melissa Mayer took the helm, but analysts will be looking for revenues when the company reports its earnings later today.
- Shark jumping in our time: Cosmo wants to do an article on lady hackers. (h/t BetaBeat)
- Eat like Steve Jobs: Ashton Kutcher's pancreas gives out after two days on Jobs' frutarian diet.
- UK Safari users suing Google for tracking them without permission.
- Google blogs about what they do when the government asks them for your information.
- Iran launches a monkey into space, plans to put a man on the moon by 2025. I'm all for the space race over the arms race, but not exactly what I was thinking.
- FAIR gives props to FDL's Kevin Gosztola for reporting that PBS's infomercial on drones was underwritten by drone maker Lockheed Martin, violating NOVA's underwriting rules.
Finally, #YOLO — you only live once, from Saturday Night Live (above). So don't go outside, because the world's a scary place.


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|HOME | McCaw Hall | Timelines | Events
Hall's lighting scheme creates 'melodies for the eyes'
Sunday, June 22, 2003
By Melinda Bargreen
Those huge outdoor mesh screens that extend outward from the west side of McCaw Hall, above the heads of the incoming visitors, are among the most striking design elements of the new hall.
Originally the concept of architect Mark Reddington, they were brought to life by Leni Schwendinger an experienced lighting artist for opera and ballet who has worked at the Bayreuth Festival and who created the "fire" lighting for Seattle Opera's "Ring." She's also a former rock stagehand, and has done lighting projections for Ozzy Osbourne, Styx and Laurie Anderson.
"The idea was to 'open up' the hall by giving those outside a look at what was happening inside," explains New York-based Schwendinger.
At first, the idea was to open things up literally, by showing videos outside of the operas or ballets inside. LED (light-emitting diode) screens, like those billboards that transform from one image to the next, were "way too expensive," Schwendinger says.
Yet, "We wanted to bring drama to the general public," says Schwendinger.
"We asked ourselves, what is the simplest thing we could do? The answer was colored light. But we didn't want a million lights; they have to be changed and maintained, after all. We came up with 213 lights on nine scrims, with colored light that will pass through the scrims at an angle and then blend with other light in a Rothkoesque painting."
Schwendinger created four sequences of lighting that she calls "melodies for the eyes."
"I wanted recognizable color compositions, like a recognizable tune," she says. "I hope the public loves them and gets involved in viewing them, perhaps from a favorite place to stand."
One lighting sequence evokes the Northern Lights with a sense of swirling movement. Vivid aquamarines dominate another, inspired by Wagner's Rheinmaidens, whose music "just haunts me," Schwendinger says.
The colored lights won't be on all the time.
"A 'white state' will be predominant," Schwendinger says, "because otherwise it'd be like hearing the same music over and over and over. Probably we'll have one sequence (of colored lights) per night, with lots of white space around. It will all be automated and pre-programmed."
The programmed sequences are intended to be permanent, though theoretically they could be altered by a computer locked safely in the Phelps Center.
The lights are located about 45 feet above the ground, and are engineered for wind. The scrims are made of stainless steel, the most weather-worthy substance available. Schwendinger had permanence in mind during the design and fabrication process.
"I've wanted for a long time to move out of the theater and into the real world," she says of her work.
"This project is such a great match for my interests and background."
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Birmingham, AL (PRWEB) January 28, 2014
The Braintrust Consulting Group announced that they will host a Certified Scrum Product Owner class February 12-13, 2014 in Salt Lake City, Utah. This announcement was part of Braintrust's unveiling of their national class schedule for 2014.
The two-day Certified Scrum Product Owner class offers attendees an in-depth immersion into the world of Agile Product Management. Scrum is a simple yet incredibly powerful set of principles and practices that help teams deliver products in short cycles, enabling fast feedback, continual improvement, and rapid adaptation to change. As the leading Agile development framework, Scrum has predominantly been used for software development, but it is also proving to be effective in efforts far beyond. This class is full of practical, real world techniques that attendees can implement immediately. Hands-on exercises demonstrate key concepts and let attendees experience the benefits of Scrum firsthand.
This class is ideal for Product Managers/Business Analysts, Functional/Operational Managers, Project Sponsors, and IT Leadership (Managers/Directors/VPs/CIOs/CTOs). Members of the Project Management Institute will earn 14 Professional Development Units (PDUs) toward maintaining their existing credentials by attending this class.
Braintrust President, Brian Rabon said, "As part of Salt Lake City's business community, we are proud to host these classes and contribute to the growth of IT industry talent. Technology-based companies are an integral part of Salt Lake City's economy, and Braintrust offers world-class training to this growing technology industry that ranks as one of the top in the U.S."
The class will be taught by Brian Rabon, CST, PMP. Rabon is the president of The Braintrust Consulting Group and holds a Bachelor's Degree in Computer Science from Auburn University and a Master's Degree in Electrical Engineering from the University of Alabama at Birmingham. Throughout his 16 years of IT industry experience, Brian has applied Agile methods in order to successfully delivery working product to his customers.
As a takeaway, participants will receive a printed class manual, Scrum reference card and thumbdrive loaded with articles, class exercises, whitepaper, and more.
To sign up and learn more details about the Certified Scrum Product Owner two-day class, as well as other upcoming Braintrust classes, please visit: http://braintrustgroup.com/class/certified-scrum-product-owner-cspo-salt-lake-city-ut-12-13-february-2014/.
About The Braintrust Consulting Group
With offices in Birmingham, Alabama, Los Angeles, California, and Salt Lake City, Utah. The Braintrust Consulting Group is a worldwide leader in Agile transformations. Through practical, hands-on training and enterprise and team coaching, we help our clients learn, plan, and implement Agile processes, such as Scrum and Kanban. Our goal is to teach our clients how to increase predictability of delivery, decrease time-to-market, and improve overall client satisfaction. http://www.braintrustgroup.com


