Descending Research Articles

Establishing a mucosal gut microbial community in vitro using an artificial simulator.

The Twin Simulator of the Human Intestinal Microbial Ecosystem (TWINSHIME®) was initially developed to study the luminal gut microbiota of the ascending (AC), transverse (TC), and descending (DC) colon regions. Given the unique composition and potential importance of the mucosal microbiota for human health, the TWINSHIME was recently adapted to simulate the mucosal microbiota as well as the luminal community. It has been previously demonstrated that the luminal community in the TWINSHIME reaches a steady state within two weeks post inoculation, and is able to differentiate into region specific communities. However, less is known regarding the mucosal community structure and dynamics. During the current study, the luminal and mucosal communities in each region of the TWINSHIME were evaluated over the course of six weeks. Based on 16S rRNA gene sequencing and short chain fatty acid analysis, it was determined that both the luminal and mucosal communities reached stability 10–20 days after inoculation, and remained stable until the end of the experiment. Bioinformatics analysis revealed the formation of unique community structures between the mucosal and luminal phases in all three colon regions, yet these communities were similar to the inoculum. Specific colonizers of the mucus mainly belonged to the Firmicutes phylum and included Lachnospiraceae (AC/TC/DC), Ruminococcaceae and Eubacteriaceae (AC), Lactobacillaceae (AC/TC), Clostridiaceae and Erysipelotrichaceae (TC/DC). In contrast, Bacteroidaceae were enriched in the gut lumen of all three colon regions. The unique profile of short chain fatty acid (SCFA) production further demonstrated system stability, but also proved to be an area of marked differences between the in vitro system and in vivo reports. Results of this study demonstrate that it is possible to replicate the community structure and composition of the gut microbiota in vitro. Through implementation of this system, the human gut microbiota can be studied in a dynamic and continuous fashion.

Microbial Biotransformation of a Polyphenol-Rich Potato Extract Affects Antioxidant Capacity in a Simulated Gastrointestinal Model

A multistage human gastrointestinal model was used to digest a polyphenol-rich potato extract containing chlorogenic acid, caffeic acid, ferulic acid, and rutin as the primary polyphenols, to assess for their microbial biotransformation and to measure changes in antioxidant capacity in up to 24 h of digestion. The biotransformation of polyphenols was assessed by liquid chromatography–mass spectrometry. Antioxidant capacity was measured by the ferric reducing antioxidant power (FRAP) assay. Among the colonic reactors, parent (poly)phenols were detected in the ascending (AC), but not the transverse (TC) or descending (DC) colons. The most abundant microbial phenolic metabolites in all colonic reactors included derivatives of propionic acid, acetic acid, and benzoic acid. As compared to the baseline, an earlier increase in antioxidant capacity (T = 8 h) was seen in the stomach and small intestine vessels as compared to the AC (T = 16 h) and TC and DC (T = 24 h). The increase in antioxidant capacity observed in the DC and TC can be linked to the accumulation of microbial smaller-molecular-weight phenolic catabolites, as the parent polyphenolics had completely degraded in those vessels. The colonic microbial digestion of potato-based polyphenols could lead to improved colonic health, as this generates phenolic metabolites with significant antioxidant potential.

New ultrasonographic evaluation of stool and/or gas distribution for treatment of chronic constipation.

The first aim of this study was to develop a new ultrasonographic method (US) to evaluate stool and/or gas distribution. The second aim was to apply this method to compare stool and/or gas distribution between healthy subjects and patients with chronic constipation and evaluate whether US parameters could be an alternative to the colonic transit time (CTT). We enrolled seven healthy volunteers (four men, three women; mean age 29.3 ± 5.2years) who underwent US and computed tomography (CT) on the same day to evaluate the reproducibility of US results. We then enrolled 268 patients with chronic constipation (94 men, 174 women; mean age 63.3 ± 4.2years) and 66 age- and sex-matched healthy subjects (controls). The transverse diameters of four segments of the colon [ascending (AC), transverse (TC), descending (DC), and sigmoid (SC)] and the rectum (R) were measured, and their stool and/or gas distribution was evaluated using the constipation index (CI) [AC + TC + DC + SC + R/5] and left/right (L/R) distribution [(DC + SC)/(AC + TC)]. The CTT was assessed using radiopaque markers. All healthy subjects underwent US and CT successfully, with a sufficiently high reproducibility coefficient for this method and significant correlation between the US and CT parameters. The stool and/or gas distribution evaluated by US showed a significant difference in one of the US parameters between healthy subjects and patients, and the CI was an indirect indicator for the CTT. These findings may assist physicians evaluate stool and/or gas distribution of patients with chronic constipation, which is an indirect indicator for CTT.

