One-year impact of bariatric surgery on serum anti-Mullerian-hormone levels in severely obese women.

INTRODUCTION: Although bariatric surgery seems to increase spontaneous fertility by improving ovulatory function in young women, its impact on ovarian reserve remains largely unknown. OBJECTIVE: To evaluate changes in serum anti-Mullerian hormone (AMH) levels in reproductive-age severely obese women after bariatric surgery (BS). METHODS: AMH levels were measured retrospectively in 39 women (mean age 34.6 ± 1.1 years, range 18-45) that underwent a sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) at baseline, and 6 and 12 months after BS. Metabolic and micronutrient status, including fasting plasma insulin and glucose, HOMA-IR, leptin, adiponectin, calcium, albumin, transthyretin, ferritin, vitamins (B9, B12, B1, A, E, D), zinc, and selenium, were assessed in all patients before and 1 year after BS. RESULTS: Of the patients, 79% had class-3 obesity. At 6 and 12 months, mean total weight losses (TWL) were 26 and 30%; mean excess weight losses (EWL) were 61.7 and 70.2%. Compared to baseline, AMH levels significantly decreased by 18% at 6 months, and 32% at 12 months post-operatively (p = 0.010 and p = 0.001, respectively). There was no correlation between AMH variation and changes in metabolic parameters or micronutrient levels. Remarkably, changes in AMH levels did not differ between sleeve and RYGB patients and were not correlated with EWL. CONCLUSION: This pilot study shows a drastic reduction in AMH levels at 1 year after BS in reproductive-age severely obese women, which was not related to weight loss: this suggests a negative impact of BS on ovarian reserve, at least in the short term.

A mutation in the Gardos channel is associated with hereditary xerocytosis.

The Gardos channel is a Ca(2+)-sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos channel in 2 unrelated families and its association with chronic hemolysis and dehydrated cells, also referred to as hereditary xerocytosis (HX). The affected individuals present chronic anemia that varies in severity. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. The missense mutation concerns a highly conserved residue among species, located in the region interacting with Calmodulin and responsible for the channel opening and the K(+) efflux. Using 2-microelectrode experiments on Xenopus oocytes and patch-clamp electrophysiology on HEK293 cells, we demonstrated that the mutated channel exhibits a higher activity and a higher Ca(2+) sensitivity compared with the wild-type (WT) channel. The mutated channel remains sensitive to inhibition suggesting that treatment of this type of HX by a specific inhibitor of the Gardos channel could be considered. The identification of a KCNN4 mutation associated with chronic hemolysis constitutes the first report of a human disease caused by a defect of the Gardos channel.

Influence of diet and sample collection time on 77 laboratory tests on healthy adults.

OBJECTIVES: We studied the effect of a standardized breakfast or lunch before blood sampling on 77 analytes. DESIGN AND METHODS: The mean difference between assays from 20 healthy adults was calculated on blood samples taken before and after food intake. Significant differences were tested using two-tailed Student t-test and compared to the acceptable limits derived from analytical and intraindividual biological variation. RESULTS: Most of the analytes investigated were not significantly affected by food intake. Six of them were influenced by breakfast or lunch: triglycerides, glucose, creatinine, C-peptide and insulin were significantly upregulated, whereas testosterone was downregulated. Fourteen parameters were more influenced by time of sampling than by meals: nine decreased during the day (total bilirubin, BNP, myoglobin, cortisol, TSH, C-telopeptide, prolactin, ACTH, uric acid) and two increased (white blood cells, neutrophils). Three parameters showed levels that were similar at 9:00 am and 5:00 pm but their lowest level at 12:30 pm (inorganic phosphorus, osteocalcin, PTH). CONCLUSIONS: Fasting is necessary for some laboratory tests. Clinicians should be aware of variations due to sampling time before ordering non-fasting tests, and in the subsequent interpretation of results.

Stability study of 81 analytes in human whole blood, in serum and in plasma.

OBJECTIVE: We studied the pre-analytical stability of 81 analytes based on the variables of delay before processing, storage as whole blood or serum/plasma, the storage temperature and the type of tube the sample was stored in. DESIGN AND METHODS: The mean difference between assays for samples from 10 subjects was calculated with the samples being kept under different storage conditions and for different times between sampling time and analysis: up to 24h for biochemistry, coagulation and hematology, and up to 72 h for hormonology. This difference was compared to the acceptable limits derived from the analytical and the intra individual biological variation. RESULTS: Most of the analytes investigated remained stable up to 24h under all storage conditions prior to centrifugation. However, some analytes were significantly affected either by delay, tube type or temperature, such as potassium, inorganic phosphorus, magnesium, LD, glucose, lactate, mean corpuscular volume, mean corpuscular hemoglobin, activated partial thromboplastin time, insulin, C-peptide, PTH, osteocalcin, C-telopeptide and ACTH. CONCLUSION: This study may be useful to help define acceptable delay times and storage conditions when a short time between sample collection and processing is not possible.

