Intrafamilial associations of lipid profiles and the role of nutrition: the Tehran lipid and glucose study.

BACKGROUND: The role of gene and environment in the genesis of abnormal lipid profile is still a controversial issue. OBJECTIVE: To clarify the importance of certain parental risk factors associated with lipid profiles of children and adolescents. METHODS: We conducted this cross-sectional population-based study in district 13 in the east of metropolitan Tehran. One hundred and thirteen eligible families comprising 455 subjects (including 229 offspring, aged 5-25 years) were enrolled into the study. Anthropometric data were measured using a standard protocol. To measure lipid profiles, venous blood was obtained in the morning after the subjects had fasted for 12-14 h overnight. Dietary intakes were assessed by means of a 2-day dietary recall questionnaire. RESULTS: The chances of having elevated serum total cholesterol were higher in sons of fathers with high cholesterol intake (OR = 3.1; CI = 1.1-9.2) and mothers with high saturated fatty acid (SFA) intake (3.4; 1.1-10.8). Positive correlations were seen between the energy intake of fathers and serum total cholesterol of their daughters (r = 0.34, p < 0.01); between the SFA intake of fathers and serum triglycerides (TGs) of their sons (0.29, p < 0.01) and between mothers' body mass index and daughters' serum TGs (0.23, p < 0.03). The chances of having low serum high-density lipoprotein cholesterol were lower in sons of mothers with high carbohydrate intake (11.0; 2.8-42.8) and mothers with high serum high-density lipoprotein cholesterol (6.8; 1.7-27.0). There were higher chances of having elevated serum low-density lipoprotein cholesterol in sons with fathers having high SFA intake (4.5; 1.4-14.3), with mothers having high serum TGs (6.1; 1.3-29.0) and with mothers having high cholesterol intake (4.3; 1.2-15.2). CONCLUSION: The results indicate independent associations between diet contents and the lipid profiles of parents and their offspring as well as between lipid profiles and diet contents among spouses.

Islet isolation and transplantation outcomes of pancreas preserved with University of Wisconsin solution versus two-layer method using preoxygenated perfluorocarbon.

BACKGROUND: Previous small clinical trials indicate that the two-layer method (TLM) for pancreas preservation improves islet isolation outcome. However, the effect of TLM has not been evaluated in large-scale study. In addition, a direct benefit of TLM on islet transplantation outcome has not been addressed in the setting of any randomized controlled trials. METHODS: Between April 2003 and October 2005, human pancreata from brain-dead donors were preserved by TLM using preoxygenated perfluorocarbon (n = 75) or in University of Wisconsin (UW) solution (n = 91) prior to islet isolation. Islet isolation and transplantation outcomes were compared between the two groups. RESULTS: We did not find any significant differences in adenosine triphosphate content in pancreatic tissue after preservation, pre and postpurification islet yields, in vitro insulin secretory function, or utilization ratio of transplantation between the two groups. Transplanted mass and functional viability of islet isolated from TLM-preserved pancreas were similar to those from UW-preserved pancreas. Patients receiving the TLM-islet or the UW-islet showed a marked decrease in insulin requirement after transplantation. However, no significant difference was observed in a decrease in insulin requirement between patients receiving the TLM-islet and the UW-islet. CONCLUSIONS: No beneficial effect of TLM on islet isolation and transplantation outcomes was observed. Our findings bring into question the true merit of routine use of TLM prior to islet isolation.

Comparison of cooling systems during islet purification.

Islet isolation is a complex procedure that includes digestion and purification of pancreatic tissue. As we move towards clinical regulatory control and standardization, understanding of the detailed stages of the procedure have become increasingly important. Purification on a COBE 2991 density gradient allows human islets to be separated from a large volume of acinar tissue. Cooling the gradient and tissue is thought to be important to reduce metabolic activity but cooling systems for the gradient are expensive, with limited availability. In this study, the efficiency of cooling methods for the COBE 2991 cell separator has been investigated. The two cooling systems were: a) COBE 2991 modified internally to allow coolant (polyethylene glycol) from a chiller to circulate either side of the spindle and around the bowl (original system), and b) an air-cooled system using an air conditioner to blow cold air into the bowl from above (air cooler system). Cooling required 20 min for the original system and temperature was stabilized within 4-7 degrees C. The air system cooled rapidly but was not stable. There was an increase in the temperature of the medium with using both systems during centrifugation because of heat generated by the COBE machine; however, the temperature of the medium after centrifugation with the air system was significantly higher than that with the original system (13.3 +/- 0.2 degrees C vs. 8.7 +/- 0.7 degrees C, p < 0.05). The original cooler system was found to be more efficient at reducing heat generated by the COBE machine than the air system. Further investigation of the importance of the recorded temperatures is required.

Ameliorating injury during preservation and isolation of human islets using the two-layer method with perfluorocarbon and UW solution.

This study assessed the effects of a two-layer method (TLM), using perfluorocarbon and UW solution, on the quality of human pancreata following storage and islet yield/function after isolation. In part A, TLM was applied immediately after procurement and the energetic profile was compared to a group treated with UW solution only (control) throughout 24-h storage. In part B, cadaveric human pancreata were procured and subjected to a TLM after cold storage in UW solution (TLM group) or UW solution (control group). Energetics, lipid peroxidation, and islet recovery/function were assessed after preservation at 4 degrees C. In part A, after 9-h storage, the energetic profile (ATP, ATP/ADP, energy charge) for the TLM group was superior to controls. In part B, TLM treatment resulted in consistently greater ATP, ATP/ADP, and energy charge values than with storage in UW solution alone (p < 0.05). UW treatment resulted in 40% greater peroxidative damage than in the TLM group (p < 0.05). Islet recovery and functional viability were 30-40% higher following TLM treatment (p < 0.05). These data support the hypothesis that islet viability and yields can be significantly improved using a brief period of TLM treatment following conventional UW storage; reduced energetic and oxidative stress are implicated as potential mechanisms.