Topographic anatomy of ascending and descending neurons of the supraesophageal, meso- and metathoracic ganglia in paleo- and neopterous insects

Topographic anatomy of ascending (AN) and descending (DN) neurons of the supraesophageal and thoracic ganglia in the nervous system of winged insects (Pterygota) - representatives of infraclasses Plaeoptera (Odonata, Aeschna grandis, dragonfly) and Neoptera (Blattoptera, Periplaneta americana, cockroach) was studied. These insects are different in ecological niches, lifestyles, sets of behavioral complexes, levels of locomotor system development, evolutionary age and systematic position. Neuronal bodies and processes of ANs and DNs were stained with nickel chloride (NiC2), their topography was studied on total prerapations of the supraesophageal and thoracic ganglia. Unlike cockroaches, in dragon- fly protocerebrum DNs sending their processes to ocelli were found. Dragonfly DN processes show a spe- cific type of arborization in thoracic ganglia, with collaterals directed both ipsi- and contralaterally. In cockroaches collaterals of DN processes are arranged ipsilaterally. AN bodies in meso- and metathoracic ganglia of dragonfly lie both ipsi- and contralaterally in respect to the ascending process whereas in cock- roaches AN bodies in the same ganglia are predominantly localized contralaterally. Substantial differences in allocation of DNs and ANs in insects dissimilar in locomotor manner reflect a different extent of supraesophageal ganglion control over activity of segmental centers. It seems related to neither the evolu- tionary age of insects, nor the antiquity of origin, nor their systematic position. Probably, a different de- gree of locomotion control depends on the way of getting food - catching prey in air by <<paleopterous>> dragonflies unlike <<simple>> maneuverable walking or running across a solid substrate by <<neopterous>> cockroaches.

514P - Does Exact Primary Site Impact on Outcome for Metastatic Colorectal Cancer (Mcrc)?

ABSTRACT Aim: Previous reports have described differences in biology and outcome based on whether the primary bowel cancer is right (R) or left (L) sided. Some authors have, however, argued that separating into right and left is too limited and that different patterns still exist within each sub group. Here we aimed to look at each individual primary site and outcomes from the SA mCRC registry to test this hypothesis. Methods: We assessed for differences in patient characteristics and outcomes based on the standard divisions of primary sites; caecum, ascending (AC), hepatic flexure (HF), transverse (TC), splenic flexure (SF), descending (DC), sigmoid (SC), rectosigmoid (RS) or rectal. Kaplan Meier was used for survival outcomes and a descriptive analysis was undertaken for prognostic markers. Results: 2877 patients were analysed. Primary site frequency was as follows; Caecum 14.6%, AC 9.2%, HF 3.1%, TC 6.2%, SF 2.8%, DC 3.9%, SC 21.9%, RS 6.8% and 26.7% rectum (4% unknown). Differences between sites were age, female sex, rates of poorly differentiated pathology, and rate of lung metastasis. There were no subgroups within the R & L division that stood out as behaving differently. Median age was 76.3 yrs for caecum compared with 69.3 yrs for rectum. Female sex was highest in caecum 52.5% vs. 34.9% rectum. Poorly diff pathology, caecum to SF 30-40.7% vs. DC to rectum 18.3-20.9%. Lung metastasis, caecum to SF 3-6% vs. DC to rectum 9.6-12.8%. There was variation in KRAS mutation; highest 59% in caecum, 48% for DC and Conclusions: Cancer of the caecum had the highest proportion of females, poorly differentiated pathology and KRAS exon 2 mutation. Lung metastases were observed more commonly in cancers that originate from the distal colon to rectum as compared to more proximal cancers. R sided primary sites have a poorer outcome consistently than those designated L. Overall, the SA mCRC data supports a distinction between metastatic tumors of right versus left sides origin, with the transition point being at the splenic flexure. Disclosure: All authors have declared no conflicts of interest.