Influence of parathyroidectomy on mortality in hemodialysis patients: a prospective observational study.

BACKGROUND: In hemodialysis patients, the relationships between serum PTH and phosphorus levels and mortality are debated because both high and low turnover bone diseases increase the risk of vascular calcifications. Furthermore, the prevalence of hypoparathyroidism is increasing, and there is a fear that this state is associated with an increase in bone fractures. METHODS: We performed a cross-sectional study to determine the prevalence and the causes of hypoparathyroidism (defined as basal and post-hypocalcemic-challenge serum PTH levels < 55 pg/mL) in 97 patients undergoing chronic hemodialysis treatment in our unit. We then prospectively observed patients with low PTH levels (< 55 pg/mL, n = 26) and those with hyperparathyroidism defined as a PTH levels > 200 pg/mL (n = 25) during eight years for all causes of mortality and bone fractures. Kaplan-Meyer survival curves were adjusted for age and sex. RESULTS: Hypoparathyroidism was present in 30% of our patients. The main causes of hypoparathyroidism were parathyroidectomy (77%) and aluminium and iron overload. Survival did not differ between patients with hypoparathyroidism and hyperparathyroidism and between patients with serum phosphorus < or > 2 mmol/L. Parathyroidectomy was associated with better survival (p < 0.01). Similarly, incidence of bone fractures did not differ for the two groups. CONCLUSIONS: Parathyroidectomy is the main cause of hypoparathyroidism in hemodialysis patients and is associated with a lower mortality risk. This result suggests that a more aggressive treatment of secondary hyperparathyroidism could decrease mortality in this high-risk population.

Evaluation of new apolipoprotein C-II and apolipoprotein C-III automatized immunoturbidimetric kits.

BACKGROUND: Apolipoprotein C-II and apolipoprotein C-III play an important and complex role in plasma triglycerides metabolism, respectively, as inhibitor and activator of lipoprotein lipase. Thus, they appear to be suitable markers for clinical studies of triglyceride-rich lipoproteins and related cardiovascular risk. Our aim was to evaluate, for routine analysis, the accuracy to quantify these apolipoprotein in human sera. METHODS: Precision (intra- and inter-run), limit of detection and quantification, linearity, common interferents (lipids, haemoglobin, bilirubin) and reference intervals were determined according to guidelines of the French Society of Clinical Biology and ISO Norm 5725 specifications. RESULTS: Intra- and inter-run CVs were respectively less than 5.0% and 7.5%. Linearities extended from 10.8 mg/L to 112.9 mg/L for apolipoprotein C-II and from 31.8 mg/L to 375.5 mg/L for apolipoprotein C-III. Haemolysis (up to 227.6 micromol/L haemoglobin) and lipemia (up to 19.3 mmol/L triglycerides) do not interfere, contrary to bilirubin, which has a positive effect above 350 micromol/L. Comparison of methods shows good agreement between immunoturbidimetric and electro-immunodiffusion methods for measuring apolipoprotein C-III in 62 samples within a wide range (n = 62, r = 0.954, y = 3.81 x -14.4). CONCLUSION: This study shows the reliability of these kits for measuring apolipoprotein C-II and apolipoprotein C-III in human sera, and their suitability for routine analysis.

Anionic peptide factor/phosphatidylcholine particles promote the inhibition of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells.

OBJECTIVE: High-density lipoproteins (HDLs) have significant cardiovascular benefits by retarding the progression of atherosclerosis. One of the mechanisms is the inhibition by HDLs of the vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells. Our objective was to test the effect on VCAM-1 expression by the human umbilical vein endothelial cells (HUVEC) of a minor HDL2 and HDL3 apolipoprotein, the anionic peptide factor (APF). The peptide has previously been found to develop some beneficial effects against atherosclerosis, i.e. by promoting the cholesterol efflux from endothelial cells. METHODS: We examined the effects of two HDL apolipoproteins A-I and APF, either in presence or absence of phosphatidylcholines (PCs), or free PCs, on the expression of VCAM-1 by HUVEC. The cells were stimulated with either the tumor necrosis factor-alpha (TNFalpha, 500 pg/ml) or the calcium bound to heparin (10 microg Ca2+/ml, 50 microg heparin/ml). RESULTS: In the presence of TNFalpha, only the free PCs (0.25 and 1 mM) developed an inhibitory effect (up to 50%). In the absence of TNFalpha and in the presence of calcium bound to heparin, either the lipid-free APF (3.5 microM) or the APF/PC complexes (1:57 molar ratio) or the free PCs (0.25 mM) exhibited a substantial inhibitory effect (72, 71 and 42%, respectively). CONCLUSION: Our present findings suggest for the first time that one of the mechanisms of the antiatherogenic action of APF involves the inhibition of VCAM-1 expression by HUVEC. The peptide, through its phospholipid-binding and its calcium antagonist abilities, appears to confer on the HDLs a protective effect against the early cellular event of the inflammatory process.