A cytotoxic flavonol glycoside from Melaleuca leucadendra leaves extract with immunostimulant activity.

Leaves of Melaleuca leucadendra contain the novel flavonol glycoside, myricetin 3-O-ß-4C1-galactopyranuronoid. In addition, known fifteen phenolics were identified. All isolates are characterized for the first time from this plant. Structures were established by conventional methods and confirmed by spectral methods of analysis, including one and two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D-NMR) and high resolution electro-spray ionization mass spectrometry (HRESIMS), as well. Assessment of some immunological and biological efficacy, of the extract in combination with a parallel cytotoxicity evaluation, using the method of cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) technique was carried out. Besides, evaluation of the antioxidant effectiveness, using the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the oxygen radical absorption capacity (ORAC) methods was performed. In addition, the cytotoxicity against liver (Huh-7), breast (MCF-7) and prostate (PC-3) cancers using the neutral red assay (NRU) technique for the extract and the new flavonol glycoside also, was assessed.

Prediction of organ-specific complications following abdominal aortic aneurysm repair using cardiopulmonary exercise testing.

This study aimed at assessing whether measures of aerobic fitness can predict postoperative cardiac and pulmonary complications, 30-day mortality and length of hospital stay following elective abdominal aortic aneurysm repair. We prospectively collected cardiopulmonary exercise testing data over two years for 130 patients. Upon multivariate analysis, a decreased anaerobic threshold (OR (95% CI) 0.55 (0.37-0.84); p = 0.005) and open repair (OR (95% CI) 6.99 (1.56-31.48); p = 0.011) were associated with cardiac complications. Similarly, an increased ventilatory equivalent for carbon dioxide (OR (95% CI) 1.18 (1.05-1.33); p = 0.005) and open repair (OR (95% CI) 14.29 (3.24-62.90); p < 0.001) were associated with pulmonary complications. Patients who had an endovascular repair had shorter hospital and critical care lengths of stay (p < 0.001). Measures of fitness were not associated with 30-day mortality or length of hospital stay. Cardiopulmonary exercise testing variables, therefore, seem to predict different postoperative complications following abdominal aortic aneurysm repair, which adds value to their routine use in risk stratification and optimisation of peri-operative care.

Ruptured AAA: suitability for endovascular repair is associated with lower mortality following open repair.

OBJECTIVES: Perioperative mortality of open repair of ruptured abdominal aortic aneurysms (rAAA) remains unacceptably high: 30-day mortality ≈ 40 %. This study aimed to assess, quantify, and determine the consequences of anatomic suitability for endovascular repair of rAAA. DESIGN: A retrospective analysis of the prospectively maintained database identified patients with rAAA. METHODS: Preoperative CT scans were assessed for anatomic suitability for emergency EVAR and precluding factors recorded. Demographic information was collected and analysed for all patients. RESULTS: A total of 141 patients underwent open surgical repair of rAAA. Forty-six patients had preoperative CT scans suitable for reconstruction. Morphological measurements indicated that 41 % would have been anatomically suitable for EVAR. Suitability was associated with lower mortality rates than unsuitability: 0, 11, and 20 % (24 h, 30 days, and 1 year respectively) versus 11, 33, and 59 % (statistically significant at 1 year; p = 0.02). The groups were comparable excepting diabetes incidence, which was higher in those suitable for EVAR (p = 0.003). CONCLUSIONS: A minority of patients with ruptured AAA are anatomically suitable for EVAR. Anatomical suitability appears to identify patients at low risk from open surgery. Whether this is due to technically less demanding open surgery is unknown. This may be resolved by the IMPROVE trial results, which are eagerly awaited.

Glycine alleviates liver injury induced by deficiency in methionine and or choline in rats.

OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is an advanced stage of non-alcoholic fatty liver disease (NAFLD) from steatosis. Methionine and choline are important amino acids play a key role in many cellular functions. Glycine is a non-essential amino acid having multiple roles in many reactions. This study aimed to investigate liver damage induced by feeding male albino rats either methionine deficient (MD), choline deficient (CD), or MCD diets. And to clarify the alleviatory effect of dietary glycine supplementation (5%) on reduced complications caused by feeding each of the deficient diets. MATERIAL AND METHODS: Nutritional status, liver functions, lipids profile, hepatic oxidative stress, hepatic antioxidant enzymes, tumor markers and hepatic fatty acid transport protein gene were assessed. RESULTS: Rats fed with either MD or MCD diet had less body weight gain unlike rats fed the CD diet. Liver injury was detected in deficient groups by elevating plasma ALT, AST, ALP, total and direct bilirubin, albumin and protein levels. Lipid accumulation was more prominent in rats fed the MCD or CD diet than in those fed the MD diet. Fatty acid transport protein (FATP) was significantly elevated in the different glycine supplemented groups. CONCLUSION: Oral administration of glycine confers a significant protective effect by optimizing all the assessed parameters and gene expression.

