bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System
Authors: Vidal A. , Clément F.
Published: August 2010

The gonadotrophin‐releasing hormone (GnRH) neurosecretory system involves both endocrine neurones and associated brain cells responsible for the control of GnRH release into the pituitary portal blood. Alternation between a pulsatile regime and the pre‐ovulatory surge is the hallmark of GnRH secretion in ovarian cycles of female mammals. In previous studies, we have introduced a mathematical model of the pulse and surge GnRH generator and derived appropriate dynamics‐based constraints on the model parameters, both to reproduce the right sequence of secretion events and to fulfil quantitative specifications on GnRH release. In the present study, we explain how these constraints amount to embedding time‐ and dose‐dependent steroid control within the model. We further examine under which conditions the oestradiol‐driven surge may be withdrawn by pre‐surge progesterone administration and simulate both oestradiol and progesterone challenges in the pulsatile regime.
Distinct geographical and demographic distribution of hepatitis B virus genotypes in the Canadian Arctic as revealed through an extensive molecular epidemiological survey
Authors: Osiowy C. , Larke B. , Giles E.
Published: August 2010

Summary.  Very little is known of hepatitis B virus (HBV) in Canadian Arctic indigenous populations, where HBV was considered endemic prior to the introduction of HBV vaccine. This study expands upon an HBV seroepidemiological survey conducted between 1983 and 1985 throughout the Canadian Arctic, to characterize HBV in this population. Archived hepatitis B surface antigen (HBsAg)‐positive sera (n = 401) were processed for HBV DNA, followed by sequencing and phylogenetic analysis of the HBsAg‐ and HBcAg‐coding regions. Sixty‐nine per cent of samples (277/401) were DNA positive, with most having low viral load (median 3.4 log 10 IU/mL). The predominant HBV genotype observed was genotype B (HBV/B, 75%), followed by HBV/D (24%) and HBV/A (1%). All HBV/B strains clustered within subgenotype B6, a newly recognized HBV genotype among western circumpolar Inuit and Alaska Native people. HBV/D strains included both D3 (88%) and D4 (12%) subgenotypes, while all HBV/A strains were subgenotype A2. An association of HBV genotype B with Inuit living in the eastern Arctic and an association of genotype D with First Nation (Dene) living in the western Arctic was observed. This study establishes the high prevalence of HBV/B6 and HBV/D genotypes in Arctic populations and reveals their marked distribution within the Canadian Arctic based on geographical and demographic attributes.
Parallel habitat specialization within the wolf spider genusHognafrom the Galápagos
Authors: DE BUSSCHERE C. , HENDRICKX F. , VAN BELLEGHEM S. M. , BACKELJAU T. , LENS L. , BAERT L.
Published: August 2010

Within most island archipelagos, such as the Galápagos, similar ecological gradients are found on geographically isolated islands. Species radiations in response to these ecological gradients may follow different scenarios being (i) a single habitat specialization event followed by secondary colonization of each ecotype on the different islands or (ii) repeated and parallel habitat specialization on each island separately. This latter scenario has been considered less likely as gene flow might hamper such ecotypic differentiation. At least for the Galápagos, the extent to which this process is involved in species radiations remains yet poorly understood. Within the wolf spider genusHogna, seven species are described that can be divided into three different ecotypes based on general morphology and habitat preference i.e. species that inhabit the pampa vegetation in the highlands, species that occur in coastal dry habitats and one generalist species. Comparison of the species phylogeny based on one mitochondrial (COI) and one nuclear (28S) gene fragment convincingly demonstrates that ‘pampa’ and ‘coastal dry’ species evolved in parallel on the islands Santa Cruz and San Cristóbal. Despite the observation that allozymes analysis indicated that each species forms a distinct genetic cluster, phylogenetic divergence within these species complexes was very low and paraphyletic and most likely due to hybridization rather than incomplete lineage sorting, as demonstrated for the Santa Cruz species complex. This suggests that within‐island speciation occurred under low levels of gene flow. Species phylogeny in general did not follow the progression of island emergence as a molecular clock analysis suggested that island endemic species may have diverged after as well as before the emergence of the islands. This represents the first clear example of parallel and within‐island speciation because of habitat specialization on the Galápagos and that such divergence most likely occurred under historic gene flow.
Temporal anatomy of an epigenetic switch in cell programming: the white‐opaque transition of C. albicans
Authors: Lohse Matthew B. , Johnson Alexander D.
Published: August 2010

The human pathogen Candida albicans undergoes a well‐defined switch between two distinct cell types, named ‘white’ and ‘opaque’. White and opaque cells differ in metabolic preferences, mating behaviours, cellular morphologies and host interactions. Each cell type is stable through many generations; switching between them is rare, stochastic and occurs without any known changes in the primary sequence of the genome; thus the switch is epigenetic. The white‐opaque switch is regulated by a transcriptional circuit, composed of four regulators arranged in a series of interlocking feedback loops. To understand how switching occurs, we investigated the order of regulatory changes that occur during the switch from the opaque to the white cell type. Surprisingly, changes in key transcriptional regulators occur gradually, extending over several cell divisions with little cell‐to‐cell variation. Additional experiments, including perturbations to regulator concentrations, refine the signature of the commitment point. Transcriptome analysis reveals that opaque cells begin to globally resemble white cells well before they irreversibly commit to switching. We propose that these characteristics of the switching process permit C. albicans to ‘test the waters’ before making an all‐or‐none decision.
Myoelectrical Activity of the Stomach in Gastric Ulcer Patients: An Electrogastrographic Study
Authors: Geldof Han , van der Schee Evert J. , Smout André J. P. M. , van de Merwe Joop P. , van Blankenstein Mark , Grashuis Jan L.
Published: August 2010