Lactobacillus plantarum IFPL935 impacts colonic metabolism in a simulator of the human gut microbiota during feeding with red wine polyphenols.

The colonic microbiota plays an important role in the bioavailibility of dietary polyphenols. This work has evaluated the impact on the gut microbiota of long-term feeding with both a red wine polyphenolic extract and the flavan-3-ol metabolizer strain Lactobacillus plantarum IFPL935. The study was conducted in the dynamic Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The feeding of the gut microbiota model with red wine polyphenols caused an initial decrease in the counts of total bacteria in the ascending colon (AC), with Bacteroides, Clostridium coccoides/Eubacterium rectale and Bifidobacterium being the most affected bacterial groups. The bacterial counts recovered to initial numbers faster than the overall microbial fermentation and proteolysis, which seemed to be longer affected by polyphenols. Addition of L. plantarum IFPL935 helped to promptly recover total counts, Lactobacillus and Enterobacteriaceae and led to an increase in lactic acid formation in the AC vessel at the start of the polyphenol treatment as well as butyric acid in the transverse (TC) and descending (DC) vessels after 5 days. Moreover, L. plantarum IFPL935 favoured the conversion in the DC vessel of monomeric flavan-3-ols and their intermediate metabolites into phenylpropionic acids and in particular 3-(3'-hydroxyphenyl)propionic acid. The results open the possibilities of using L. plantarum IFPL935 as a food ingredient for helping individuals showing a low polyphenol-fermenting metabotype to increase their colonic microbial capacities of metabolizing dietary polyphenols.

Using live vegetation volume to analyze the effects of plot Pinus massoniana Lamb on water and soil conservation under natural rainfall events

The 3-D spatial distributions of vegetation are of great significance for water and soil conservation but are rarely concerned in literatures. The live vegetation volume (LVV) was used to relate to water/soil loss under 144 natural erosive rainfall events from 2007 to 2010 in a typical water-eroded area of southern China. Quadratic polynomial regression models were established for five pure tree (Pinus massoniana Lamb) plots between LVV and water (runoff)/soil conservation effects (RE/SE). RE/SE corresponds to the ratios of runoff depth/soil loss of the pure tree plots to that of the control plot under each rainfall event. Increasing LVV exhibits descending (DS), descending-ascending (DA), ascending-descending (AD), and ascending (AS) trends in the LVV–RE and LVV–SE curves. The effects of soil conservation on the plots were generally more noticeable than the effects of water conservation, and most of the RE and SE values reflected the positive effects of water and soil conservation. The effects were mainly positive under heavy rains (e.g., rainfall erosivity, R = 140 MJ mm ha−1 h, maximum 30 min intensity, I30 = 16 mm h−1), whereas the effects were mainly negative under light rains (e.g., R = 45 MJ mm ha−1 h, I30 = 8 mm h−1). The trees' water/soil conservation effects notably transformed when rainfall erosivity and intensity were lower than the positive or negative effects to a certain threshold. About 50% rainfall events led to obvious transform effects when LVVs were near 0.5 or 0.6. These results are able to aid in the decision making on the forest reconstruction in water-eroded areas.

Fasting and postprandial volumes of the undisturbed colon: normal values and changes in diarrhea‐predominant irritable bowel syndrome measured using serial MRI

BackgroundPrevious assessments of colon morphology have relied on tests which were either invasive or used ionizing radiation. We aimed to measure regional volumes of the undisturbed colon in healthy volunteers (HV) and patients with diarrhea-predominant irritable bowel syndrome (IBS-D).Methods3D regional (ascending, transverse, and descending) colon volumes were measured in fasting abdominal magnetic resonance (MR) images of 75 HVs and 25 IBS-D patients. Thirty-five of the HV and all 25 IBS-D subjects were fed a standard meal and postprandial MRI data obtained over 225 min.Key ResultsColonic regions were identified and 3D maps from cecum to sigmoid flexure were defined. Fasted regional volumes showed wide variation in both HVs being (mean ± SD) ascending colon (AC) 203 ± 75 mL, transverse (TC) 198 ± 79 mL, and descending (DC) 160 ± 86 mL with no difference from IBS-D subjects (AC 205 ± 69 mL, TC 232 ± 100 mL, and DC 151 ± 71 mL, respectively). The AC volume expanded by 10% after feeding (p = 0.007) in the 35 HV possibly due to increased ileo-colonic inflow. A later rise in AC volume occurred from t = 90 to t = 240 min as the meal residue entered the cecum. In contrast, IBS-D subjects showed a much reduced postprandial response of the AC (p < 0.0001) and a greater increase in TC volume after 90 min (p = 0.0244) compared to HV.Conclusions & InferencesWe have defined a normal range of the regional volumes of the undisturbed colon in fasted and fed states. The AC in IBS-D appeared less able to accommodate postprandial inflow which may account for faster colonic transit.