text: Seeing as we're in the midst of a "tattoo takeover," we figured we'd take a few minutes to talk about celebrity tattoos. They've become so commonplace that it's almost rare to see a celebrity who doesn't have one peeking out from their sleeves or their gowns. PHOTOS: 10 Iconic Tattoos In Film But have you ever stopped to wonder about your favorite star's tats? What they mean, why they're there, or how they've affected lives and careers? Sometimes, the stories surrounding these markings are more interesting than the designs themselves. READ: 10 Things You Didn't Know About Tattoos We researched a slew of our favorite celebrities to bring you the tales behind their tattoos. Have a look below:


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Republicans will hold a primary next week—Tuesday, June 12—to select a candidate to run for the United States Senate as well as the House of Representatives.
By Laura Enderson
Intern Writer
Editor's note: This is the second in a series of local and other places/activities for your family to enjoy this summer.
Summer is the time to take a vacation from work or encourage the kids to get off the couch for a day or two. If the family is still in need of a few new ideas or just need to be reminded of some of Virginia's classics, here are a few family friendly travel ideas for this upcoming week.
Annette Carter believes that Alzheimer's doesn't get the attention it should.
She notes that there are all sorts of activities around to raise awareness about cancer, but little about Alzheimer's. Not that she begrudges the attention that cancer gets, but she would like to see more done to raise awareness about the devastating brain disease known as Alzheimer's.
Changes are being made to the city Municipal Building as city officials install an accessibility ramp, along with rails and an automatic door for easier access for the public.
"It's an improvement on access abilities," said Charles Kolakowski, Bedford's city manager. "It should be very helpful for people that have difficulty with stairs."
Central Virginia Community College (CVCC) got a new face in workforce development this year.
Dr. Ruth Z. Hendrick came on board in February as vice president for workforce development and continuing education. Her job is to work with companies to provide the worker training that they need. In this role, she will work with both existing businesses as well as new businesses that come into the area. She also looks for grants to pay for this.
George Allen made a stop in Bedford, Friday, during a campaign tour. Allen is seeking the Republican nomination to run for Senate this fall. The nomination will be decided in a primary scheduled for June 12.
Allen stopped by several Bridge Street businesses talking with owners before holding a small rally in a hallway in the County Administration Building. One stop was Frederic's Flowers, where Allen asked owner Ricky Wilkerson what could be done to help small businesses.
Bedford continues to look for ways to promote its artisan community.
Close to 50 people turned out for a presentation on establishing an Artisan Trail in the Bedford area.
"Bedford is ready for this," said Brigitte Peterson, who introduced the program. Peterson works for Bedford County.
"I am the procurement department," she said when asked what her job is. "Right now I am trying to procure an Artisan Trail."
By Tyler Flynn
Intern Writer
The phrase "one man's trash is another man's treasure" is truly being taken to heart by some environmentally conscious students in Bedford County.
Huddleston Elementary School, which has partnered with the New Jersey-based company TerraCycle, has been recognized by the organization for the effectiveness of its recycling initiatives.
Laura Enderson
Intern Writer
Last Tuesday, Bedford County Circuit Court Judge James Updike handed down a sentence on two counts of DUI maiming to 42-year-old Elizabeth Doris Coe.
