Effect of obesity on gastrointestinal transit, pressure and pH using a wireless motility capsule.

BACKGROUND: Despite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development. AIM: To investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH. MATERIAL AND METHODS: An exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed). RESULTS: Food intake slowed gastric emptying in both groups (both P < 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements. CONCLUSION: Obesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.

Thermionic cooling devices based on resonant-tunneling AlGaAs/GaAs heterostructure.

We study by means of full quantum simulations the operating principle and performance of a semiconductor heterostructure refrigerator combining resonant tunneling filtering and thermionic emission. Our model takes into account the coupling between the electric and thermal currents by self-consistently solving the transport equations within the non-equilibrium Green's function framework and the heat equation. We show that the device can achieve relatively high cooling power values, while in the considered implementation, the maximum lattice temperature drop is severely limited by the thermal conductivity of the constituting materials. In such an out-of-equilibrium structure, we then emphasize the significant deviation of the phonon temperature from its electronic counterpart which can vary over several hundred Kelvin. The interplay between those two temperatures and the impact on the electrochemical potential is also discussed. Finally, viable options toward an optimization of the device are proposed.

Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger.

OBJECTIVE: Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. DESIGN: Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. RESULTS: Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. CONCLUSIONS: Motilin may be an important regulator involved in the pathogenesis of obesity.

Low cytochrome oxidase 4I1 links mitochondrial dysfunction to obesity and type 2 diabetes in humans and mice.

OBJECTIVES: Cytochrome oxidase (COX) dysfunction is associated with mitochondrial oxidative stress. We determined the association between COX expression, obesity and type 2 diabetes. SUBJECTS/METHODS: COX4I1 and COX10 genes were measured in monocytes of 24 lean controls, 31 glucose-tolerant and 67 diabetic obese patients, and 17 morbidly obese patients before and after bariatric surgery. We investigated the effect of caloric restriction and peroxisome proliferator-activated receptor (PPAR) agonist treatment on Cox in obese diabetic mice, and that of diet-induced insulin resistance in Streptozotocin-treated mice. RESULTS: Low COX4I1 was associated with type 2 diabetes in obese patients, adjusting for age, gender, smoking, interleukin-6 and high-sensitivity C-reactive protein, all related to metabolic syndrome (MetS; odds ratio: 6.1, 95% confidence interval: 2.3-16). In contrast, COX10 was low in glucose-tolerant and diabetic obese patients. In morbidly obese patients, COX4I1 was lower in visceral adipose tissue collected at bariatric surgery. In their monocytes, COX4I1 decreased after bariatric surgery, and low COX4I1 at 4 months was associated with MetS at 7 years. In leptin-deficient obese diabetic mice, Cox4i1 was low in white visceral adipose tissue (n=13; P<0.001) compared with age-matched lean mice (n=10). PPARγ-agonist treatment (n=13), but not caloric restriction (n=11), increased Cox4i1 (P<0.001). Increase in Cox4i1 depended on the increase in glucose transporter 4 (Glut4) expression and insulin sensitivity, independent of the increase in blood adiponectin. In streptozotocin-treated mice (three groups of seven mice, diet-induced insulin resistance decreased Cox4i1 and Glut4 (P<0.001 for both). CONCLUSION: COX4I1 depression is related to insulin resistance and type 2 diabetes in obesity. In peripheral blood monocytes, it may be a diagnostically useful biomarker.

A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome.

BACKGROUND: Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and delayed hypoglycemia (HG). Treatment is based on dietary measures and somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. METHODS: Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing (OGTT), abdominal ultrasound, and dumping symptom severity score (DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 µg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying (GE) were obtained. KEY RESULTS: Baseline OGTT was pathological in all patients based on PR (n = 5), HT (n = 1) or HG (n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. CONCLUSIONS & INFERENCES: Pasireotide affects pathophysiological features of both early and late dumping syndrome.

Roux-en-Y gastric bypass in mice--surgical technique and characterisation.

