Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

Background

The amount and quality of dietary fatty acids can modulate the fat metabolism.

Objective

This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes.

Design

In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile.

Results

The plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (≥ C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05).

Conclusion

Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.

     

Expression of carbonic anhydrase IX in human pancreatic cancer

BACKGROUND: Carbonic anhydrase IX has been linked to cancer development and progression. AIM: To analyse carbonic anhydrase IX expression and anhydrase inhibition in pancreatic cancer and to correlate these findings with p53 expression and microvessel density. MATERIALS AND METHODS: Seventy-seven pancreatic cancers were examined (43 males, 34 females; mean age, 64 years). The anti-carbonic anhydrase IX M75 antibody was used for immunohistochemistry and Western blot analysis. Microvessels were visualized using the anti-CD34 antibody, and p53 expression in cancer cells was assessed with a specific anti-p53 antibody. Quantitative polymerase chain reaction was performed in order to assess carbonic anhydrase IX mRNA levels in the pancreas. Furthermore, pancreatic cancer cell lines were treated with acetazolamide, a carbonic anhydrase inhibitor. RESULTS: In the normal pancreas, carbonic anhydrase IX immunoreactivity was observed at the basolateral membrane of ductal cells in 24 cases (31%). Carbonic anhydrase IX expression was found at the membrane and in the cytoplasm of pancreatic cancer cells in 16 pancreatic cancers (21%). Carbonic anhydrase IX expression was independent of the localization, stage, size, metastases and differentiation of the tumour. p53 expression was significantly more frequent in poorly differentiated cancers (P=0.0323); however, p53 expression and microvessel density were independent of carbonic anhydrase IX expression. Overall, carbonic anhydrase IX expression was not altered in pancreatic cancers vs. adjacent normal pancreatic tissue as assessed by Western blot and quantitative polymerase chain reaction analysis. However, incubation of pancreatic cancer cell lines with acetazolamide led to a significant inhibition of cell proliferation in AsPC-1 and PANC-1 pancreatic cancer cells. CONCLUSION: Carbonic anhydrase IX expression is observed in both ductal epithelial and cancer cells of the pancreas. Although the expression of carbonic anhydrase IX in pancreatic cancer is not associated with angiogenesis or advanced disease, it may well be a target for carbo-anhydrase inhibitors in a subset of pancreatic cancers.     

Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration

BACKGROUND: To evaluate the association of long-term continuous mycophenolate mofetil (MMF) versus azathioprine (AZA) therapy and renal allograft function, as measured by the slope of reciprocal creatinine, we analyzed 49,666 primary renal allograft recipients reported to the United States Renal Data System between October 31, 1988 and June 30, 1998. METHODS: The primary study endpoint was defined as a greater than 20% decrease below a 6-month baseline of 1/serum creatinine (SCr) (slope of reciprocal creatinine) at or beyond 1 year after transplantation. A secondary endpoint was defined as reaching an SCr value greater than 1.6 mg/dL. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to investigate the risk of reaching the study endpoints. Multivariate analyses were corrected for potential confounding covariates. RESULTS: According to the Cox proportional hazard model, 12-month continued therapy of MMF versus AZA was associated with a protective effect against declining renal function, as measured by the slope of reciprocal creatinine (relative risk [RR]=0.84, confidence interval 0.78-0.91, P<0.001). For 24-month continued therapy of MMF versus AZA, MMF was associated with a further decreased risk for a decline in renal function (RR=0.66, confidence interval=0.57-0.77, P<0.001). Furthermore, MMF was associated with a protective effect against reaching the SCr threshold of 1.6 mg/dL (RR=0.80, P<0.001) beyond 12 months posttransplantation. CONCLUSIONS: Continuous use of MMF versus AZA was associated with a protective effect against declining renal function beyond 1 year after transplantation. Further study is needed to confirm that continued MMF therapy is protective against long-term deterioration in renal function.     