Estimating the effect of Pinus massoniana Lamb plots on soil and water conservation during rainfall events using vegetation fractional coverage

Abstract Determining the effects of the critical structure of forests on soil and water conservation aids in understanding forest functions and scientific decision-making in management practices. Quadratic polynomial regression models were established for five pure tree ( Pinus massoniana Lamb) plots between vegetation fractional coverage (VFC) and soil/water conservation effects (SCE/WCE) for 144 erosive rainfall events from 2007 to 2010 in Hetian Town, Changting County, Fujian Province, a typical water-eroded area in southern China. The SCE/WCE corresponds to the ratios of soil loss/runoff depth of each tree plot to those of the control plot under each rainfall event. The results show that increasing VFC exhibits descending (DS), descending–ascending (DA), ascending–descending (AD), and ascending (AS) trends in the VFC–SCE and VFC–WCE curves, which indicate positive or negative effects of plot trees on soil and water conservation. In general, the effects on soil conservation on the plots were more notable than those on water conservation, and most of the SCE and WCE values reflect the positive effect of trees on soil and water conservation. Most determination coefficients of both the VFC–SCE and VFC–WCE models exceeded 0.6, and varied with the year and the effect. The positive effects of the pure trees occurred mainly during rainfall events with relatively higher rainfall depth, stronger intensity, and shorter duration, whereas the negative effects occurred mainly during rainfall events with lower rainfall depth, weaker intensity, and longer duration. The transition effects DA and AD appeared largely during rainfall events with moderate rainfall depth, intensity, and duration. The critical VFCs for soil and water conservation during rainfall events were 0.4 and 0.5, respectively, which provided a reference for the evaluation and planning of forest reconstruction in this and similar water-eroded areas.

Abstract P388: Association of Clinical Characteristics and Cardiopulmonary Risk Factors with Aortic and Pulmonary Arterial Enlargement by Magnetic Resonance

Purpose: To determine the association of clinical characteristics and cardiopulmonary risk factors with aortic and main pulmonary artery (MPA) enlargement by cardiovascular magnetic resonance (CMR). Methods: 1794 Framingham Offspring cohort members (65±9 y, 844 M) underwent axial 2D black-blood T2-weighted thoracoabdominal CMR. MPA and ascending (ASC) and descending (DSC) thoracic aortic diameters were measured at MPA-bifurcation level, abdominal (ABD) aortic diameter at 5 mm above renal artery origins. We assessed relationship of arterial diameters to height (HT) and body surface area (BSA) using Pearson correlation and determined sex-specific 90th percentile cutpoints (p90) for ASC, DSC, ABD, and MPA in a referent group free of obesity (BMI≥30), emphysema, myocardial infarction, heart failure, and any history of hypertension (HTN) or smoking. For the overall study sample, multivariable logistic regression was used to determine the association of high (≥p90) vessel diameters with the above risk factors and age, sex and pack-years smoked. Results: 370 Offspring (157 M) met referent-group criteria. In men neither HT nor BSA correlated with aortic diameter. In women DSC, ABD and MPA correlated with HT and BSA (r=0.14 - 0.25, all p≤0.045), but BSA-indexation gave inverse correlations with HT and BSA (all p&lt;0.0001); HT-indexation gave inverse correlations with HT (all p≤0.045). Thus we used unindexed p90 cutpoints of (M,W): ASC=34.9, 31.8mm; DTA=25.3, 22.7mm; ABD=20.0, 17.3mm; MPA=26.6, 24.2mm. Prevalence of and MV-adjusted odds ratios for high diameter are in the Table (N=1794). Obesity was globally and most strongly associated with overall vessel enlargement. ABD enlargement was associated with total pack-years, but not with positive smoking history. Conclusions: ABD enlargement was slightly more prevalent in women. In both sexes MPA and general aortic enlargement are associated with greater age and obesity, but smoking (as pack years) was associated with ABD enlargement only and HTN with the thoracic aorta only.