Urethrographic examinations: Patient and staff exposures and associated radiobiological risks.

Medical exposure of the general population due to radiological investigations is the foremost source of all artificial ionising radiation. Here, we focus on a particular diagnostic radiological procedure, as only limited data are published with regard to radiation measurements during urethrograpic imaging. Specifically, this work seeks to estimate patient and occupational effective doses during urethrographic procedures at three radiology hospitals. Both staff and patient X-ray exposure levels were calculated in terms of entrance surface air kerma (ESAK), obtained by means of lithium fluoride thermoluminescent dosimeters (TLD-100(LiF:Mg:Cu.P)) for 243 urethrographic examinations. Patient radiation effective doses per procedure were estimated using conversion factors obtained from the use of Public Health England computer software. In units of mGy, the median and range of ESAK per examination were found to be 10.8 (3.6-26.2), 7.0 (0.2-32.3), and 24.3 (9.0-32.0) in Hospitals A, B, and C, respectively. The overall mean and range of staff doses (in µGy) were found to be 310 (4.0-1750) per procedure. With the exception of hospital C, the present evaluations of radiation dose have been found to be similar to those of previously published research. The wide range of patient and staff doses illustrate the need for radiation dose optimisation.

Okadaic acid mimics a nuclear component required for cyclin B-cdc2 kinase microinjection to drive starfish oocytes into M phase.

G2-arrested oocytes contain cdc2 kinase as an inactive cyclin B-cdc2 complex. When a small amount of highly purified and active cdc2 kinase, prepared from starfish oocytes at first meiotic metaphase, is microinjected into Xenopus oocytes, it induces activation of the inactive endogenous complex and, as a consequence, drives the recipient oocytes into M phase. In contrast, the microinjected kinase undergoes rapid inactivation in starfish oocytes, which remain arrested at G2. Endogenous cdc2 kinase becomes activated in both nucleated and enucleated starfish oocytes injected with cytoplasm taken from maturing oocytes at the time of nuclear envelope breakdown, but only cytoplasm taken from nucleated oocytes becomes able thereafter to release second recipient oocytes from G2 arrest, and thus contains M phase-promoting factor (MPF) activity. Both nucleated and enucleated starfish oocytes produce MPF activity when type 2A phosphatase is blocked by okadaic acid. If type 2A phosphatase is only partially inhibited, neither nucleated nor enucleated oocytes produce MPF activity, although both do so if purified cdc2 kinase is subsequently injected as a primer to activate the endogenous kinase. The nucleus of starfish oocytes contains an inhibitor of type 2A phosphatase, but neither active nor inactive cdc2 kinase. Microinjection of the content of a nucleus into the cytoplasm of G2-arrested starfish oocytes activates endogenous cdc2 kinase, produces MPF activity, and drives the recipient oocytes into M phase. Together, these results show that the MPF amplification loop is controlled, both positively and negatively, by cdc2 kinase and type 2A phosphatase, respectively. Activation of the MPF amplification loop in starfish requires a nuclear component to inhibit type 2A phosphatase in cytoplasm.

A nuclear factor required for specific translation of cyclin B may control the timing of first meiotic cleavage in starfish oocytes.

In most animals, the rate of cyclin B synthesis increases after nuclear envelope breakdown during the first meiotic cell cycle. We have found that cyclin B-cdc2 kinase activity drops earlier in emetine-treated than in control starfish oocytes, although the protein synthesis inhibitor does not activate the cyclin degradation pathway prematurely. Moreover, protein synthesis is required to prevent meiotic cleavage to occur prematurely, sometimes before chromosomes have segregated on the metaphase plate. In normal conditions, increased synthesis of cyclin B after germinal vesicle breakdown (GVBD) balances cyclin degradation and increases the time required for cyclin B-cdc2 kinase to drop below the level that inhibits cleavage. Taken together, these results point to cyclin B as a possible candidate that could explain the need for increased protein synthesis during meiosis I. Although direct experimental evidence was not provided in the present work, cyclin B synthesis after GVBD may be important for correct segregation of homologous chromosomes at the end of first meiotic metaphase, as shown by a variety of cytological disorders that accompany premature cleavage. Although the overall stimulation of protein synthesis because of cdc2 kinase activation is still observed in oocytes from which the germinal vesicle has been removed before hormonal stimulation, the main increase of cyclin B synthesis normally observed after germinal vesicle breakdown is suppressed. The nuclear factor required for specific translation of cyclin B after GVBD is not cyclin B mRNA, as shown by using a highly sensitive reverse transcription followed by polymerase chain reaction procedure that failed to detect any cyclin B mRNA in isolated germinal vesicles.