This study of gastric ulcer patients examined whether characteristic abnormalities in the fasting and postprandial gastric myoelectrical activity could be discerned electrogastrographically and whether these abnormalities, if present, were related to ulcer characteristics and complaints of nausea and vomiting. A total of 61 recordings were made in 31 gastric ulcer patients, both at the time of diagnosis and after ulcer healing, and these were compared to 52 recordings made in 52 control subjects. Several types of abnormal gastric myoelectrical activity were found in patients with an active ulcer: 1) instability of both the fasting and postprandial gastric frequency; 2) absence of the normal postprandial amplitude increase in the electrogastrogram; 3) waveform changes in the electrogastrographic signal in both the fasting and postprandial states; and 4) tachygastrias. These abnormalities were predominantly found in ulcer patients with symptoms of nausea and vomiting. They disappeared with ulcer healing and resolution of nausea and vomiting. These findings indicate that the abnormalities in gastric myoelectrical activity found in gastric ulcer patients are not merely due to the presence of the ulcer itself, but are associated with the presence of nausea and vomiting.
Motility Effects of Electrical Anterior Sacral Nerve Root Stimulation of the Parasympathetic Supply of the Left Colon and Anorectum in Paraplegic Subjects
Authors: Binnie N. R. , Smith A. N. , Creasey G. H. , Edmond P.
Published: August 2010

The extent and nature of colonic and anorectal motility responses to S2, S3, and S4 anterior nerve root stimulation were studied in seven paraplegic patients with a Brindley electromicturition sacral implant. After sequential S2, S3 and S4 stimulation wave height activity was increased above basal from the transverse colon to the rectum. The mean motility index response to sequential stimulation was greatest at the splenic flexure. The greatest peak wave height and mean motility index response to individual anterior nerve root stimulation was to S3, which could empty the left colon by a distal motility gradient. S4 anterior root stimulation increased the intrarectal pressure and also raised the anal canal pressure to high levels.
Role of Cholecystokinin in Gallbladder and Duodenal Motility in the Interdigestive State of Dogs
Authors: Thor Piotr , Konturek Stanislaw J. , Laskiewicz Janusz , Maczka Malgorzata
Published: August 2010

This study was designed to determine the role of cholecystokinin (CCK) in the motility patterns of duodenum and gallbladder in fasted conscious dogs. During the naturally occurring activity front in the duodenum a significant increase in the motility index, (MI) of the gallbladder was accompanied by a decrease in the gallbladder volume from about 28 ± 4 ml (control) to 21 ± 3 ml. Similar changes in the gallbladder were observed after intravenous bolus injections of motilin (20 to 40 ng/kg), which gave increments in plasma motilin comparable to those occurring spontaneously during the activity front but failed to affect plasma levels of CCK. Blocking of CCK receptors by L‐364, 718 (0.5 to 1 mg/kg) delayed the occurrence of the spontaneous activity front in the duodenum and the accompanying alterations in the gallbladder motility. CCK receptor antagonism abolished the premature activity front induced by motilin in both the duodenum and the gallbladder, converted the fed‐like pattern induced by exogenous CCK to a fasted motility pattern in the duodenum and prevented CCK‐induced reduction in the gallbladder volume. Atropine (12.5 μg/kg) blocked the spontaneous activity front in the duodenum and accompanying alterations in the gallbladder motility and volume but failed to affect those induced by motilin. We conclude that the motility of the gallbladder in fasted dogs shows cyclic changes with typical reduction in the organ volume coinciding with the spontaneous or motilin‐induced activity front in the duodenum, and that both CCK and muscarinic receptors are involved in the MMC‐related alterations in the motor activity of the gallbladder.
Colon Motility in Opiate Addiction and Naloxone‐Precipitated Withdrawal
Authors: Cheskin Lawrence J. , Shabsin Harry S. , Brooner Robert , Schuster Marvin M. , Whitehead William E.
Published: August 2010

More than half of those who use opiates suffer from constipation, and withdrawal from opiates produces abdominal cramps and diarrhea in 70% to 85%. These withdrawal symptoms may influence the number of opioid‐dependent patients who attempt abstinence and the number who relapse. To characterize the motility correlates of these gastrointestinal symptoms of withdrawal, six patients from a drug treatment program were studied while on maintenance doses of methadone (average of 57.5 mg/d) and during acute naloxone‐precipitated withdrawal. Motility was recorded via open‐tipped catheters at 30 cm and 15 cm from the anal verge during a 15‐minute baseline period and for 15 minutes during mechanical distention of the rectosigmoid colon with a balloon. This sequence was repeated during withdrawal. Subjective symptoms and objective signs of withdrawal assessed at 15‐minute intervals showed that all six patients experienced withdrawal. Sigmoid and rectal motility were also assessed in 18 opiate‐free control subjects. Long‐term methadone use was associated with normal sigmoid and rectal motility under baseline conditions, but methadone users did not show the inhibition in sigmoid motility that normal subjects exhibited following baloon distention. When withdrawal was precipitated by naloxone, methadone users showed significant increases in rectosigmoid motility in association with signs and symptoms of withdrawal.
Effect of Esophageal Acid Exposure on Upper Esophageal Sphincter Pressure
Authors: Wilson Janet A. , Pryde Anne , Macintyre Cecilia C. A. , Heading R. C.
Published: August 2010