Analysis of input-output relationships of CPG elements and their contributions to rhythmic output

We use the dynamic clamp technique [1] to explore how synaptic input patterns affect motor output (see Figure ​Figure1A).1A). We show that leech motor neuron intrinsic properties make a contribution to their output phasing. Then, we show that leech motor neurons receiving the same complement of synaptic inputs can still be organized into a coordinated motor pattern given that a gradient of synaptic strengths exists and that the premotor interneurons fire at different times [2]. In both of these cases, measuring motor neuron responses provides a direct assay for how premotor input patterns produce stereotyped motor output. We are currently extending this analysis to the crayfish swimmeret system, a system in which four segmental oscillators are interconnected by coordinating interneurons to produce a metachronal wave of swimmeret movements [3]. In this system, ascending (ASC) and descending (DSC) coordinating interneurons (see Figure ​Figure1B)1B) encode salient features about the activity pattern of their home segment and are exported (via spikes) to other segmental oscillators. Interestingly, when the system is driven across periods by different concentrations of neuromodulators, the number of spikes of a given coordinating interneuron remains constant although their duty cycles change. We are currently building a single-compartment, conductance-based model of the ASC and DSC coordinating neurons, with the goal of understanding how these coordinating neurons encode information in their home modules and how this encoding can be modulated when the swimmeret system is driven at different periods. Figure 1 Circuit diagrams and rhythmic motor output from the leech heartbeat central pattern generator (A) and the crayfish swimmeret system (B). A, left: Heart (HE) motor neurons in segments 8 and 12 both receive synaptic input from premotor hear (HN) interneurons ...

Rehidratación posejercicio: La forma de distribuir la ingesta de un volumen constante de líquido no altera su conservación

Propósito:evaluar la efectividad de tres protocolos de ingesta de un volumen de bebida deportiva, en la rehidratación posejercicio, según la capacidad de conservar el líquido ingerido dentro del cuerpo. Metodología: en tres días distintos separados por una semana, 11 hombres sanos, físicamente activos, de 21±2 años, 68.7±9.0 kg de peso y 1.72±0.05 m de estatura fueron deshidratados mediante ejercicio al 1.97%±0.20 (media±D.E) del peso corporal, en un cuarto de ambiente controlado (aproximadamente a 32úC y 60% hr). Posteriormente bebieron un volumen de bebida deportiva, equivalente al 120% del peso perdido cada media hora durante hora y media, según uno de tres protocolos de ingesta (asignados aleatoriamente): (IG) porciones iguales (tres porciones equivalentes cada una a 40% del peso perdido), (AS) ascendente (porciones de 25, 40 y 55%) y (DES) descendente (porciones de 55, 40 y 25%). Luego se recogió la orina cada 30 minutos durante tres horas para medir su volumen. Se utilizaron ANOVAs de medidas repetidas para analizar los resultados obtenidos. Resultados: no hubo interacción entre el protocolo de ingesta y el tiempo sobre los volúmenes parciales de orina (p=.119). Tampoco se observó un efecto del protocolo de ingesta sobre el volumen total de orina (IG=670±278 mL, AS=649±184 mL, DES=750±421 mL; p=.609), ni en el porcentaje de conservación del líquido (IG=59.0±16.1%, AS=59.7±13.7%, DES=54.9±19.9%; p=.835). Conclusión: la distribución de un volumen constante de bebida deportiva en tres protocolos distintos de rehidratación posejercicio no produjo diferencias significativas en el volumen de orina, ni en la conservación del líquido ingerido.