Phenolics from extracts of Brahea armata with inhibitory effect against 5alpha-reductase type-II.

Fractions of the aqueous alcohol extracts of the rind and kernel of Brahea aramata fruits have been investigated for their activity against 5alpha-reductase type II, which is expressed predominantly in the prostate. This isozyme represents a major target for drugs against benign prostate hyperplasia (BPH) and prostate cancer. Also, a structural analysis of the phytophenolics, present in both aqueous alcohol extracts as the major constituents, has led to the isolation of five phenolics, including the new natural product, 4',6'-dimethoxy beta,4,2'-trihydroxy chalcone from the rind extract and three phenolics, including the new natural product, 1-p-hydroxybenzoyl glycerol from the kernel extract. All structures were confirmed by ESI-MS and NMR analysis.

Neutral lipid biosynthesis in Mycobacterium smegmatis.

The biosynthesis of neutral lipids in Mycobacterium smegmatis was studied using cell free extracts. Maximum neutral lipid production was obtained when the reaction mixture (400 microliter) consisted of 0.25 M potassium phosphate buffer (pH 7.5), 0.125 mM oleoyl-CoA, 3.75 mM sn-glycerol-3-P, 10 mM MgCl2 and 1.85 mg bovine serum albumin. No magnesium dependency for the acylation of sn-glycerol-3-P was observed. A slight stabilizing effect seemed to occur due to this ion. The enzyme phosphatidate phosphohydrolase, on the other hand, was shown to be magnesium dependent. The activity of this enzyme also appeared to be stimulated by high concentration (0.75 to 1.25 mM) of ATP which enhanced lipid formation at all concentrations tested (0.25 to 3.75 mM). A heat-stable protective factor having a molecular weight less than 16 000 which caused a stimulatory effect on sn-glycerol 3-phosphate acyltransferase activity was found in the cell-free extracts. Preliminary experiments suggest that the factor might be polysaccharide in nature.

Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis.

The possible causes of the enhanced risk for coronary heart disease (CHD) were examined in morbidly obese women with normoglycemia, impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) before and after gastric bypass surgery. Compared with age-matched lean women, plasma lipid and apolipoprotein concentrations of the obese women before surgery favored atherogenesis. The risk for CHD may further be exacerbated in the IGT and NIDDM groups by the prevalence of smaller and denser low-density-lipoprotein (LDL) particles. LDL size correlated negatively with plasma insulin levels independent of triglyceride levels, age, or body mass index (BMI). After surgery, BMI, plasma insulin, and triglyceride levels decreased, but LDL size increased, and LDL density decreased. Neither cholesterol nor LDL cholesterol levels were affected after surgery, but high-density-lipoprotein cholesterol was increased in all patients after surgery. Although the mechanisms underlying the changes in the properties of LDL could not be determined from this study, these changes appear to be of benefit in reducing CHD risk in these patients.

Coronary heart disease risk factors in morbidly obese women with normal glucose tolerance.