BACKGROUND: A reproducible Roux-en-Y gastric bypass (RYGB) model in mice is needed to study the physiological alterations after surgery. METHODS: Male C57BL6 mice weighing 29.0 ± 0.8 g underwent either RYGB (n = 14) or sham operations (n = 6). RYGB surgery consisted of a small gastric pouch (~2 % of the initial stomach size), a biliopancreatic and alimentary limb of 10 cm each and a common channel of 15 cm. Animals had free access to standard chow in the postoperative period. Body mass and food intake were recorded for 60 days. Bomb calorimetry was used for faecal analysis. Anatomical rearrangement was assessed using planar X-ray fluoroscopy and computed tomography (CT) after oral Gastrografin® injection. RESULTS: RYGB surgery led to a sustained reduction in body weight compared to sham-operated mice (postoperative week 1: sham 27.8 ± 0.7 g vs. RYGB 26.5 ± 1.0 g, p = 0.008; postoperative week 8: sham 30.7 ± 0.8 g vs. RYGB 28.4 ± 1.1 g, p = 0.003). RYGB mice ate less compared to shams (sham 4.6 ± 0.2 g/day vs. RYGB 4.3 ± 0.4 g/day, p < 0.001). There were no differences in faecal mass (p = 0.13) and faecal energy content (p = 0.44) between RYGB and shams. CT scan demonstrated the expected anatomical rearrangement without leakage or stenosis. Fluoroscopy revealed rapid pouch emptying. CONCLUSIONS: RYGB with a small gastric pouch is technically feasible in mice. With this model in place, genetically manipulated mouse models could be used to study the physiological mechanisms involved with metabolic changes after gastric bypass.

Laparoscopic totally stapled entero-enterostomy: a safe and reproducible new technique.

BACKGROUND: Laparoscopic gastric bypass for morbid obesity is a technically demanding procedure, partially because of the necessity to construct two anastomoses. In this study, a new technique to perform the entero-enterostomy is presented. METHODS: We evaluated the procedure in a consecutive series of 100 patients who underwent laparoscopic gastric bypass. Intra- and postoperative complications were analyzed. RESULTS: No complications in relation to the construction of the entero-enterostomy occurred. No leakage, kinking, or stenosis were observed during a mean follow-up of 13.5 months (range 6-20 months). CONCLUSION: This new technique for a totally stapled entero-enterostomy can be recommended.

Laparoscopic totally stapled entero-enterostomy: a safe and reproducible new technique.

BACKGROUND: Laparoscopic gastric bypass for morbid obesity is a technically demanding procedure partially because of the necessity to construct two anastomoses. In this study, a new technique to perform the entero-enterostomy is presented. METHODS: We evaluated the procedure in a consecutive series of 100 patients who underwent laparoscopic gastric bypass. Intra- and postoperative complications were analyzed. RESULTS: No complications in relation to the construction of the entero-enterostomy occurred. No leakage, kinking, or stenosis was observed during a mean follow-up of 13.5 months (range 6-20 months). CONCLUSION: This new technique for a totally stapled entero-enterostomy can be recommended.

Magnetic state around cation vacancies in II-VI semiconductors.

The magnetic properties of neutral cation vacancies in II-VI semiconductors are examined using first principles calculations and group theory. A molecular cluster model of a single vacancy in II-VI semiconductors is developed to explain the observed chemical trend. We show that a single Zn vacancy in ZnO yields a total spin ST=1 in agreement with experiments. But for the other less ionic Zn-based II-VI semiconductors ZnA (A=S, Se, Te) this spin triplet state is nearly degenerate with a nonmagnetic spin singlet state.

Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents.

AIMS/HYPOTHESIS: High levels of inflammation locally in the graft during the initial days after transplantation can cause primary non-function (PNF) of grafted xenogeneic islets in NOD mice. The aim of this study was to explore in a model of spontaneous diabetes, the NOD mouse, the potential of anti-inflammatory agents in the prevention of PNF after xenogeneic islet transplantation. METHODS: Spontaneously diabetic NOD mice were transplanted with 300 rat islets. Animals were treated with acetylsalicylic acid (AsA), rofecoxib, TGF-beta or IL-1 receptor antagonist (IL-1ra). Intra-graft expression of inflammation-related molecules was measured by real time PCR 8 h post-transplantation. At the same time point, plasma nitrite levels were measured. RESULTS: Xenogeneic islets transplanted in control spontaneously diabetic mice resulted in PNF in 16 out of 38 mice (42%). Initial graft loss was not altered by administration of rofecoxib (30%) or TGF-beta (25%). AsA reduced the rate of rapid graft loss to 8% ( p<0.05 vs controls) and administration of IL-1ra even totally prevented PNF (0%, p<0.05 vs controls). Furthermore, all therapies prolonged the mean survival time of xenogeneic islet grafts. The inhibition of PNF by AsA was associated with decreased intra-islet levels of inflammation-related molecules (IL-1, TNF-alpha, iNOS, COX-2) and chemokines (MCP-1 and MIP-3alpha). Finally, also a diminished production of systemic nitrite levels was observed in AsA- and IL-1ra-treated islet recipients. CONCLUSIONS/INTERPRETATION: These data show that treatment with AsA or IL-1ra prevents PNF after islet transplantation in spontaneously diabetic NOD mice. Moreover, the involvement of non-specific inflammation is recognized in xenogeneic islet PNF in spontaneously diabetic NOD mice.