Postoperative Complications and Survival after Enterolith Removal from the Ascending or Descending Colon in Horses

To compare incidence of postoperative complications and survival of horses that had surgery for enterolithiasis of the ascending (AC) or descending (DC) colon. Case series Horses (n=236) that had celiotomy for AC (n=97) or DC (n=139) enterolithiasis. Medical records (1999-2005) were reviewed for signalment, presenting clinical signs, surgical findings, postoperative complications, and short-term survival until discharge. Information on performance and survival > or = 1 year was obtained by telephone or mailed questionnaire. Number of postoperative complications did not differ between groups (P=.76). The most frequently identified short-term complications for all horses were incisional problems, gastric ulceration, ileus, diarrhea, fever, and anorexia. Horses with DC enteroliths had a significantly higher incidence of anorexia (P=.04) and fever (P=.01). The most common complications after hospital discharge were incisional problems, laminitis, weight loss, and colic. Although more DC horses were euthanatized intraoperatively (P=.02), no differences were detected for horses that survived until discharge (P=.18) or > or = 1 year after discharge (P=.47). Number or type of postsurgical complications or survival after surgery was not influenced by enterolith location and horses have a favorable prognosis for long-term survival after enterolith removal, regardless of site of obstruction in the colon. Incidence of postoperative complications and survival are not affected by the site of enterolith obstruction in the colon.

Vibratory interneurons in the non-hearing cave cricket indicate evolutionary origin of sound processing elements in Ensifera

Tympanal hearing organs in the front tibiae of ensiferan insects supposedly evolved from vibration-sensitive tibial organs (TO), like those in the cave cricket Troglophilus neglectus (Rhaphidophoridae). If this is true, one expects to find interneurons in the cave cricket that are homologous to auditory neurons from hearing Ensifera. Therefore, we examined the central projections of the foreleg TO of the cave cricket, as well as morphology and response properties of interneurons responding to foreleg vibration. Sensory axons of the TO adjoined to the “tympanal nerve” terminate in the equivalent portion of the ring tract neuropile in the prothoracic ganglion as corresponding receptors of crickets and weta. We found nine putatively homologous elements to sound- and/or vibration-sensitive interneurons of Ensifera – one local neuron (unpaired median, DUM), three T-fibres (TN), three descending (DN) and two ascending neurons (AN). Presumable first-order interneurons arborising in the ring tract correspond to a local auditory DUM cell of bush crickets and to TN1, DN1 and AN2 of various Ensifera, respectively. Homologues of some prominent auditory cells, the “omega” neuron(s) and the ascending neuron 1 (AN1), however, were not found. We conclude that (a) T. neglectus interneurons are morphologically primitive with respect to those of hearing taxa, (b) significant changes in the dendritic structure/synaptic connectivity have taken place during the evolution of the most specialised first-order auditory interneurons of Ensifera, (c) the data do not contradict independent evolution of hearing in Grylloidea and Tettigonoidea. Other interneurons appear morpho-physiologically conserved across hearing and non-hearing species, possibly as a part of a multimodal “alert” system.

Electrophysiologic Identification of the Location of the Colonic Pacemakers in Humans: Further Study

We recently defined the sites of four colonic pacemakers that appear to generate the electric waves assumed to be responsible for the colonic motility. We hypothesized that a dysfunction of one or more of these pacemakers might interfere with the generation of electric waves and the colonic motility. This hypothesis was investigated in the current communication. The tests were performed during the repair of huge incisional hernia of 8 subjects (5 F, 3 M; mean age 42.8 +/- 3.3 SD years). Two electrodes were applied to each of the terminal ileum (TI), cecum (C), and ascending (AC), transverse (TC), descending (DC), and sigmoid (SC) colon. The electric activity of the TI and the various colonic segments was recorded using surface silver-silver chloride electrodes applied to the colon. The site of change of the wave variables between the TI and the C and between the different other colonic segments was determined by changing the position of the electrodes placed over the segments to be examined. Presumably, the sites where the wave variables changed represent the potential location of the pacemakers. We anesthetized these sites individually by injection of 2% Xylocaine, and then recorded the electric activity after 20 min in all the subjects and after 2 h in only 5 subjects. Electric waves in the form of pacesetter and action potentials were recorded from the TI and the colon. The sites of potential pacemakers could be defined at the ileocecal and cecocolonic junctions, at the mid third of the TC, and at the colosigmoid junction. Anesthetization of the cecal pole resulted in disappearance of the cecal electric waves, with persistence of the waves from the other colon segments. Anesthetization of the cecocolonic junction eliminated the electric waves of the AC and the right half of the TC, while the waves in the rest of the colon persisted. The remaining two pacemaker sites produced similar results when anesthetized. The electric waves reappeared after the anesthetic effect had waned. Thus, the colon possesses at least four pacemakers that appear to mediate the colonic motor activity. Individual pacemaker block by anesthetization effected disappearance of electric waves in the relative colonic segment, which reappeared after waning of the anesthetic effect. The disappearance of these waves upon pacemaker anesthetization supports a relationship between the pacemakers at the anesthetized site and the electric waves. The electric waves seem to be generated by these pacemakers. We suggest that colonic inertia, segmental or total, results from the dysfunction of one or more pacemakers, and that an artificial pacemaker could be applied for the treatment of such conditions. These suggestions need to be further studied.

