Increasing Symptoms in Irritable Bowel Symptoms With Ingestion of Galacto-Oligosaccharides Are Mitigated by α-Galactosidase Treatment.

OBJECTIVES: Galacto-oligosaccharides (GOS) are dietary FODMAPs (fermentable carbohydrates) associated with triggering gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). This randomized, double-blind, placebo-controlled, cross-over trial aimed to assess whether oral α-galactosidase co-ingestion with foods high in GOS and low in other FODMAPs would reduce symptoms. METHODS: Patients meeting the Rome III criteria for IBS who were hydrogen-producers on breath testing were recruited. Participants were treated with full-dose (300 GALU (galactosidic units) α-galactosidase) and half-dose enzyme (150 GALU α-galactosidase), and placebo (glucose) in a random order with ≤14 days washout between arms. Following a 3-day low FODMAP run-in period, participants consumed provided diets high in GOS for a further 3-days. Gastrointestinal symptoms were measured daily using a 100 mm visual-analogue-scale, and breath samples taken hourly on the second last day with hydrogen content analysed as area-under-the-curve. RESULTS: Thirty-one patients with IBS (20 IBS-D, 4 IBS-C, 7 IBS-M) completed the study. The addition of high GOS foods resulted in a significant increase in overall symptoms with 21 patients exhibiting GOS-sensitivity (>10 mm increase for overall symptoms). Of those, full-dose enzyme reduced overall symptoms (median 24. 5(IQR 17.5-35.8) vs. 5.5(1.5-15.0) mm; P=0.006) and bloating (20.5(9.5-42.0) vs. 6.5(2.0-15.8); P=0.017). Breath hydrogen production was minimal with no differences seen between placebo and full-dose (P=0.597). CONCLUSIONS: Oral α-galactosidase taken with high GOS foods provides a clinically significant reduction in symptoms in GOS-sensitive individuals with IBS. This strategy can be translated into practice to improve tolerance to high GOS foods as an adjunct therapy to the low FODMAP diet.

Fermentable short chain carbohydrate (FODMAP) content of common plant-based foods and processed foods suitable for vegetarian- and vegan-based eating patterns.

BACKGROUND: The low FODMAP (fermentable, oligo-, di-, mono-saccharides and polyols) diet is an effective strategy to improve symptoms of irritable bowel syndrome. However, combining the low FODMAP diet with another dietary restriction such as vegetarianism/veganism is challenging. Greater knowledge about the FODMAP composition of plant-based foods and food processing practices common to vegetarian/vegan eating patterns would assist in the implementation of the diet in this patient population. The present study aimed to quantify the FODMAP content of plant-based foods common in vegetarian/vegan diets and to investigate whether food processing can impact FODMAP levels. METHODS: Total FODMAP content was quantified in 35 foods, including fructose-in-excess-of-glucose, lactose, sorbitol, mannitol, galacto-oligosaccharide and total fructan, using high-performance-liquid-chromatography and enzymatic assays. The effects of cooking, sprouting, pickling, fermentation, activation and canning on FODMAP content were assessed. The Monash University criteria to classify foods as low FODMAP was used. RESULTS: Of the 35 foods, 20 were classified as low FODMAP, including canned coconut milk (0.24 g serve-1 ), dulse (0.02 serve-1 ), nutritional yeast (0.01 serve-1 ), soy cheese (0.03 serve-1 ), tempeh (0.26 serve-1 ), wheat gluten (0.13 serve-1 ) and wheat grass (0.05 serve-1 ). No FODMAPs were detected in agar-agar, egg replacer, vegan egg yolk, kelp noodles and spirulina. Food processing techniques that produced the greatest reduction in FODMAP content included pickling and canning. CONCLUSIONS: The present study provides a greater FODMAP composition knowledge of plant-based foods that can now be applied to the dietetic management of vegetarians/vegans requiring a low FODMAP diet. Food processing lowered the FODMAP content of foods, thereby increasing options for patients following a low FODMAP diet.

Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption.

BACKGROUND: In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. METHODS: Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. RESULTS: For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h-1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. CONCLUSIONS: The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders.

Feminized behavior and brain gene expression in a novel mouse model of Klinefelter Syndrome.

Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy in men and is characterized by the presence of an additional X chromosome (XXY). In some Klinefelter males, certain traits may be feminized or shifted from the male-typical pattern towards a more female-typical one. Among them might be partner choice, one of the most sexually dimorphic traits in the animal kingdom. We investigated the extent of feminization in XXY male mice (XXYM) in partner preference and gene expression in the bed nucleus of the stria terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy model. We tested for partner preference using a three-chambered apparatus in which the test mouse was free to choose between stimulus animals of either sex. We found that partner preference in XXYM was feminized. These differences were likely due to interactions of the additional X chromosome with the Y. We also discovered genes that differed in expression in XXYM versus XYM. Some of these genes are feminized in their expression pattern. Lastly, we also identified genes that differed only between XXYM versus XYM and not XXM versus XYM. Genes that are both feminized and unique to XXYM versus XYM represent strong candidates for dissecting the molecular pathways responsible for phenotypes present in KS/XXYM but not XXM. In sum, our results demonstrated that investigating behavioral and molecular feminization in XXY males can provide crucial information about the pathophysiology of KS and may aid our understanding of sex differences in brain and behavior.

The genetics of sex differences in brain and behavior.

Biological differences between men and women contribute to many sex-specific illnesses and disorders. Historically, it was argued that such differences were largely, if not exclusively, due to gonadal hormone secretions. However, emerging research has shown that some differences are mediated by mechanisms other than the action of these hormone secretions and in particular by products of genes located on the X and Y chromosomes, which we refer to as direct genetic effects. This paper reviews the evidence for direct genetic effects in behavioral and brain sex differences. We highlight the 'four core genotypes' model and sex differences in the midbrain dopaminergic system, specifically focusing on the role of Sry. We also discuss novel research being done on unique populations including people attracted to the same sex and people with a cross-gender identity. As science continues to advance our understanding of biological sex differences, a new field is emerging that is aimed at better addressing the needs of both sexes: gender-based biology and medicine. Ultimately, the study of the biological basis for sex differences will improve healthcare for both men and women.

Nutritional profile of rodent diets impacts experimental reproducibility in microbiome preclinical research.

The lack of reproducibility of animal experimental results between laboratories, particularly in studies investigating the microbiota, has raised concern among the scientific community. Factors such as environment, stress and sex have been identified as contributors, whereas dietary composition has received less attention. This study firstly evaluated the use of commercially available rodent diets across research institutions, with 28 different diets reported by 45 survey respondents. Secondly, highly variable ingredient, FODMAP (Fermentable Oligo-, Di-, Mono-saccharides And Polyols) and gluten content was found between different commercially available rodent diets. Finally, 40 mice were randomized to four groups, each receiving a different commercially available rodent diet, and the dietary impact on cecal microbiota, short- and branched-chain fatty acid profiles was evaluated. The gut microbiota composition differed significantly between diets and sexes, with significantly different clusters in ß-diversity. Total BCFA were highest (p = 0.01) and SCFA were lowest (p = 0.03) in mice fed a diet lower in FODMAPs and gluten. These results suggest that nutritional composition of commercially available rodent diets impact gut microbiota profiles and fermentation patterns, with major implications for the reproducibility of results across laboratories. However, further studies are required to elucidate the specific dietary factors driving these changes.

Membrane curvature and surface area per lipid affect the conformation and oligomeric state of HIV-1 fusion peptide: a combined FTIR and MD simulation study.