To investigate the relationship between gastroesophageal reflux and upper esophageal sphincter (UES) pressure, total esophageal acid exposure times on 23‐hour ambulatory pH monitoring were compared with UES manometric results in 98 subjects, 85 with laryngopharyngeal symptoms and 13 asymptomatic controls. There was no correlation of acid exposure time with tonic UES pressure nor with any UES wet swallow parameter. The response of the UES to acute upper esophageal acid infusion was assessed in another 13 patients by a sleeve catheter. There was no significant increase of tonic sleeve UES pressure during acid infusion. In contrast to most previous reports, our results indicate that esophageal acid exposure, whether acute or chronic, has little influence on the UES.
Effect of Intraduodenal Infusion of Acid on the Antropyloroduodenal Motor Unit in Human Volunteers
Authors: Houghton L. A. , Kerrigan D. D. , Read N. W.
Published: August 2010

Intraduodenal acid has been shown to delay gastric emptying. We have investigated the effect of infusing hydrochloric acid into the duodenum on the motor activity of the gastric antrum, pylorus, and duodenum in 18 healthy volunteers. Pressures in the gastric antrum, pylorus, and duodenum and the pH in the antrum and duodenum were recorded in response to alternate duodenal infusions of normal saline and 0.1 M isotonic hydrochloric acid at constant (1 or 2 ml/min) or increasing (1, 2, 3.75, and 5 ml/min) rates. Repetitive infusions of acid (1 or 2 ml/min) were associated with 1) a decrease in antral pressure waves (p < 0.05), 2) a reduction in coordinated pressure waves involving the duodenum (p < 0.05) and replacement by random contractile activity, and 3) an increase in isolated pyloric pressure waves (IPPWs) (p < 0.05). Increasing the rate of acid infusion reduced the rate of coordinated contractions involving the antrum (r = ‐0.39; p < 0.01) and increased the rate of IPPWs (r = 0.45; p < 0.01). There were significant correlations between the percentage of time that the duodenal pH was less than 2, and both the rate of coordinated contractions involving the antrum (r = ‐0.28; p < 0.01) and the rate of IPPWs (r = 0.34; p < 0.01). These changes in antropyloroduodenal motor activity may contribute to the delay in emptying of acidic solutions from the stomach.
Inhibition of Gastric Motor Function by Circulating Corticotropin‐Releasing Factor in Anesthetized Rats
Authors: Raybould H. E. , Koelbel C. B. , Mayer E. A. , Taché Y.
Published: August 2010

We have investigated the influence of intravenous corticotropin‐releasing factor (CRF) on intraluminal pressure of the body of the stomach and the neurohumoral pathways through which CRF inhibits gastric motor function in rats. CRF (0.21–210 pmol) injected intravenously produced a dose‐dependent, long‐lasting decrease in baseline tone and inhibited phasic gastric contractions measured manometrically in urethane‐anesthetized rats. The inhibitory effect of CRF was abolished by administration of hexamethonium or by subdiaphragmatic vagotomy but was unaffected by perineural treatment of the vagus nerves with capsaicin, adrenalectomy, or celiac/superior mesenteric ganglionectomy. Intravenous administration of CRF (126 pmol) inhibited by 69% the emptying of a noncaloric liquid meal as measured by the phenol red technique in conscious rats. Hexamethonium pretreatment significantly attenuated the CRF ‐induced delay in gastric emptying; bretylium, naloxone, adrenalectomy, and celiac I superior mesenteric ganglionectomy had no such effect. In an isolated tissue preparation, CRF (10−11 to 10−6 M) inhibited spontaneous, but not carbachol‐induced, contractions of rat antral longitudinal muscle. The effect of CRF was dose‐dependent and abolished in the presence of tetrodotoxin. These results suggest that peripheral CRF‐induced inhibition of corpus and antral motor contractility may mediate delayed gastric emptying via an action involving a nicotinic synapse, presumably in the enteric nervous system, that requires a vagal input. The in vitro studies support the concept that the action of CRF is not direct on smooth muscle but involves neural transmission within the enteric nervous system.
The Migrating Motor Complex and the Enterohepatic Circulation of Bile Acids: A Scintigraphic Study Using 75Se‐HCAT
Authors: Qvist Niels , Pedersen Svend Arne , Øster‐Jørgensen Erik , Rasmussen Lars , Hovendal Claus Peter , Rasmussen Jens Waever
Published: August 2010