Electrophysiologic Identification of the Location of the Colonic Pacemakers in Humans: Further Study

We recently defined the sites of four colonic pacemakers that appear to generate the electric waves assumed to be responsible for the colonic motility. We hypothesized that a dysfunction of one or more of these pacemakers might interfere with the generation of electric waves and the colonic motility. This hypothesis was investigated in the current communication. The tests were performed during the repair of huge incisional hernia of 8 subjects (5 F, 3 M; mean age 42.8 - 3.3 SD years). Two electrodes were applied to each of the terminal ileum (TI), cecum (C), and ascending (AC), transverse (TC), descending (DC), and sigmoid (SC) colon. The electric activity of the TI and the various colonic segments was recorded using surface silver-silver chloride electrodes applied to the colon. The site of change of the wave variables between the TI and the C and between the different other colonic segments was determined by changing the position of the electrodes placed over the segments to be examined. Presumably, the sites where the wave variables changed represent the potential location of the pacemakers. We anesthetized these sites individually by injection of 2% Xylocaine, and then recorded the electric activity after 20 min in all the subjects and after 2 h in only 5 subjects. Electric waves in the form of pacesetter and action potentials were recorded from the TI and the colon. The sites of potential pacemakers could be defined at the ileocecal and cecocolonic junctions, at the mid third of the TC, and at the colosigmoid junction. Anesthetization of the cecal pole resulted in disappearance of the cecal electric waves, with persistence of the waves from the other colon segments. Anesthetization of the cecocolonic junction eliminated the electric waves of the AC and the right half of the TC, while the waves in the rest of the colon persisted. The remaining two pacemaker sites produced similar results when anesthetized. The electric waves reappeared after the anesthetic effect had waned. Thus, the colon possesses at least four pacemakers that appear to mediate the colonic motor activity. Individual pacemaker block by anesthetization effected disappearance of electric waves in the relative colonic segment, which reappeared after waning of the anesthetic effect. The disappearance of these waves upon pacemaker anesthetization supports a relationship between the pacemakers at the anesthetized site and the electric waves. The electric waves seem to be generated by these pacemakers. We suggest that colonic inertia, segmental or total, results from the dysfunction of one or more pacemakers, and that an artificial pacemaker could be applied for the treatment of such conditions. These suggestions need to be further studied.

Electrophysiologic identification of the location of the colonic pacemakers. A human study.

Colonic inertia, total or segmental, is a known cause of constipation, yet its etiology is poorly understood and its treatment not satisfactory. Although the colonic electric activity has been studied by many investigators, the colonic pacemakers that are assumed to generate the electric waves, are scarcely addressed and their location, to our knowledge, has not been determined. The current communication investigates the possible sites of the colonic pacemakers, aiming at a better understanding of the mechanism of colonic motility and its disorders, notably colonic inertia. The tests were performed during the repair of huge incisional hernia in 12 subjects (mean age 37.7 +/- 10.2 years, 7 women). Monopolar silver-silver chloride electrodes were applied to the terminal ileum (TI) and cecum (C), and to the ascending (AC), transverse (TC), descending (DC) and sigmoid colon (SC); they were fixed by electrode gel to the ileal and colonic serosa. The electric activity of each of the TI, C, AC, TC, DC and SC was recorded. Electric waves in the form of slow waves or pacesetter potentials and action potentials were recorded from the TI and colon. Differences in the frequency, amplitude and conduction velocity of the waves occurred between the TI and the various segments of the colon. The change in the wave variables between the TI and C occurred at the ileocecal junction, between the C and AC at the cecocolonic junction, the AC and TC at the mid third of the TC and the DC and SC at the colosigmoid junction. The colonic electric waves are suggested to be generated by at least 4 pacemakers, which are presumably located at the ileocecal junction, the cecocolonic junction, the mid third of TC and at the colosigmoid junction. The electric waves appear to be responsible for conducting the colonic motor activity. We postulate that disordered colonic pacemakers may produce segmental or total colonic inertia, a proposition that needs further investigation.