She received two years in prison with five years suspended for each of the two counts of DUI maiming, and 12 months in prison and a $1,000 fine for one count of DUI, totaling 11 years suspended after five years served.
A cleanup operation following a fuel tanker crash last week on U.S. 460 near Montvale, which claimed the life of the truck driver , may take some time.
In the meantime, the crash has caused some county supervisors to call for the road's hazardous curves to be corrected.
Copyright © 2018
The Bedford Bulletin is your source for local news, sports, events, and information in Bedford County and Bedford, VA and the surrounding area.


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Artisan Prep Art Studio + Gallery
An edgy San Diego Art Studio + Gallery that will infuse an appreciation of art while inspiring the people who live it.
- Stage Product In Development
- Industry Consumer Products
- Location San Diego, CA, USA
- Currency USD
- Founded October 2012
- Employees 1
- Website ArtisanPrep.com
Company Summary
Artisan Prep Art Studio + Gallery represents an eclectic mix of artists pushing the boundaries of what is modern and what is contemporary. Artisan Prep is unlike other galleries/art studios, as it stands out with its dynamic space and innovative daily studio classes. The gallery hosts an array of art and design talks, presentations, exhibitions, and creative interpretation. A wormhole of artful learning for every level of expertise.
Stacie DaigleFounder/ CEO
I have worked in Advertising + PR for the past 7 years. In that span I have made connections with many high-profile people, media, and national organizations. I come from a family of artists so this is a passion project for me and I am very excited for this next chapter.


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sf_el_fx Module Guide Resources
Information on the module guide itself and the associated resources and known issues are available here.
The FileX Port Block Media Framework module, implemented on sf_el_fx, supports the Express logic FileX system, a complete FAT format media and file management system for deeply embedded applications. The FileX Port Block Media Framework module provides I/O calls for FileX to access Synergy Media drivers through the Block Media Interface and adaptation layers. The SD/MMC Driver and the SDIO Driver are implemented on r_sdmmc and are used to read/write and control SD/MMC media devices as well as SDIO cards. The sf_el_fx module uses the SD/MMC peripherals on the Synergy MCU.
- The FileX Port Block Media Framework module features include:
- Unlimited FileX objects (media, directories,
- and files)
- Dynamic FileX object creation/deletion
- Flexible memory usage
- Size scales automatically
- Small footprint
- Complete integration with ThreadX
- SD bus interface
- Compatible with SD memory card and SDIO card
- Transfer bus mode selectable from 4-bit wide bus mode or 1-bit default bus mode
- Compatible with SD, SDHC, and SDXC formats
- SD and MMC shared
- DMAC and DTC triggerable by the SBFAI interrupt SD buffer is read and write accessible using the DMAC
- Card detect function
- Write protect support
- MMC bus interface transfer bus mode selectable from 1-bit, 4-bit, or 8-bit
Module Guide
The FileX Port Block Media Framework module guide is targeted for SSP 1.2.0 and above and the SK-S7G2 Kit.
The most recent versions of the FileX Port Block Media Framework module guide application note, application project and import guide are available here.
Module Guide Resources
The following application projects are available from the Renesas web site at the referenced url.
- The FileX Port Block Media Framework module is used in the Developer Examples available on the Synergy Gallery here. Simply download the zip file and import the FileX Port Block Media example into your ISDE. See the Knowledge Base article here for more information.
Known issues
- Refer to the SSP release notes for known issues, available here.