The relationship between the migrating motor complex (MMC) and the enterohepatic circulation was studied in 16 healthy young male volunteers using a combined technique of continuous pressure recording from the gastroduodenal region and scintigraphy with 75Se‐homo‐cholic‐acid‐taurine (75Se‐HCAT). In nine subjects (group 1) the radioactive marker was instilled in the duodenum immediately before a phase III complex of the MMC, and in seven subjects (group 2) in early phase II. In group 1, the gallbladder was visualized by scintigraphy at a median time of 45 (27–90) minutes after instillation of 75Se‐HCAT. Median time for peak radioactivity in distal small intestine and in peripheral blood was 63 (36–144) minutes and 90 (63–135) minutes, respectively. The corresponding figures in group 2 were 108 (81–117), 117 (81–162), and 153 (117–180) minutes. The differences between the median values in the two groups were significant (p < 0.05). The present results demonstrate the importance of phase III in the transport of bile through the small intestine. In addition, they support the contention of jejunal absorption of cholic‐acid‐taurine.
Gastrointestinal Electrical Activity in the Prairie Dog During Fasting, Feeding, and After High‐Cholesterol Diet
Authors: Calabuig R. , Moody F. G.
Published: August 2010

This study describes the electromyographic characteristics of the gastrointestinal tract of prairie dogs, and examines the effects of a 1.2% cholesterol diet on intestinal myoelectrical activity. Twelve prairie dogs were implanted with eight bipolar electrodes in the stomach and small bowel. Recordings were obtained during fasting (n = 12), gastric instillation of food (n = 7), and chronic cholesterol feeding for 3 weeks (n = 7). Gastric slow waves had a frequency per minute of 4.9 ± 1. Intestinal slow waves had a frequency per minute of 19.1 ± 2 in the duodenum, and of 16.8 ± 1 in the ileum. The migrating myoelectric complex (MMC) was identified, with an interval between two consecutive phases I of 145 ± 33 minutes. The delivery of diets of equal weight into the stomach interrupted fasting activity for approximately 3 hours. This was followed by a duodenal phase III and return of the fasted pattern. The interval between the first two postprandial phases I of the MMC not only was shorter than in the fasted state, but also was shorter after cholesterol diet than after regular diet (89 ± 33 min versus 116 ± 24 min, p ≤ 0.05). Chronic feeding of cholesterol diet did not affect the length of the MMC. In conclusion, the gastrointestinal tract of prairie dogs exhibits slow waves, spike bursts, and an MMC that is interrupted by feeding. High‐cholesterol diet does not induce significant changes in the pattern of electrical activity.
Interstitial cells of Cajal: are they major players in control of gastrointestinal motility?
Authors: DANIEL E. E. , BEREZIN I.
Published: August 2010

This review examines recent evidence from structural and functional studies that interstitial cells of Cajal (ICC) play a major role in control of gastrointestinal function. These cells, identified to date only by their structural and somewhat selective staining characteristics, form networks in the region of the myentehc plexus and in or adjacent to circular muscle. Those in circular muscle are often coupled to one another and to smooth muscle cells by gap junctions and are closely innervated by a high proportion of enteric nerves, especially those containing vasoactive intestinal polypeptide (VIP). ICC in the myenteric plexus often have no visible connections by gap junctions to smooth muscle. There is a growing body of evidence from study of small intestine and colon that these cells are either the pacemakers or provide clocks for the pacemaking function of the gut (vahously known as slow waves, pacesetter potentials or control potentials). Additional evidence suggests that they may play a role in neurotransmission of non‐adrenergic, non‐cholinergic inhibitory activity. This review summarizes our current understanding and attempts to point the way for future research.
The effects of acute exercise on colonie motility
Authors: CHESKIN L. J. , CROWELL M. D. , KAMAL N. , ROSEN B. , SCHUSTER M. M. , WHITEHEAD W. E.
Published: August 2010

Abstract Changes in colonic motor activity during aerobic exercise were investigated in ten regularly exercising volunteers (five males and five females) aged 27–70 years. Motility was recorded with a catheter containing three solid‐state pressure transducers spaced 5 cm apart. The motility catheter was advanced 40–50 cm from the anal verge by flexible sigmoidoscope without anesthesia at least 60 min prior to testing. Manometric recordings were made from the colon during a 1‐h pre‐exercise rest period, 1 h of jogging at 70–80% maximum heart rate, and 1‐h post‐exercise rest period. The dominant frequency of contractile activity in the colon shifted from 1–4 cpm during rest, to 4–9 cpm with the onset of exercise. Activity also shifted from sporadic, isolated contractions to regular, propagated contractions in six of ten subjects, five of whom reported a history of runner's diarrhoea. The dominant frequency returned to 1–4 cpm during the post‐exercise period. These changes in distal colonie motility may account for the diarrhoea which some subjects experience during intense, acute exercise.
Characterization of colonic motor activity in conscious dogs
Authors: SHIBATA C. , SASAKI I. , MATSUNO S. , MIZUMOTO A. , IWANAGA Y. , ITOH Z.
Published: August 2010

Diurnal changes in canine colonic motility were investigated by means of chronically implanted force transducers. A characteristic of the colonic motor profile in the fasted state was the occurrence of colonic motor complexes consisting of tonic contractions superimposed with phasic ones. On feeding, motor complexes were immediately induced in the whole colon and continued to occur at significantly shorter intervals than those in the fasted state, but the duration and the amplitude of the colonic motor complexes were not affected by feeding. This increased activity period lasted for 8–16 h after feeding, and 83.3% of the defecations were observed in this period. Of the defecations 33% occurred in the first 2 h after feeding (P < 0.05). More than 80% of the giant migrating contractions associated with defecation propagated from the middle to the distal colon, and the start of faeces evacuation coincided with the end of the relaxation period of the distal colon preceding the arrival of the giant migrating contractions. More than 90% of the giant migrating contractions not associated with defecation migrated from the proximal to the middle colon. More than 60% of the colonic motor complexes migrated in an aboral direction and about 18% of them in an oral direction. These results suggest that (1) defecations tend to occur immediately after feeding; (2) the regional distribution of giant migrating contractions was different between those associated and not associated with defecation.
Anatomical relationship between crural diaphragm and lower oesophageal sphincter: an electrophysiological study
Authors: HEINE K. J. , DENT J. , MITTAL R. K.
Published: August 2010