OBJECTIVE--To examine if the risk for CHD increases progressively with increases in the BMI of normoglycemic, hyperinsulinemic, morbidly obese women (BMI > or = 35 kg/m2). RESEARCH DESIGN AND METHODS--Insulin sensitivity was evaluated by calculating an ISI following an OGTT. There was a significant linear relationship between ISI and BMI fitted by two straight lines intersecting at a point corresponding to a BMI of 29.7 +/- 1.5 kg/m2. Significant linear relationships between insulin sensitivity and BMI were obtained below and above this breakpoint. Similarly, a breakpoint for the relation between dBP and BMI corresponding to a BMI > or = 33.7 +/- 3.4 kg/m2 was obtained. Significant linear relationships between BMI and plasma fasting glucose, triglyceride, cholesterol, HDL cholesterol, sBP, or dBP were not observed in the women with a BMI > 35 kg/m2. RESULTS--Compared with lean (BMI < 27) women of similar age, the morbidly obese patients appear to be at a higher risk for CHD. This is suggested by statistically significant increases in fasting insulin (mean +/- SD; 187 +/- 137 vs. 64.2 +/- 16.2 pM) and triglyceride levels (128 +/- 78.1 vs. 73 +/- 25 mg/dl), sBP (132 +/- 114 vs. 104 +/- 15.8) and dBP (84 +/- 72 vs. 67 +/- 2.1 mmHg), and decreases in HDL cholesterol (1.03 +/- 0.44 vs. 1.29 +/- 0.82 mM) and apo A-I (91 +/- 55 vs. 122 +/- 35 mg/dl) concentrations. CONCLUSIONS--It appears that there may be a threshold of body mass up to which insulin sensitivity is associated with CHD risk. Above this threshold, there does not appear to be a progressive increase in the risk factors for CHD with increases in BMI.

Measurement of patient radiation doses in certain urography procedures.

Patients are exposed to significant radiation doses during diagnostic and interventional urologic procedures. This study aimed to measure patient entrance surface air kerma (ESAK) and to estimate the effective dose during intravenous urography (IVU), extracorporeal shock-wave lithotripsy (ESWL), and ascending urethogram (ASU) procedures. ESAK was measured in patients using calibrated thermo luminance dosimeters, GR200A). Effective doses (E) were calculated using the National Radiological Protection Board (NRPB) software. A total of 179 procedures were investigated. 27.9 % of the patients underwent IVU procedures, 27.9 % underwent ESWL procedures and 44.2 % underwent ASU procedures. The mean ESAK was 2.1, 4.18 and 4.9 mGy for IVU, ESWL, and ASU procedures, respectively. Differences in patient ESAK for the same procedure were observed. The mean ESAK values were comparable with those in previous studies.

Impact of the nature and concentration of plasticizers on the ability of PVC to sorb drug.

The sorption of a drug by an infusion set may dramatically reduce the drug delivery efficiency. In this paper, we investigated how the drug sorption, in static conditions, is affected by the plasticizer's nature and ratio in the case of plasticized PVC, one of the most common material for infusion set tubing. Within the study, the drug concentration in diazepam solutions was studied after contact with PVC films containing different amounts of DEHP, DEHT, TOTM and DINCH® plasticizers. Moreover the partition coefficients between material and water were calculated. The drug sorption levels were equivalent for the different plasticizers and there was a plasticizer ratio for which the drug uptake was enhanced. As a consequence, the amount of sorbed drug might not be only linked to the amount of plasticizer in the film and to the solubility of the drug in the plasticizer alone: it must probably depend on specific interactions between plasticizer and PVC.

Surgical treatment of obesity and its effect on diabetes: 10-y follow-up.

Since 1980 we have performed the identical Greenville gastric bypass (GGB) procedure on 479 morbidly obese patients with an acceptable morbidity and a mortality rate of 1.2%. The weight loss in the series was well maintained over the follow-up period of 10 y. The GGB can control non-insulin-dependent diabetes mellitus (NIDDM) in most patients. The group of 479 patients included 101 (21%) with NIDDM and another 62 (13%) who were glucose impaired. Of these 163 individuals, 141 reverted to normal and only 22 (5%) remained with inadequate control of their carbohydrate metabolism. Those patients who were older or whose diabetes was of longer duration were less likely to revert to normal values. The gastric bypass operation is an effective approach for the treatment of morbid obesity. Along with its control of weight, the operation also controls the hyperglycemia, hyperinsulinemia, and insulin resistance of the majority of patients with either glucose impairment or frank NIDDM.

Low density lipoprotein interaction with artery derived proteoglycan: the influence of LDL particle size and the relationship to atherosclerosis susceptibility.