Frequency dependence of long-term potentiation and depression in the dentate gyrus of the freely moving rat.

Long-term potentiation (LTP) or long-term depression (LTD) can be produced in the dentate gyrus (DG) of the hippocampus with high-or low-frequency stimulation trains, respectively. Although LTP can be elicited in a variety of preparations, we know of no reports of LTD unaccompanied by seizure activity in the awake rat. In this experiment, test pulses at alternating high (95% of maximum response) and moderate (50-75% of maximum) intensities were presented at 0.05 Hz to the perforant path of freely moving rats in order to assess changes in DG population spike amplitude. Trains were delivered at 10-min intervals, and intratrain frequency was adjusted either upward from 3 Hz or downward from 400 Hz until all subjects had received three consecutive tetani at each of 3, 6, 12.5, 25, 50, 100, 200, and 400 Hz. Potentiation was observed at high frequencies regardless of whether ascending (ASC) or descending (DES) test order was used. Depression occurred at low frequencies, but only in ASC rats. The LTD observed in this preparation was not very robust and was clearly seen only when moderate-intensity test pulses were used. The threshold frequency (at which depression gives way to potentiation) was approximately 6-9 Hz for DES rats but was 100-120 Hz for ASC animals. Prior stimulation therefore affected the response to subsequent trains. These results are generally consistent with the hypothesis of a variable threshold for LTP induction. Our findings can also be explained by postulating a wide "labile range" at moderate frequencies within which no plastic changes occur.

Frequency dependence of long‐term potentiation and depression in the dentate gyrus of the freely moving rat

Long-term potentiation (LTP) or long-term depression (LTD) can be produced in the dentate gyrus (DG) of the hippocampus with high- or low-frequency stimulation trains, respectively. Although LTP can be elicited in a variety of preparations, we know of no reports of LTD unaccompanied by seizure activity in the awake rat. In this experiment, test pulses at alternating high (95% of maximum response) and moderate (50–75% of maximum) intensities were presented at 0.05 Hz to the perforant path of freely moving rats in order to assess changes in DG population spike amplitude. Trains were delivered at 10-min intervals, and intratrain frequency was adjusted either upward from 3 Hz or downward from 400 Hz until all subjects had received three consecutive tetani at each of 3, 6, 12.5, 25, 50, 100, 200, and 400 Hz. Potentiation was observed at high frequencies regardless of whether ascending (ASC) or descending (DES) test order was used. Depression occurred at low frequencies, but only in ASC rats. The LTD observed in this preparation was not very robust and was clearly seen only when moderate-intensity test pulses were used. The threshold frequency (at which depression gives way to potentiation) was approximately 6–9 Hz for DES rats but was 100–120 Hz for ASC animals. Prior stimulation therefore affected the response to subsequent trains. These results are generally consistent with the hypothesis of a variable threshold for LTP induction. Our findings can also be explained by postulating a wide “labile range” at moderate frequencies within which no plastic changes occur. © 1996 Wiley-Liss, Inc.

Fluid loading of the human colon: Effects on segmental transit and stool composition

Background: Because segmental storage by the colon is relevant to diarrheal states, we quantified colonic transit in 13 healthy volunteers. Methods: We infused radiolabelled liquids and solids into the cecum. Gamma camera images were obtained for 48 hours and counts measured in ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colons. Bowel movements were scored for consistency and stool outputs of isotopes were quantified. Results: No volunteers developed diarrhea. Times for isotopes to traverse AC and TC were shorter with rapid infusions (P < 0.001). Counts remaining in AC and TC were also correlated with infusion volumes for 9 hours but not thereafter. Solids were initially delayed in AC but solids and liquids were stored equally in TC. Transit through DC was rapid, but RS stored contents for many hours. First appearance of counts in stools and total counts excreted after 48 hours were not dependent on the infusion rate. Fecal consistency and water content correlated significantly with colonic transit times. Conclusions: Fluids moved ahead of solids in the AC, but liquids and solids were stored equally in the TC. The DC acted mainly as a conduit during fluid overload but the RS stored both isotopes extensively. Stool consistency was a valid reflection of total colonic transit.