We performed electrophysiological studies in 12 normal, healthy subjects to determine the relative locations of the lower oesophageal sphincter, crural diaphragm and squamocolumnar junction. Oesophagogastric junction pressure, crural diaphragm electromyogram and mucosal potential difference were measured using a specially designed catheter. This catheter had a side hole to measure pressure and electrodes placed around the side hole for crural diaphragm electromyogram recordings. Mucosal potential difference was measured at the side hole that measured pressure. Recordings were obtained using a motorized rapid pullthrough at a constant speed of 0.85 cm/sec. Rapid pullthroughs were performed under the following conditions: (a) end expiration (diaphragm relaxed), (b) during a sustained maximal contraction of the diaphragm, and (c) during 50% of maximal diaphragmatic contraction. Our results show that the lower oesophageal sphincter is 4.4 cm in length, 2 cm of which is located in the abdomen. The crural diaphragm is 1.7 cm in length and surrounds the proximal half of the lower oesophageal sphincter. The squamocolumnar junction is located in the upper half of the lower oesophageal sphincter in the majority of subjects. The relative location of the lower oesophageal sphincter to the crural diaphragm does not change during diaphragmatic contraction. We conclude that a part of the lower oesophageal sphincter is located in the abdomen. The intra‐abdominal location of the lower oesophageal sphincter may be important for its anti‐reflux barrier function.
Post‐prandial and interdigestive return of bile acids to the gallbladder in healthy subjects
Authors: QVIST N. , ØSTER‐JØRGENSEN E. , PEDERSEN S. A. , RASMUSSEN L. , HOVENDAL C.
Published: August 2010

The enterohepatic circulation of a radioactive marked bile acid (75Se‐HCAT) was studied by scintigraphy in the post‐prandial period as well as after prolonged fasting in healthy young male volunteers in combination with a continuous pressure recording from the antroduodenal region. In a group of 8 subjects the radioactive marker was instilled into duodenum after the ingestion of a standard meal. At the transition from fed‐motility pattern (irregular contractions with a frequency of 1–9 per minute) to fasting intestinal motility pattern, defined as the occurrence of a Phase HI activity‐front of the migrating motor complexes, a median (range) of 14% (9–25%) of the 75Se‐HCAT pool was stored in the gallbladder. During the following migrating motor complex cycles, net gallbladder filling occurred with a significantly higher rate during Phase I (0.22% of the 75Se‐HCAT pool per minute) compared to Phase II, where the median net value was 0.07%. This difference in net filling rate was due to the occurrence of periods of gallbladder emptyings during Phase II. At the end of this first migrating motor complex cycle in the post‐prandial period a total of 32% (26–46%) of the 75Se‐HCAT pool was in the gallbladder. In another group of 8 subjects the scintigraphic study was not carried out until 15–20 hours after ingestion of the standard meal and the radioactive marker. The scintigraphic study was carried out for two subsequent migrating motor complex cycles, and the amount of the 75Se‐HCAT pool present in the gallbladder at the first recorded Phase III complex was 46% (32–52%). The figures at the occurrence of the following two Phase III complexes were 48% (32–65%) and 47% (42–59%), respectively. A cyclic variation in gallbladder filling and emptying in connection with the migrating motor complex cycle was seen with a net filling during Phase I and a net emptying during Phase II. In the study after prolonged fasting the number and duration of the spontaneous gallbladder emptyings in Phase II were not different from those in the post‐prandial study. However, the amount emptied in per cent of the 75Se‐HCAT pool was significantly higher in the group studied after prolonged fasting compared to the group studied in the postprandial period, and accounted for a median of 3.3% (2.0–16.5%) and (1.6–6.0%) of the 75Se‐HCAT pool, respectively. This difference is most likely due to an increase in the concentration of gallbladder bile during fasting.
Effect of motilin and erythromycin on the motor activity of the human colon
Authors: BRADETTE M. , POITRAS P. , BOIVIN M.
Published: August 2010

Motilin and motilin receptor agonist erythromycin were administered to healthy subjects where colonic motility was recorded manometrically from the hepatic flexure to the rectum. Experiments were carried out during the fasting basal state or when colonic motility was stimulated by the ingestion of a 1000 kcal lunch. A supraphysiological dose of motilin (100 ng kg−1, i.v.) increased the motor activity of the fasting sigmoid colon, but the response was smaller than the meal induced activity. The administration of erythromycin (200 mg, i.v.) during the inter digestive period induced, on the sigmoid region, a motor response that was not significantly different in amplitude from the post‐prandial contractile profile. However, on the more proximal segments of the colon, motilin and erythromycin were inactive. When both agents were administered during the digestive period, both failed to modify the contractile stimulation normally seen in all regions of the colon after a meal. Therefore the colonic motor response obtained with stimulation of motilin receptors in man appears limited;it is restricted to the sigmoid, it can be seen only during fasting and it is of weak amplitude.
Effect of fat preload on gastric myoelectrical activity in normal humans
Authors: CHEN J. D. Z. , DAVENPORT K. , McCALLUM R. W.
Published: August 2010