An in vitro binding system was used to determine whether increases in LDL particle size and altered LDL chemical composition accompanying increased plasma cholesterol concentrations result in greater association of LDL with artery proteoglycan (PG) and whether the binding is related to atherosclerosis. LDL isolated from hypercholesterolemic atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons was complexed to purified White Carneau pigeon aorta-derived high molecular weight PG under conditions whereby PG monomers were saturated. Using LDL of molecular weight greater than 5.0 x 10(6) daltons from both pigeon breeds, an inverse correlation between LDL size and the number of LDL particles bound per micrograms PG was demonstrated (r = 0.87, P less than 0.01). This relationship was attributed to the increased size of the LDL particle rather than any modification in chemical composition known to occur when LDL size increases, suggesting the major effect was attributed to steric hindrance. White Carneau pigeons with high molecular weight LDL had more severe atherosclerosis and the PG-LDL complexes contained excess cholesterol but no relationship was seen between atherosclerosis and number of LDL complexed. In animals with LDL between 3.6 x 10(6) and 4.8 x 10(6) daltons, considerable variability in PG binding was apparent, but this also was not related to LDL chemical composition. In this group of pigeons, which were all White Carneau, the positive relationship of PG-LDL binding and aorta cholesterol concentration was significant (r = 0.67, P less than 0.05). These results suggest that factors other than chemical composition (perhaps surface charge or apoprotein conformation changes) influence PG-LDL binding and that the assessment of PG-LDL binding is useful in predicting atherosclerosis in animals that do not respond to hypercholesterolemia by increasing LDL size.

Plasma cholesteryl ester transfer protein activity is not linked to insulin sensitivity.

Plasma cholesteryl ester transfer protein (CETP) activity has been reported to decline during a hyperinsulinemic-euglycemic clamp. It has been suggested that this suppressive effect of acute hyperinsulinemia is linked to whole body insulin sensitivity, and that the insulin resistance that accompanies obesity leads to high plasma CETP activity found in obese subjects. In the present study, we used 2 experimental approaches to examine the putative link between CETP and insulin action. First, we examined if the clamp-induced suppression of plasma CETP activity is linked to whole body insulin sensitivity. Plasma CETP activity was measured at the beginning and end of a 2-hour hyperinsulinemic-euglycemic clamp in 18 nondiabetic individuals before and after an exercise training regimen that improved insulin sensitivity without weight loss. CETP activity decreased in response to the clamp procedure in 16 of 18 subjects, and on average, by 9% (P <.001). While training decreased plasma CETP activity (10%, P <.05), the improvement in insulin sensitivity had no statistical effect on the clamp-induced suppression of plasma CETP activity (training*clamp, P =.26). Second, we examined if insulin resistance is associated with an elevation in fasting plasma CETP activity when the influence of adiposity and diabetes were negated. Plasma CETP activity was measured in 41 women (12 insulin-sensitive lean; 8 insulin-resistant lean; 10 insulin-sensitive obese; 11 insulin-resistant obese). The level of insulin sensitivity had no significant effect on fasting plasma CETP activity, but CETP levels were 25% higher in obese subjects (P <.01). Thus, neither experimental approach provided evidence that plasma CETP levels are linked to insulin and insulin sensitivity. These data suggest that the elevated CETP activity found in obese patients is less associated with hyperinsulinemia and the accompanying insulin resistance, but rather is more related to some other metabolic complication of obesity.

Role of female sex steroids in regulating cholesteryl ester transfer protein in transgenic mice.

The role of sex steroids in the regulation of cholesteryl ester transfer protein (CETP) was examined in the following groups of female transgenic mice carrying the human CETP gene: (1) normal, (2) ovariectomized, (3) ovariectomized and treated with estrogen; (4) ovariectomized and treated with progesterone; (5) ovariectomized and treated with both hormones, and (6) ovariectomized and treated with tamoxifen. CETP activity was measured in the plasma, and in the particulate and the soluble fractions of liver, muscle, and adipose tissue. Human CETP specific activity was determined by taking the difference of cholesterol ester transfer in the presence and absence of an antibody (TP2) against human CETP Ovariectomy reduced hormone levels, but did not completely abolish them from the circulation. Plasma CETP activity was significantly reduced in the tamoxifen group. There were significant reductions in CETP in liver homogenate and the soluble fraction, as well as in the particulate fraction of adipose with ovariectomy. Hormone replacement did not restore CETP activity in either the plasma or the tissues. Tamoxifin treatment resulted in a decrease in CETP activity in both fractions of liver, but had no effect on adipose. In the soluble fraction of adipose tissue and both fractions of muscle, only trace CETP activity was detected. We conclude that (1) minimal amounts of sex steroid hormones may be sufficient to affect CETP expression; (2) the effects of sex steroid hormones vary among tissues; and (3) in addition to the sex steroids, factor(s) from the ovary are needed for the full expression of CETP in this animal model.

Effects of oral combined hormone replacement therapy on plasma lipids and lipoproteins.