Dimensionality-dependent self-energy corrections and exchange-correlation potential in semiconductor nanostructures.

We study the quasiparticle gap in semiconductor nanostructures versus dimensionality and compare it to the value obtained in the local density approximation. We first develop general arguments based on the GW approach which we then substantiate numerically by a tight binding version of this theory. We show that the gap correction is dominated by a macroscopic surface self-polarization term and point out its nonmonotonic behavior versus dimensionality.

Anatomy and histology of the brain and sense organs of the Antarctic eel cod Muraenolepis microps (Gadiformes; Muraenolepididae).

Brain regions, cranial nerves, and sense organs in Muraenolepis microps, an Antarctic gadiform fish, were examined to determine which features could be attributed to a gadiform ancestry and which to habitation of Antarctic waters. We found that the central nervous system and sense organs are well developed, showing neither substantial regression nor hypertrophy. A detailed drawing of the brain and cranial nerves is provided. The rostral position of the olfactory bulbs and telencephalic size and lobation are common for the order. The optic tectum and corpus cerebelli are smaller than in most other gadiforms. The shape of the corpus cerebelli is not distinctive among gadiforms. The lateral line region is moderately well-developed, but not hypertrophied to the extent seen in deep-sea gadiforms. As is the case in gadids possessing barbels and elongated pelvic rays, Muraenolepis has well-developed facial lobes, although these are smaller and more laterally positioned. The vagal lobes are deeply placed in the rhombencephalon and project into the fourth ventricle. The brain of Muraenolepis resembles that of a phyletically derived gadoid, especially a phycid, more than it resembles the brain of a phyletically basal macrourid. Two histological features of the diencephalon of Muraenolepis appear to be unique among gadiforms: a well-organized thalamic central medial nucleus and subependymal expansions. Muraenolepis has a pure rod retina like many deep-sea species but lacks the superimposed layers of rod outer segments. The histology of the nonvisual sense organs, especially the olfactory and external taste systems, are well-developed in Muraenolepis but not hypertrophied. We relate our findings to what is known about neural morphology in other gadiforms and in phyletically distant notothenioids and liparids that are sympatric with Muraenolepis on the Antarctic shelf. The only feature that reflects an Antarctic existence is the diencephalic subependymal expansions, which within notothenioids mirror the habitation of cold waters and have been found in every Antarctic species examined to date. Although the waters of the Antarctic shelf are cold, dark, and deep, brain and sense organ morphology in Muraenolepis are remarkably free of extreme specialization.

Excitonic and quasiparticle gaps in Si nanocrystals

We present calculations of the one- and two-particle excitations in silicon nanocrystals. The one-particle properties are handled in the GW approximation, and the excitonic gap is obtained from the Bethe-Salpeter equation. We develop a tight binding version of these methods to treat clusters up to 275 atoms. The self-energy and Coulomb corrections almost exactly cancel each other for crystallites with radius larger than 0.6 nm. The result of this cancellation is that one-particle calculations give quite accurate values for the excitonic gap of crystallites in the most studied range of sizes.

Nervous and sensory system correlates of an epibenthic evolutionary radiation in antarctic notothenioid fishes, genus Trematomus (Perciformes; Nototheniidae).

The perciform suborder Notothenioidei consists of 120 species, with 94 confined to the Antarctic Region of the Southern Ocean. On the Antarctic shelf, this phyletic radiation has been accompanied by a substantial morphological and ecological diversification towards a pelagic existence. For example, the primarily benthic genus Trematomus contains an epibenthic radiation that includes T. loennbergii, T. lepidorhinus, and T. eulepidotus. By comparing these epibenthic species with three congeneric benthic species (T. scotti, T. pennellii, and T. bernacchii) we tested three null hypotheses regarding brain variation in Antarctic trematomids: 1) that there is no difference in brain morphology among the six species; 2) that phylogenetic and ecological factors do not influence brain morphology; and 3) that peripheral sensory structures do not influence brain morphology. We rejected each of these hypotheses, leading us to conclude that Trematomus brains vary interspecifically, between benthic and epibenthic species, and with a species' depth distribution. Further, we conclude that brain variation is correlated with differences in peripheral sensory systems and motor activity. Specifically, epibenthic Trematomus have larger percentages of their brain volume devoted to lateral line mechanoreceptive and motor (cerebellar) structures. Species living at greater depths have low ratios of cones:rods in the retina and larger olfactory structures.