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We are one of the many chapters of the International MOMS Club® (Moms Offering Moms Support), a non-profit organization aimed at providing support for stay-at-home mothers.
We are a support group designed just for you: the at-home mother, part-time working mother, and home based business mother. You are interested in the world around you, want a variety of activities for you and your children, and are proud of your choice of at-home mothering, or simply getting involved in your child's life. We are here for YOU, to provide support, activities and friendship for you and your kids during the day, when you need it the most!
For more information about our chapter of the MOMS Club® of Mandeville please email us at [email protected]
If you have questions regarding another chapter anywhere in the U.S. visit the International MOMS Club® website at www.momsclub.org.
The name "MOMS Club®" and the mother/children logo are registered service marks of International MOMS Club® and are used with permission. Neither the MOMS Club® of Mandeville Area, LA nor the international MOMS Club® endorse any advertised service.


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July. 15 weeks left before I am on study leave and high school is basically over, forever. I can't wait. Also, a two week holiday! Also, it's winter!
School was crazy in June. There was assessments in every subject. I had a Speech and Drama exam, which was a five minute talk, two poems, a characterisation plus the discussion topics. Drama rehearsals marched on. Football finally got underway, and is awesome (as expected).
Arts week, which is a week my school dedicates to celebrating the Arts came to an end today (I'll try to do a post that goes into some more detail about it). The week was amazing, but also stressful and not without it's moments. I performed in the two soiree's we had on, as an MC, in the dance group and a devised drama piece, which was awesome.
To be honest, I don't really have much to say because I'm pretty much buried in work 24/7. And if I'm not studying or at school, then I'm reading or sleeping. I also squeezed in the writing of about 500 words.
I hit 100 books this month! I'm currently reading my 102 book for the year. Guys!! The Wrath and the Dawn! The Raven King! The first two Firebird Series books! It was a good reading month. Talk to me if you have read these books, I need someone to flail with!


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There's a common belief that temperature calibration isn't possible in digital devices. It is a sane belief but still, there's a working logic for this operation. When you enter a desired value to calibrate the device, the internal temperature of the thermistor is manipulated accordingly. This is exactly how it works. Following are top 10 tips on temperature calibration.
1. Select the best thermistor
The Platinum Resistance Thermometer is the most accurate thermistor known to the developers at present. The readings are accurate up to a few decimal places if measured digitally. If you aren't familiar with transducers, then you can go with the analog display. The readings on the scales are accurate too.
2. Avoid usage of fluid chemicals
Try to stick to the dry-well; as the name suggests, it is dry and almost 0% moisture is present. Calibration bath is physically unpleasant as it contains viscous fluids. A dry-well is an excellent way to deal with messy fluids.
3. Keep an extra thermometer
It is recommended that you carry two or more thermometers to minimize the reading errors. Read a number of thermal devices at once and tally the readings. If the readings differ a little, consider the average.
4. Use a thermal source
While calibrating the device, make use of an external thermal source to provide heat to the device.For instance, if you wish to reduce the temperature by two degrees; then make contact of an external source to reduce the temperature by two degrees. Similarly, operate the thermal device to increase the heat. The thermal source must be digital and should be accurate up to at least two decimal places. Digital devices are always convenient.