Hormone replacement therapy has been shown to decrease the risk of coronary heart disease (CHD) in menopausal women. In this cross-sectional study, we addressed the following question: What effects would combined oral hormone replacement therapy have on plasma lipid and lipoprotein profiles independent of the other known CHD risk factors? We analyzed the plasma lipoproteins of two groups of menopausal women who were randomly selected from a large database of individuals. One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA) for at least 6 months (HRT). The two groups were not different in age, body weight, percent body fat, body mass index (BMI), waist to hip ratio, blood pressure, or insulin and glucose levels. High-density lipoprotein (HDL)-cholesterol was significantly higher (P < .05) in the HRT group. The total cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3 and H4) in HRT (P < .05), which are considered antiatherogenic. No differences were seen in the cholesterol concentration or size of low-density lipoprotein (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the combined estrogen and progesterone treatment leads to beneficial effects on plasma lipoproteins. The beneficial effects include (1) increases in HDL-cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation distribution, and (3) increases in apo A-1 levels and LCAT activity, which indicate an improvement in reverse cholesterol transport.

Alterations in low-density lipoproteins in subjects with abdominal adiposity.

Abdominal adiposity, as indexed by the waist to hip girth ratio (WHR), has been associated with increased risk and incidence of coronary heart disease (CHD). The purpose of this study was to determine if this enhanced risk is related to alterations in the structure of low density lipoproteins (LDL). LDL were isolated from nine nonobese men with an average WHR of 1.046 and nine nonobese men with a WHR of 0.94, who were matched on age (45.6 +/- 2.7 v 47.7 +/- 2.3 mean +/- SEM) percent body fat (26.5 +/- 0.5 v 26.1 +/- 0.9), and body mass index (27.3 +/- 0.6 v 26.3 +/- 0.6). The average molecular weight of LDL from the subjects with a high WHR was lower than that of subjects with low WHR (2.70 v 3.02 x 10(6) d), the average hydrated density higher (1.050 v 1.040 g/mL), and the mobility (Rf) on 2% to 16% polyacrylamide gradient gel electrophoresis higher. Subfractionation by equilibrium density ultracentrifugation showed that the LDL of subjects with a high WHR was predominantly in the heavy density range (1.038 to 1.048 g/mL) compared with the LDL of subjects with low WHR, which was in the lighter density range (1.030 to 1.040 g/mL). Chemical analysis of the subfractions showed that the peak density fractions of LDL of subjects with a high WHR had a lower cholesterol to protein ratio than the peak density fractions of LDL of subjects with low WHR. Electron microscopy of these peak density fractions showed that LDL of subjects with high WHR was smaller than that of subjects with low WHR. These characteristics of LDL of subjects with abdominal adiposity closely resemble the properties of LDL of patients with documented CHD. It is concluded that the increased risk of CHD associated with abdominal adiposity may be due in part to the alterations in LDL characteristics, and that these alterations in LDL are independent of the degree of obesity.

Influence of morbid obesity and non-insulin-dependent diabetes mellitus on high-density lipoprotein composition and subpopulation distribution.

The chemical composition, subpopulation distribution and peak hydrated density of high-density lipoprotein (HDL) were examined in 18 morbidly obese women with either normal glucose tolerance or with non-insulin-dependent diabetes mellitus (NIDDM), and in 15 age-matched lean control subjects. Similar measurements were made in the morbidly obese subjects after gastric bypass surgery for weight loss. In the diabetic group, HDL was relatively protein-enriched and cholesterol- and cholesterol ester-poor compared with the lean controls. The same trend was seen in the nondiabetic group, although the cholesterol ester difference was not significant. In both cases, both electrophoretic and density gradient analysis showed that plasma HDL contained more of the HDL3 and less of the HDL2 subfractions than that for the lean controls. Following surgery in the diabetic group, the protein percentage of HDL decreased, and that of cholesterol ester increased; for the nondiabetic group, the protein decreased and phospholipid increased. In the diabetic group, a shift of the electrophoretic HDL subpopulation distribution toward more HDL2 accompanied these changes. Average hydrated peak density of HDL shifted from the HDL3 to the HDL2 range for the diabetic group following surgery; for the nondiabetic group the peak density also decreased but still remained within the HDL3 range. In all cases, the differences seen were more pronounced among the diabetic patients. These changes in the properties of HDL after gastric bypass surgery may favorably influence the risk for coronary heart disease usually associated with diabetes.