Fourier-transformed infrared spectroscopy (FTIR) and molecular dynamics (MD) simulation results are presented to support our hypothesis that the conformation and the oligomeric state of the HIV-1 gp41 fusion domain or fusion peptide (gp41-FP) are determined by the membrane surface area per lipid (APL), which is affected by the membrane curvature. FTIR of the gp41-FP in the Aerosol-OT (AOT) reversed micellar system showed that as APL decreases from approximately 50 to 35 A2 by varying the AOT/water ratio, the FP changes from the monomeric alpha-helical to the oligomeric beta-sheet structure. MD simulations in POPE lipid bilayer systems showed that as the APL decreases by applying a negative surface tension, helical monomers start to unfold into turn-like structures. Furthermore, an increase in the applied lateral pressure during nonequilibrium MD simulations favored the formation of beta-sheet structure. These results provide better insight into the relationship between the structures of the gp41-FP and the membrane, which is essential in understanding the membrane fusion process. The implication of the results of this work on what is the fusogenic structure of the HIV-1 FP is discussed.

Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions.

BACKGROUND: Functional gastrointestinal symptoms in irritable bowel syndrome (IBS) and quiescent inflammatory bowel disease (IBD) cause significant morbidity and a reduction in quality of life. Multiple dietary therapies are now available to treat these symptoms, but supporting evidence for many is limited. In addition to a further need for studies demonstrating efficacy and mechanism of action of dietary therapies, the risk of nutritional inadequacy, alterations to the microbiome and changes in quality of life are key concerns requiring elucidation. Identifying predictors of response to dietary therapy is an important goal as management could be tailored to the individual to target specific dietary components, and thereby reduce the level of dietary restriction necessary. PURPOSE: This review discusses the available dietary therapies to treat symptoms in patients with IBS and patients with quiescent IBD suffering from IBS symptoms, with the aim to understand where current dietary evidence lies and how to move forward in dietary research in this field.

3D-printed components for quantum devices.

Recent advances in the preparation, control and measurement of atomic gases have led to new insights into the quantum world and unprecedented metrological sensitivities, e.g. in measuring gravitational forces and magnetic fields. The full potential of applying such capabilities to areas as diverse as biomedical imaging, non-invasive underground mapping, and GPS-free navigation can only be realised with the scalable production of efficient, robust and portable devices. We introduce additive manufacturing as a production technique of quantum device components with unrivalled design freedom and rapid prototyping. This provides a step change in efficiency, compactness and facilitates systems integration. As a demonstrator we present an ultrahigh vacuum compatible ultracold atom source dissipating less than ten milliwatts of electrical power during field generation to produce large samples of cold rubidium gases. This disruptive technology opens the door to drastically improved integrated structures, which will further reduce size and assembly complexity in scalable series manufacture of bespoke portable quantum devices.

Meso-scale defect evaluation of selective laser melting using spatially resolved acoustic spectroscopy.

Developments in additive manufacturing technology are serving to expand the potential applications. Critical developments are required in the supporting areas of measurement and in process inspection to achieve this. CM247LC is a nickel superalloy that is of interest for use in aerospace and civil power plants. However, it is difficult to process via selective laser melting (SLM) as it suffers from cracking during rapid cooling and solidification. This limits the viability of CM247LC parts created using SLM. To quantify part integrity, spatially resolved acoustic spectroscopy (SRAS) has been identified as a viable non-destructive evaluation technique. In this study, a combination of optical microscopy and SRAS was used to identify and classify the surface defects present in SLM-produced parts. By analysing the datasets and scan trajectories, it is possible to correlate morphological information with process parameters. Image processing was used to quantify porosity and cracking for bulk density measurement. Analysis of surface acoustic wave data showed that an error in manufacture in the form of an overscan occurred. Comparing areas affected by overscan with a bulk material, a change in defect density from 1.17% in the bulk material to 5.32% in the overscan regions was observed, highlighting the need to reduce overscan areas in manufacture.

Membrane structure of the human immunodeficiency virus gp41 fusion peptide by molecular dynamics simulation. II. The glycine mutants.