The aim of this study was to investigate the effect of fat preload on gastric myoelectrical activity in normal humans. The study was performed in 10 normal subjects (five males, five females) fasted for 6h or more. Gastric myoelectrical activity was recorded using surface abdominal electrodes. In the study session the subjects ingested a 40‐g liquid fat meal (2 oz of lipomul) after a 30‐min baseline recording. A test meal (225 kcal beef stew) was then consumed 15 min after drinking the lipomul, and the recording was continued for 2 h after the test meal. The control session performed on a separate day followed the same procedure except that the lipomul was replaced by 2 oz of water. The order of the study and control sessions was randomized. The cutaneous recording of gastric myoelectrical activity (electrogastrogram or EGG) was digitized and subjected to computerized quantitative data analysis. The peak power and the corresponding frequency of the EGG during every 15‐min time interval were computed using spectral analysis. Student's t‐test was applied to determine the effect of fat preload on the surface recording of gastric myoelectrical activity. It was found that: (1) the power of the 15‐min EGG at the dominant frequency immediately after fat preload was significantly lower than that of the baseline EGG (P = 0.01); (2) the postprandial power increase of the EGG at the dominant frequency was significantly lower with fat preload than with placebo preload (P = 0.002); (3) the dominant frequency of the EGG was not affected by fat preload. It was concluded that fat preload significantly decreases the power of the EGG but does not affect the frequency of the gastric slow wave.
Effect of various doses of erythromycin on colonic myoelectrical activity in IBS patients
Authors: DELVAUX M. , LOUVEL D. , FIORAMONTI J. , STAUMONT G. , BUENO L. , FREXINOS J.
Published: August 2010

Abstract Erythromycin mimics the effects of motilin but its action on colonic motility is still controversial. The aim of this study was to evaluate the effect of intravenous infusions of various doses of erythromycin on colonic motility in patients with irritable bowel syndrome (IBS).

At 09.00 hours, day 1 (D1), an intraluminal probe was introduced up to the right colon in 24 IBS patients with myoelectrical activity recorded for 48 h. Patients were randomised in three groups of eight, receiving either erythromycin 1.5, 3 or 7 mg kg−1. All were investigated as follows: at 09.00 hours, D2, fasted patients were infused with erythromycin in 30 min; at 09.00 hours, D3, glycerol 10 ml was injected intraluminally. Colonic activity was measured 30 min before the infusion started, during and 30 min after it, separately in the left and right colons, and expressed in time occupied during the recording period.

Basal activity was similar in both parts of the colon. During and after erythromycin 1.5 and 3 mg kg−1, colonic activity remained unchanged. Erythromycin 7 mg kg−1 induced a moderate increase in spiking activity (long spike bursts or LSBs + 33%; migrating LSBs or MLSBs + 41%) in the right colon, no change being statistically significant; activities in the left colon were similar to basal level.

During the first 30 min following glycerol injection, mean short spike burst or SSB activity did not change, mean LSB activity increased by seven fold (P = 0.014) and MLSB activity by ten fold (P = 0.023).

Erythromycin at doses from 1.5 to 7 mg kg−1 failed to stimulate colonic motility in IBS patients. By contrast, response to glycerol was strong, suggesting normal colonic responsiveness. Erythromycin stimulatory effects could be limited to the upper gut at least in IBS patients.
Earliest Triassic microbialites in Çürük Dag, southern Turkey: composition, sequences and controls on formation
Authors: KERSHAW STEVE , CRASQUIN SYLVIE , FOREL MARIE‐BÉATRICE , RANDON CARINE , COLLIN PIERRE‐YVES , KOSUN ERDAL , RICHOZ SYLVAIN , BAUD AYMON
Published: August 2010

The Permian–Triassic Boundary sequence at Çürük Dag, near Antalya, Turkey, begins with a major erosion surface interpreted as being the Late Permian lowstand, on which lies ca 0·4 m of grainstone/packstone composed of ooids, peloids and bioclasts. Most ooids are superficial coats on fragments of calcite crystals presumed to be eroded from crystal fans which are no longer present. The erosion surface is smooth and shows no evidence of dissolution; the grainstone/packstone contains intraclasts of the underlying wackestone, proving erosion. Next are 15 m of microbialite comprised of interbedded stromatolites, thrombolites, plus beds of planar limestones with small‐scale erosion. The latter comprise a complex interlayering of stromatolitic, thrombolitic and peloidal fabrics and precipitated crystal fans, which form a hybrid of microbialite and inorganic carbonate, together with bioclastic debris and micrite. The Çürük Dag microbialite sequence is repetitious; the lower part is more complex, with abundant stromatolites and hybrid microbialites. Some of the stromatolites are themselves hybrids composed of peloids and crystal fans. In the upper part of the sequence stromatolites are missing and the rock is composed mostly of recrystallized thrombolites that develop upwards from tabular to domal form. The domes form directly below small breaks in microbialite growth where very thin shelly micrites and grainstones/packstones are deposited. Repetition of facies may be controlled by sea‐level change; a deepening‐up model is consistent with the evidence. Stromatolites (with abundant crystal fans) dominate in shallower water, deepening through hybrid microbialite and interlayered sediments to thrombolite, probably no more than a few tens of metres deep, followed by breaks and renewal of microbialite growth. An interpretation of open marine fully oxygenated waters for microbialite growth is consistent with ongoing parallel work that has identified Bairdioid ostracods in the microbialite, a group known to be open marine. However, other researchers have proposed low oxygen conditions for Permian–Triassic boundary facies globally, so work continues to confirm whether the Çürük Dag microbialite grew in dysoxic or normally oxygenated conditions. The principal stimulus for post‐extinction microbialites is likely to be carbonate supersaturation of the oceans. The microbialite sequence is overlain by a further 25 m of grainstone/packstone (without microbialite), followed by Early Triassic shales. Overall, microbialites form a thin aggradational sequence during an overall relative sea‐level rise, consistent with global eustatic rise following the Late Permian lowstand.
Multiple progressive piloleiomyomas in a ferret (Mustela putorius furo): a case report
Authors: Mialot Martine , Prata Daniela , Girard‐Luc Anne , Rakotovao Farasoa , Cuveillier Jean‐François , Bernex Florence
Published: August 2010