The impact of simultaneous pancreas-kidney transplantation on long-term patient survival

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation. We evaluated mortality risks associated with SPK, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. METHODS: A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. RESULTS: Adjusted 10-year patient survival was 67% for SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001). The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was 2-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001). However, the adjusted 5-year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients > or =50 years old (RR=1.38, P=0.81). CONCLUSIONS: Among patients with type 1 DM with end-stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis.     

Comparison of standard and steerable catheters for bile duct cannulation in ERCP

BACKGROUND AND STUDY AIMS: The aim of the study was to compare two steerable endoscopic retrograde cholangiopancreatography (ERCP) catheters with regard to speed and safety in cannulating the common bile duct. PATIENTS AND METHODS: A standard cannula, a short-nosed sphincterotome, and a bendable catheter were used. At two tertiary centres, a total of 312 patients were randomly assigned to receive treatment with one of three catheters and either by a trainee or an expert endoscopist. When cannulation failed, a further attempt was made with a different catheter. If this failed, a change in operator or other manoeuvres followed. The following were assessed: time to cholangiography and deep cannulation, number of attempts and success rates of cannulation, number of pancreatic duct injections, success of catheter cross-over, and complication rates. RESULTS: Both steerable catheters were significantly better for the initial cholangiogram than the standard catheter (standard catheter 75 %, bendable catheter 84 %, sphincterotome 88 %; P = 0.038), with no significant differences between the bendable catheter and the sphincterotome. Both were also better for deep cannulation of the bile duct (standard cannula 66 %, bendable catheter 69 %, sphincterotome 78 %; P = 0.15). When the standard catheter failed, a steerable catheter succeeded in 26 % of cases. Trainees experienced greater benefit from using steerable catheters. For experts, the bendable catheter was the quickest to achieve cholangiography and deep cannulation. Further manoeuvres had an 85-90 % success rate in allowing biliary access. Twenty of 23 needle-knife papillotomies (87 %) were successful when other methods had failed. The overall ERCP success rate was 97 %. Pancreatitis occurred in 5.3 % of cases. CONCLUSIONS: Steerable catheters allow faster access and can succeed when a standard catheter fails. If cannulation is difficult, changing the catheter should be considered at an early stage. Needle-knife papillotomy is a successful technique in expert hands.     

Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation

BACKGROUND: Citrate anticoagulation is commonly used for continuous venovenous hemodialysis (CVVHD) to minimize the risk of bleeding complications. We have previously reported a liver failure patient undergoing citrate-based CVVHD with elevated serum total to ionized calcium ratio. Diminished liver metabolism of citrate with resultant elevated systemic citrate was thought to be the cause. METHODS: To determine the incidence and clinical significance of an elevated total to ionized calcium ratio during citrate-based CVVHD, 161 patients undergoing citrate-based CVVHD were screened for the presence of an elevated total to ionized calcium ratio (the subset with increased total to ionized calcium ratio comprised the study group). Because all patients in the study group had liver failure, two control groups of patients with normal total to ionized calcium ratios were formed-those without liver failure (control I) and those with liver failure (control II). RESULTS: An elevated total to ionized calcium ratio was detected in 12% of all patients. Thirty-three percent of liver failure patients demonstrated an elevated total to ionized calcium ratio. The study group demonstrated significantly higher mean total calcium levels, significantly lower mean ionized calcium levels, and significantly higher mean total to ionized calcium ratios than controls. As a result, the study group also had significantly increased mean calcium chloride replacement requirements in comparison with controls. The mean calcium to citrate infusion ratio was elevated in the study group in comparison with controls. An elevated total to ionized calcium ratio was associated with increased mortality in comparison with controls. No patients suffered complications from ionized hypocalcemia or elevated serum total calcium. CONCLUSIONS: Systemic citrate accumulation as evidenced by an elevated total to ionized calcium ratio occurs commonly in patients requiring CVVHD using citrate-based regional anticoagulation. Observing changes in the total to ionized calcium ratio can aid in early detection of patients with hepatic failure who are unable to appropriately metabolize citrate and will require calcium chloride infusion rates significantly above normal.