In this work, molecular dynamics (MD) simulation of the interaction of three mutants, G3V, G5V and G10V, of the human immunodeficiency virus (HIV) gp41 16-residue fusion peptide (FP) with an explicit palmitoyloleoylphosphatidyl-ethanolamine (POPE) lipid bilayer was performed. The goals of this work are to study the correlation of the fusogenic activity of the FPs with the mode of their interaction with the bilayer and to examine the roles of the many glycine residues in the FP in the fusion process. The results of this work corroborate the main conclusion of our earlier MD work of the WT FP and several mutants with polar substitution. These two studies provide correlation between the mode of insertion and the fusogenic activity of these peptides and support the hypothesis that an oblique insertion of the fusion domain of the viral protein is required for fusogenic activity. Inactive mutants interact with the bilayer by a surface-binding mode. The results of this work, combined with the results of our earlier work, show that, while the secondary structures of the wild-type FP and its mutants do not affect the fusogenic activities, the conformational flexibility appears to be an important factor. The active WT FP and its partially active mutants, G3V and G5V, all have significant conformational transitions at one of the glycine sites. They occur at Gly(5) in FP-wt, at Gly(10) in FP-G5V and at Gly(13) in FP-G3V. Thus, a glycine site in each of these active (or partially active) FPs provides conformational flexibility. On the other hand, the inactive mutants FP-G10V, FP-L9R and FP-V2E do not have any conformational transitions except at either terminus and thus possess no conformational flexibility. Thus, the results of this work support the suggestion that the role of glycine residues in the fusion domain is to provide the necessary conformational flexibility for fusion activity. The glycines also form a "glycine strip" in the FP that locates on one (the less hydrophobic) face of the helix (the "sided helix"). However, whether this "glycine strip" is disrupted or not does not seem to correlate with the retention of fusogenic activities. Finally, although the FLGFL (8-12) motif is absolutely conserved in the HIV fusion domain, a well-structured motif stabilized by hydrogen bonding does not appear to be required for activity. In fact, hydrogen bonding in this motif was found to be missing in FP-G3V and FP-G5V. Both of these mutants are partially active.

The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics determined by NMR spectroscopy.

The wild-type (wt) N-terminal 23-residue fusion peptide (FP) of the human immunodeficiency virus (HIV) fusion protein gp41 and its V2E mutant have been studied by nuclear magnetic resonance (NMR) spectroscopy in dodecylphosphocholine (DPC) micelles as membrane mimics. A number of NMR techniques have been used. Pulsed field-gradient diffusion measurements in DPC and in 4:1 DPC/sodium dodecylsulfate mixed micelles showed that there is no major difference between the partition coefficients of the fusogenic wt peptide and the V2E mutant in these micelles, indicating that there is no correlation between the activity of the fusion peptides and their membrane affinities. The nuclear Overhauser enhancement (NOE) patterns and the chemical shift index for these two peptides indicated that both FP are in an alpha helical conformation between the Ile4 to Leu12 or to Ala15 region. Simulated annealing showed that the helical region extends from Ile4 to Met19. The two FPs share similar conformational characteristics, indicating that the conformation of the FP is not an important factor determining its activity. The spin-label studies, utilizing spin labels 5- and 16-doxystearic acids in the DPC micelles, provided clear indication that the wt FP inserts its N-terminus into the micelles while the V2E mutant does not insert into the micelles. The conclusion from the spin-label results is corroborated by deuterium amide proton exchange experiments. The correlation between the oblique insertion of the FP and its fusogenic activity is in excellent agreement with results from our molecular dynamics simulation and from other previous studies.

High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men.

Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (>/=50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; P:=0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P:=0.043). Elevated Lp(a) levels (>/=30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P:<0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a).

Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes.