A 2.5‐year‐old ovariectomized female ferret developed multiple progressive linear and raised nodules on the skin. The first lesions occurred on the tail, which was then amputated. Over the following 3 years, additional lesions appeared in the vicinity of the scar and then further rostrally on the flanks and thorax. Histological and immunohistochemical investigation led to a diagnosis of multiple piloleiomyomas. The unique characteristics of this ferret disease are described and compared with those of multiple piloleiomyomas in humans and with those of other cutaneous smooth muscle cell tumours reported in the veterinary literature.
Ineligibility for renal transplantation: prevalence, causes and survival in a consecutive cohort of 445 patients
Authors: Kianda Mireille N. , Wissing Karl M. , Broeders Nulifer E. , Lemy Anne , Ghisdal Lidia , Hoang Anh D. , Mikhalski Dimitri , Donckier Vincent , Vereerstraeten Pierre , Abramowicz Daniel
Published: August 2010

Kianda MN, Wissing KM, Broeders NE, Lemy A, Ghisdal L, Hoang AD, Mikhalski D, Donckier V, Vereerstraeten P, Abramowicz D. Ineligibility for renal transplantation: prevalence, causes and survival in a consecutive cohort of 445 patients. Clin Transplant 2011: 25: 576–583. © 2010 John Wiley & Sons A/S.

Abstract:  Little is known about the proportion of renal transplant candidates who are considered ineligible by the transplant center, the reasons of their ineligibility and their survival during dialysis. In this retrospective, single‐center study of 445 adult patients referred between 2001 and 2006, 36 (8%) were deemed ineligible for medical contraindications. The leading reason was cardiovascular (CV) (75%), specifically aorto‐iliac, and/or limb vessels atheromatosis or calcifications; ischemic heart disease; or a combination thereof. Nine patients had other contraindications that were absolute for three of them; six patients displayed a combination of relative contraindications. When compared to eligible patients (N = 409), those ineligible were significantly older (60 yr vs. 48), more often diabetics (50% vs. 15%), obese (39% vs. 17%) suffering from coronary artery disease (53% vs. 11%) and peripheral arterial disease (86% vs. 11%). Their primary nephropathy was more often diabetic and/or hypertensive/nephroangiosclerosis (61% vs. 23%), and their median dialysis vintage prior to evaluation was longer (29 months vs. 10, p < 0.0001). The actuarial survival of ineligible patients was significantly lower than that of eligible patients (at five yr: 53% vs. 88%). Adequate control of CV risk factors before dialysis and early referral for transplantation might help to improve eligibility of renal transplant candidates.
Long‐term follow‐up of immunosuppressive monotherapy in liver transplantation: tacrolimus and microemulsified cyclosporin
Authors: Cholongitas Evangelos , Shusang Vibhakorn , Germani Giacomo , Tsochatzis Emmanuel , Raimondo Maria Luisa , Marelli Laura , Senzolo Marco , Davidson Brian R. , Patch David , Rolles Keith , Burroughs Andrew K.
Published: August 2010

Cholongitas E, Shusang V, Germani G, Tsochatzis E, Raimondo ML, Marelli L, Senzolo M, Davidson BR, Patch D, Rolles K, Burroughs AK. Long‐term follow‐up of immunosuppressive monotherapy in liver transplantation: tacrolimus and microemulsified cyclosporin. Clin Transplant 2011: 25: 614–624. © 2010 John Wiley & Sons A/S.

Abstract:  Background:  Early withdrawal of steroids after liver transplantation has benefits, but rarely is total avoidance of steroids used. We evaluated long‐term results of patients with ab initio monotherapy with cyclosporin (CYA) vs. tacrolimus (TAC), in randomized and cohort studies.

Methods:  We evaluated long‐term outcomes in 66 adults randomized to TAC or CYA and 94 subsequent patients who received TAC. Protocol liver biopsies were performed. Rejection was treated with three 1 g/d methylprednisolone. Further rejection after two courses of methylprednisolone was defined as monotherapy failure.