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What is Plant Protein?
As the name suggests, plant protein is the protein from plants. Just like protein from other sources, it can be used to promote lean gains, fat loss, and muscle recovery.
Where Does Plant Protein Come From?
Technically, any protein from a plant origin can be defined as a plant protein. However, the most common forms of plant protein are soy, pea, and rice.
Plant Protein Benefits
Although whey protein is the most commonly used, and arguably, best form of protein, it is not suitable for everyone. Vegans choose not to consume animal products, and milk allergy suffers are unable to use many forms of whey proteins. Plant proteins are therefore a viable alternative.
Out of all the plant proteins, soy protein is probably the best known and best studied. There is strong evidence supporting soy protein for use as a supplement for bodybuilding and exercise. This has been covered in great detail in our "Soy Protein" article. Studies have shown that soy protein is rapidly digested and (Tang et al, 2009) and contributes to lean gains (Brown et al, 2004). Results such as this also suggest that soy protein is one of the best plant proteins, and it is also contains a complete amino acid profile. However, in cases where individuals have soy allergies and wish to remain with a plant protein, other sources such as rice and pea are also good alternatives.
Plant proteins, depending on their source also have unique nutrients that are absent from animal derived protein sources. For example, soy also contains isoflavones and antioxidants which may be beneficial for general health.
Plant Protein Negatives & Side Effects
Perhaps the largest criticism of plant proteins is that they do not appear to promote an anabolic response as great as whey, especially in the long term (Phillips et al, 2005). However consuming a variety of different plant proteins may be able to improve the anabolic effects of plant proteins, and provide a more diverse range of amino acids.
Each type of plant protein also has its own draw backs. These include allergies and potentially unbalanced amino acid profiles. It is therefore important to research each protein individually.
Plant Protein Recommended Doses & Ingredient Timing
Plant protein can be used to make up part of, or all of your recommended protein intake per day. This can be anywhere between 1 to 2 g/kg bodyweight depending on your goals and level of exercise. Just like other protein, timing for protein intake is important. It has been well established that protein intake before and immediately after exercise is important for muscle gains. This has been covered in detail in our "Supplement Timing" and "Nutrient Timing" articles.
Plant protein Supplements
Plant protein can be found in a variety of different supplements. They can be found as protein powders or in protein bars. Plant protein powders may be classified as natural protein powders, soy proteins, or rice proteins.
Stacking Plant Protein
If you have no dietary restrictions, plant protein can be a good complement to your existing protein supplements. However, if you are after a purely plant protein based stack, then it is recommended that different plant proteins should be stacked to provide optimal nutrients for good gains and general health. Having considered this, plant proteins can be stacked much like any other protein, and works well together with carbohydrates and creatine. This has been covered in great detail in our "How to Stack Supplements" article.
Brown et al (2004), Soy versus whey protein bars: Effects on exercise training impact on lean body mass and antioxidant status. Nutrition Journal, 3 (online)
Phillips et al (2005), Dietary Protein to Support Anabolism with Resistance Exercise in Young Men. J Am Coll Nutr, 24: 1345-1395
Tang et al (2009), Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol, 3: 987-992


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Allure Styling Salon was established in 2005. We consider each client as an individual with his or her own needs and desires. We strive to meet those needs and desires with the best talent available. Experience dedicated professionalism with one of our friendly, talented artists. Your appearance and satisfaction is our highest priority. Call to schedule your next appointment with us and you...
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Vicky is so sweet and does a great job on my highlights!
Allure Styling Salon is located at 300 Goff Mountain Rd in Charleston and has been in the business of Beauty Shops since 2005.
Allure Styling Salon can be found at Goff Mountain Rd 300. The following is offered: Massage Therapy. The entry is present with us since Sep 10, 2010 and was last updated on Nov 14, 2013. In Charleston there are 10 other Massage Therapy. An overview can be found here.
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