Strategies for assessing the implications of malformed frogs for environmental health.

The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level. Discussions highlighted possible causes and recent findings directly related to frog deformities and provided insight into problems and strategies applicable to continuing investigation in several areas. Possible causes of the deformities were evaluated in terms of diagnostics performed on field amphibians, biologic mechanisms that can lead to the types of malformations observed, and parallel laboratory and field studies. Hydrogeochemistry must be more integrated into environmental toxicology because of the pivotal role of the aquatic environment and the importance of fates and transport relative to any potential exposure. There is no indication of whether there may be a human health factor associated with the deformities. However, the possibility that causal agents may be waterborne indicates a need to identify the relevant factors and establish the relationship between environmental and human health in terms of hazard assessment.

Morphology of the brain and sense organs in the snailfish Paraliparis devriesi: neural convergence and sensory compensation on the Antarctic shelf.

The Antarctic snailfish Paraliparis devriesi (Liparidae) is an epibenthic species, inhabiting depths of 500-650 m in McMurdo Sound. Liparids are the most speciose fish family in the Antarctic Region. We examine the gross morphology and histology of the sense organs and brain of P. devriesi and provide a phyletic perspective by comparing this morphology to that of four scorpaeniforms and of sympatric perciform notothenioids. The brain has numerous derived features, including well-developed olfactory lamellae with thick epithelia, large olfactory nerves and bulbs, and large telencephalic lobes. The retina contains only rods and exhibits a high convergence ratio (82:1). Optic nerves are small and nonpleated. The tectum is small. The corpus of the cerebellum is large, whereas the valvula is vestigial. The rhombencephalon and bulbospinal junction are extended and feature expanded vagal and spinal sensory lobes as well as hypertrophied dorsal horns and funiculi in the rostral spinal cord. The lower lobes of the pectoral fins have taste buds and expanded somatosensory innervation. Although the cephalic lateral line and anterior lateral line nerve are well developed, the trunk lateral line and posterior lateral line nerve are reduced. Near-field mechanoreception by trunk neuromasts may have been compromised by the watery, gelatinous subdermal extracellular matrix employed as a buoyancy mechanism. The expanded somatosensory input to the pectoral fin may compensate for the reduction in the trunk lateral line. The brains of P. devriesi and sympatric notothenioids share well-developed olfactory systems, an enlarged preoptic-hypophyseal axis, and subependymal expansions. Although the functional significance is unknown, the latter two features are correlated with habitation of the deep subzero waters of the Antarctic shelf.

A search for primitive Purkinje cells: zebrin II expression in sea lampreys (Petromyzon marinus).

Zebrin II/aldolase C is a 36 kDa polypeptide expressed by Purkinje cells in the cerebellum of elasmobranchs, teleosts, birds, and mammals, and by octavolateralis pyramidal cells in developing teleosts. To better understand the evolution of these two systems we determined if zebrin II is expressed (1) in previously described primitive Purkinje cells, and (2) in octavolateralis pyramidal cells of sea lampreys (Petromyzon marinus). Ammocete and adult stages were reacted with mab anti-zebrin II. In ammocetes the large pyramidal cells of the anterior octavomotor nucleus (AON) were mab anti-zebrin II immunoreactive, but immunoreactivity was not detected in the cerebellar plate. In adults there was no immunoreactivity in any portion of the brain, including the cerebellar plate and the AON. The data indicate that zebrin II immunoreactivity may prove valuable in studying the development of the octavolateralis system across vertebrates. Three explanations are proposed to account for the absence of zebrin II+ Purkinje cells: aldolase C is expressed in Purkinje cells but the zebrin II epitope has not yet evolved; the zebrin II epitope was present in ancestral lampreys but has since been lost; or sea lampreys do not have Purkinje cells. The evolutionary implications of these results are briefly reviewed.