Results:  Actuarial five‐yr survival was 68% in TAC and 70% CYA. Monotherapy failed in 8% TAC and 13% CYA patients; no rejection in 24% TAC and 19% CYA patients; 42% TAC and 33% CYA patients were not exposed to any steroids. Rejection episodes were less with TAC, compared to CYA: mean 1.8 vs. 2.5, p = 0.042. Chronic rejection occurred in only 4 (11%) CYA patients. During follow‐up of median 97 months (range: 0.06–145), there were 16 (44%) deaths in CYA and 48 (39%) in TAC patients (p > 0.05).

Conclusions:  TAC monotherapy ab initio is a viable immunosuppressive strategy in liver transplantation and was associated with lower rejection rates and renal complications, compared to CYA.
Difficulty in sustaining hepatic outflow in left lobe but not right lobe living donor liver transplantation
Authors: Shirouzu Yasumasa , Ohya Yuki , Hayashida Shintarou , Asonuma Katsuhiro , Inomata Yukihiro
Published: August 2010

Shirouzu Y, Ohya Y, Hayashida S, Asonuma K, Inomata Y. Difficulty in sustaining hepatic outflow in left lobe but not right lobe living donor liver transplantation. Clin Transplant 2011: 25: 625–632. © 2010 John Wiley & Sons A/S.

Abstract:  Background:  Hepatic outflow block is one of the major complications leading to severe graft dysfunction after left lobe living donor liver transplantation (LDLT).

Methods:  Medical records of 46 recipients of a left lobe LDLT were reviewed. The method of outflow reconstruction and post‐transplant morphological changes of hepatic veins were investigated. The subjects were followed up until September 2008, with a median follow‐up period of 2.0 yr (range: 0.5–5.9 yr).

Results:  There were no multiple outflow tracts to be reconstructed, and the median caliber of the single orifices with or without venoplasty was 32.0 mm. The difference between the angle of hepatic veins to the sagittal plane measured on computed tomography was calculated for pre‐operative donors and post‐operative recipients a month after LDLT. Both left and middle hepatic veins showed a significantly greater change in angle than the right hepatic vein. Both left and middle hepatic veins more frequently showed a nearly flat wave form on Doppler study one month after LDLT. In the 46 recipients of left lobe grafts, three developed outflow block (6.5%).

Conclusions:  The middle and left hepatic veins tend to distort and stretch during graft regeneration. These characteristics seem to be associated with outflow disturbances.
Structure‐activity relationships for some elastin‐derived peptide chemoattractants
Authors: MORELLI M.A. CASTIGLIONE , BISACCIA F. , SPISANI S. , BIASI M. DE , TRANIELLO S. , TAMBURRO A. M.
Published: August 2010

In an attempt to explore the relationships between conformation of chemotactic peptides related to elastin and their biological activity we have studied five peptides: VGVAPG, VGVPG, VGAPG, GVAPG and GGVPG in solvents of different polarities which may mimic the environmental conditions at the receptor site. CD and NMR studies showed that GVAPG has no preference for structured conformations, while the other peptides may assume folded conformations in organic solvents. All these peptides but GGVPG showed chemotactic activity for monocytes. The chemotactic activity of VGVPG, VGAPG and VGVAPG was inhibited by lactose, while chemotaxis of peptide GVAPG was insensitive to lactose, suggesting the existence of different chemotactic receptors.
Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG‐6)
Authors: Licht Rasmus W , Nielsen Jannie N , Gram Lars F , Vestergaard Per , Bendz Hans
Published: August 2010

Licht RW, Nielsen JN, Gram LF, Vestergaard P, Bendz H. Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG‐6). Bipolar Disord 2010: 12: 483–493. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  In industry‐generated pivotal studies, lamotrigine has been found to be superior to placebo and comparable to lithium in the maintenance treatment of bipolar I disorder. Here, we directly compared lamotrigine to lithium under conditions similar to clinical routine conditions.

Methods:  Adult bipolar I disorder patients with at least two episodes within the last five years and an index episode requiring treatment were randomized to lithium (n = 78; doses adjusted to obtain serum levels of 0.5–1.0 mmol/L) or to lamotrigine (n = 77; up‐titrated to 400 mg/day) as maintenance treatments. Randomization took place when clinically appropriate, and comedication was allowed within the first six months after randomization. The patients were enrolled from March 2001 to December 2005, and observations were censored December 2006, allowing a subgroup of patients to be followed for more than five years. The primary outcome measure was time to predefined endpoints indicating insufficient maintenance treatment, and the major secondary outcome measure was time to any study endpoint. Data were analyzed primarily by Cox proportional regression models.

Results:  For the primary outcome measure, the crude Hazard Rate Ratio (HRR) (lamotrigine relative to lithium) was 0.92 [95% confidence interval (CI): 0.60–1.40]. When the primary endpoints were broken down by polarity, the HRRs (lamotrigine relative to lithium) for mania and depression were, respectively, 1.91 (95% CI: 0.73–5.04) and 0.69 (95% CI: 0.41–1.22). There was no between‐group difference in terms of staying in study [HRR: 0.85 (95% CI: 0.61–1.19)]. Most treatment failures occurred within the first 1.5 years of treatment, and, among patients followed for at least five years, practically no patients were maintained successfully on monotherapy with either of the drugs. The lithium‐treated patients reported diarrhea, tremor, polyuria, and thirst more frequently. Two cases, probably lamotrigine‐related, of benign rash occurred.

Conclusions:  No differences in maintenance effectiveness between lithium and lamotrigine could be demonstrated. Lamotrigine was better tolerated than lithium, but apparently this did not influence the outcome.