Asymmetric dimethylarginine (ADMA), a compound detectable in human plasma, is an endogenous inhibitor of NO synthase. Endothelial dysfunction is an early event in atherogenesis, and large-vessel atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Fifty patients with type 2 diabetes mellitus were studied at baseline and 5 hours after ingestion of a high-fat meal. Plasma ADMA measured by using high-performance liquid chromatography increased from 1.04+/-0.99 to 2.51+/-2.27 micromol/L (P:<0.0005). Brachial arterial vasodilation after reactive hyperemia, a NO-dependent function, measured by high-resolution ultrasound, decreased from 6.9+/-3.9% at baseline to 1.3+/-4.5% (P:<0.0001). These changes occurred in association with increased plasma levels of triglycerides and very low density lipoprotein triglycerides, with reduced low density lipoprotein cholesterol and high density lipoprotein cholesterol, and with no changes in total cholesterol. The increase in plasma ADMA in response to a high-fat meal was significantly and inversely related to the decrease in percent vasodilation. In 10 of the subjects studied with a similar protocol on another day, no significant changes in the brachial artery flow responses or in plasma ADMA were observed 5 hours after ingestion of a nonfat isocaloric meal. The data suggest that ADMA may contribute to abnormal blood flow responses and to atherogenesis in type 2 diabetics.

Association of hyperandrogenemia and hyperestrogenemia with type 2 diabetes in Hispanic postmenopausal women.

OBJECTIVE: Accumulating evidence suggests that hyperandrogenemia may be a risk factor for coronary heart disease (CHD) in women. The present study was carried out to test the hypothesis that hyperandrogenemia is associated with type 2 diabetes in women and thus may contribute to the increased risk of CHD in women with type 2 diabetes. RESEARCH DESIGN AND METHODS: Sex hormones, sex hormone-binding globulin (SHBG), and risk factors for CHD were measured in 20 postmenopausal women with type 2 diabetes and in 29 control subjects. All of the diabetic and control subjects were Hispanic women aged >55 years who were not taking hormone replacement therapy lipid-lowering drugs, or insulin and who were otherwise randomly chosen from a cohort of stroke-free subjects from the Northern Manhattan Stroke Study RESULTS: Mean age, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood pressure, and smoking were not significantly different between cases and control subjects, but waist-to-hip ratio (WHR) was significantly higher in the diabetic subjects (P = 0.01). The mean levels of free testosterone (FT) (P = 0.01), dehydroepiandrosterone sulfate (P<0.04), and estradiol (P = 0.01) (controlled for WHR) were significantly higher in the diabetic subjects; with the statistical outliers removed, the testosterone (P = 0.05) and androstenedione (P = 0.002) levels (controlled for WHR) were also significantly higher in the diabetic subjects. The mean levels of estrone, cortisol, and SHBG were not significantly different. The results were similar in the 10 diabetic subjects treated with diet only Significant positive correlations (controlled for age and BMI) were observed between FT or testosterone and cholesterol, LDL cholesterol, and blood pressure. CONCLUSIONS: Postmenopausal Hispanic women with type 2 diabetes had both hyperandrogenemia and hyperestrogenemia, and testosterone or FT correlated positively with risk factors for CHD. Hyperandrogenemia may be a link between diabetes and CHD in women.

An inverse method for determining the spatially resolved properties of viscoelastic-viscoplastic three-dimensional printed materials.

A method using experimental nanoindentation and inverse finite-element analysis (FEA) has been developed that enables the spatial variation of material constitutive properties to be accurately determined. The method was used to measure property variation in a three-dimensional printed (3DP) polymeric material. The accuracy of the method is dependent on the applicability of the constitutive model used in the inverse FEA, hence four potential material models: viscoelastic, viscoelastic-viscoplastic, nonlinear viscoelastic and nonlinear viscoelastic-viscoplastic were evaluated, with the latter enabling the best fit to experimental data. Significant changes in material properties were seen in the depth direction of the 3DP sample, which could be linked to the degree of cross-linking within the material, a feature inherent in a UV-cured layer-by-layer construction method. It is proposed that the method is a powerful tool in the analysis of manufacturing processes with potential spatial property variation that will also enable the accurate prediction of final manufactured part performance.

Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study.

Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0 +/- 12.1 years; 32% women) presenting with AIS (evaluated within 9.7 +/- 12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225 +/- 57.6, 154 +/- 56.0, 40 +/- 10.4, 181 +/- 93.7, 52 +/- 28.6, 130 +/- 24.6, and 141 +/- 46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.

Molecular dynamics simulations of adrenocorticotropin (1-24) peptide in a solvated dodecylphosphocholine (DPC) micelle and in a dimyistoylphosphatidylcholine (DMPC) bilayer.

The structure and interactions of the 1-24 fragment of the adrenocorticotropin hormone, ACTH (1-24), with membrane have been studied by molecular dynamics (MD) simulation in an NPT ensembles in two explicit membrane mimics, a dodecylphosphocholine (DPC) micelle and a dimyristoylphosphatidylcholine (DMPC) bilayer. The starting configuration of the peptide/lipid systems had the 1-10 segment of the peptide lying on the surface of the model membrane, the same as the equilibrated structure (by MD) of ACTH (1-10) in a DPC micelle. The simulations showed that the peptide adopts the surface-binding mode and essentially the same structure in both systems. Thus the results of this work lend support to the assumption that micelles are reasonable mimics for biological membranes for the study of peptide binding. The 1-10 segment is slightly tilted from the parallel orientation to the interface and interacts strongly with the membrane surface while the more polar 11-24 segment shows little tendency to interact with the membrane surface, preferring to reside primarily in the aqueous phase. Furthermore, the 1-10 segment of the peptide binds to the DPC micelle in essentially the same way as ACTH (1-10). Thus the MD results are in excellent agreement with the model of interaction of ACTH (1-24) with membrane derived from NMR experiments. The secondary structure and the hydration of the peptide and the interactions of specific residues with the lipid head groups have also been analyzed.

Survival of cornual (interstitial) pregnancy.

We report a case of a singleton cornual (interstitial) pregnancy following spontaneous conception in a primigravida with no risk factors for ectopic pregnancy. She presented at 30 weeks gestation with haemoperitoneum, due to a small rupture on the posterior surface of the cornual pregnancy. At laparotomy, an incision was made in the cornu, the baby was delivered and survived after spending 39 days in a special care baby unit.

Diabetes and dyslipidemia.

Numerous prospective cohort studies have indicated that diabetes mellitus (DM), particularly type-2 DM (the type of diabetes associated with insulin resistance that usually strikes adults), is associated with a 3-4-fold increase in risk for coronary heart disease (CHD) [1-3]. The increase in risk is particularly evident in younger-age groups, and in women: females with type-2 DM appear to lose a great deal of the protection that characterizes non-diabetic females. Furthermore, patients with DM have a 50% greater in-hospital mortality, and a 2-fold increased rate of death within 2 years of surviving a myocardial infarction. Overall, CHD is the leading cause of death in individuals with DM who are >35 years old. Although a significant portion of this increased risk is associated with the presence of well-characterized risk factors for CHD, a significant proportion remains unexplained. Patients with DM, particularly those with type-2 DM, have abnormal plasma lipid and lipoprotein concentrations that are less commonly present in non-diabetics [4-6]. Patients with poorly controlled type-1 DM can also have a dyslipidemic pattern, but, in this review, we will focus on the dyslipidemia seen commonly in patients with type-2 DM. In particular, we will describe the pathophysiology underlying the increase in plasma very low-density lipoprotein triglyceride levels, the reductions in plasma high-density lipoprotein cholesterol levels, and the abnormal, small, dense low-density lipoproteins that are the central components of diabetic dyslipidemia. The dyslipidemia of DM clearly adds significantly to the high risk for CHD in this group, and must be treated aggressively with diet, weight loss and lipid-altering medications. Combinations of lipid-altering medications, particularly statins and fibrates, can markedly change plasma lipid levels, often bringing them all into the normal range.