Current status of clinical islet cell transplantation.

Clinical outcomes of pancreas transplantation were superior to that of islet transplantation until the introduction of the Edmonton protocol. Significant advances in islet isolation and purification technology, novel immunosuppression and tolerance strategies, and effective antiviral prophylaxis have renewed interest in clinical islet transplantation for the treatment of diabetes mellitus. The introduction of a steroid-free antirejection protocol and islets prepared from two donors led to high rates of insulin independence. The Edmonton protocol has been successfully replicated by other centers in an international multicenter trial. A number of key refinements in pancreas transportation, islet preparation, and newer immunological conditioning and induction therapies have led to continued advancement through extensive collaboration between key centers. This chapter provides an overview of the history of islet transplantation followed by a discussion of the state of the art of clinical islet transplantation. The challenges facing the clinician-scientist in the 21st century are also presented in this review.

Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells.

Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.

Supply of human allograft tissue in Canada.

There is relatively little known about the supply for allograft tissues in Canada. The major aim of this study is to quantify the current or "Known Supply" of human allograft tissue (bone, tendons, soft tissue, cardiovascular, ocular and skin) from known tissue banks in Canada, to estimate the "Unknown Supply" of human allograft tissue available to Canadian users from other sources, and to investigate the nature and source of these tissue products. Two surveys were developed; one for tissue banks processing one or more tissue types and the other specific to eye banks. Thirty nine sites were initially identified as potential tissue bank respondent sites. Of the 39 sites, 29 sites indicated that they were interested in participating or would consider completing the survey. A survey package and a self-addressed courier envelope were couriered to each of 29 sites. A three week response time was indicated. The project consultants conducted telephone and email follow-up for incomplete data. Unknown supply was estimated by 5 methods. Twenty-eight of 29 sites (97%) completed and returned surveys. Over the past year, respondents reported a total of 5,691 donors (1,550 living and 4,141 cadaveric donors). Including cancellous ground bone, there were 10,729 tissue products produced by the respondent banks. Of these, 71% were produced by accredited banks and 32% were ocular tissues. Total predicted shortfall of allograft tissues was 31,860-66,481 grafts. Through estimating Current supply, and compiling additional qualitative information, this study has provided a snapshot of the current Canadian supply and shortfall of allograft tissue grafts.

Demand for human allograft tissue in Canada.

There is relatively little known about the demand for allograft tissues in Canada. The Canadian Council for Donation and Transplantation (CCDT) is a national advisory body that undertook a comprehensive "market survey" to estimate surgical demand for human allograft tissues in Canada. The report "Demand for Human Allograft Tissue in Canada" reflects survey results sent to 5 prominent User Groups. User Groups were identified as orthopaedic surgeons; neurosurgeons; corneal transplant surgeons; plastic surgeons, specifically those at Canadian Burn Units; and cardiac surgeons (adult and paediatric surgery). The demand for allograft grafts was determined and then extrapolated across the total User Group and then increases in allograft tissue use over the next 1-2 years across User Groups were predicted. The overall response rate for the survey was 21.4%. It varied from a low of 19.6% for the orthopaedic survey to a high of 40.5% for the corneal survey. The estimated current demand for allograft tissue in Canada ranges from a low of 34,442 grafts per year to a high of 62,098 grafts per year. The predicted increase in use of allograft tissue over the next 1-2 year period would suggest that annual demand could rise to somewhere in the range of 42,589-72,210 grafts. The highest rated preferences (98% and 94%) were for accredited and Canadian tissue banks, respectively. This study represents a key step in addressing the paucity of information concerning the demand for allograft tissue in Canada.

Cardiovascular risk factors in the elderly: the Tehran Lipid and Glucose Study.

BACKGROUND: Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. Because the proportion of elderly individuals in the population is on the rise, this study was conducted to determine the prevalence of cardiovascular risk factors among the Tehran urban elderly population. DESIGN AND METHODS: Among 15,005 urban individuals of 3 years old and over who had been chosen in a cross-sectional phase of a longitudinal study in Tehran, there were 1,799 people aged 60 years and over. The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus and obesity were determined in this population. Dietary intake was assessed in a subsidiary of 54 people by means of two 24 h dietary recalls. RESULTS: The percentage of women with two or more cardiovascular disease risk factors was significantly greater than in men (74% compared with 53%, P < 0.001). One fourth of men and 55% of women had high serum cholesterol levels (>/=240 mg/dl). The prevalence of diabetes mellitus and impaired glucose tolerance was 24% and 21% in men and 29% and 20% in women, respectively. The prevalence of obesity (body mass index >/=30 kg/m(2)) was 15% for men and 36% for women. Fifty-five per cent of men and 94% of women had high waist-to-hip ratios (>0.95 in men and >0.8 in women). The mean percentage values of energy intake derived from carbohydrate, protein and fat were 60.5 +/- 8.0, 11.5 +/- 2.0 and 27.8 +/- 8.9, respectively. CONCLUSIONS: The prevalence of cardiovascular risk factors among the Tehran urban elderly population is high. Some efforts should be made to reverse the recent trend towards increasing age-related mortality and morbidity rates of coronary heart disease.