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Biomolecules Jun 2023As understanding their pathogenesis remains elusive, both endometriosis and adenomyosis are often referred to as "enigmatic diseases". The uncertainty and heightened... (Review)
Review
As understanding their pathogenesis remains elusive, both endometriosis and adenomyosis are often referred to as "enigmatic diseases". The uncertainty and heightened interest are reflected in the range of expressed views and opinions. There is a sense of urgency because of the entailed patient suffering. The plethora of opinions calls for a critical analysis of proposed theories, both old and new. A series of papers published since 2009 proposed that both endometriosis and adenomyosis originate from the same aberrations occurring within the uterus. This came to be recognized as the tissue injury and repair theory, and the newly coined term "archimetrosis" posits that the two diseases share the same origin. While the theory opens an interesting channel for exploration, its claim as a unifying theory necessitates a critical appraisal. We, thus, undertook this review of the theory and analyzed its underpinnings based on a comprehensive review of the literature. Our appraisal indicates that the theory is open to a range of criticisms. Chief among these is the need for confirmatory evidence of features of abnormal uterine contractility and the lack of data addressing the question of causality. In addition, the theory has, as yet, no supporting epidemiological evidence, which is a major weakness. The theory suffers as it is not open to the test of falsifiability, and it lacks the ability to make useful predictions. It has not addressed the questions, such as why only a small percentage of women develop adenomyosis or endometriosis, given the ubiquity of uterine peristalsis. On the other hand, the triggers and prevention of hyper- or dys-peristalsis become critical to a theory of causation. We conclude that additional supportive evidence is required for the theory to be accepted.
Topics: Female; Humans; Adenomyosis; Endometriosis; Uterus
PubMed: 37371555
DOI: 10.3390/biom13060975 -
American Journal of Physiology.... Feb 2021The goal of this study was to conceptualize and compute measures of "mechanical work" done by the esophagus using data generated during functional lumen imaging probe...
The goal of this study was to conceptualize and compute measures of "mechanical work" done by the esophagus using data generated during functional lumen imaging probe (FLIP) panometry and compare work done during secondary peristalsis among patients and controls. Eighty-five individuals were evaluated with a 16-cm FLIP during sedated endoscopy, including asymptomatic controls ( = 14) and those with achalasia subtypes I, II, and III ( = 15, each); gastroesophageal reflux disease (GERD; = 13); eosinophilic esophagitis (EoE; = 9); and systemic sclerosis (SSc; = 5). The FLIP catheter was positioned to have its distal segment straddling the esophagogastric junction (EGJ) during stepwise distension. Two metrics of work were assessed: "active work" (during bag volumes ≤ 40 mL where contractility generates substantial changes in lumen area) and "work capacity" (for bag volumes ≥ 60 mL when contractility cannot substantially alter the lumen area). Controls showed median [interquartile range (IQR)] of 7.3 (3.6-9.2) mJ of active work and 268.6 (225.2-332.3) mJ of work capacity. Patients with all achalasia subtypes, GERD, and SSc showed lower active work done than controls ( ≤ 0.003). Patients with achalasia subtypes I and II, GERD, and SSc had lower work capacity compared with controls ( < 0.001, 0.004, 0.04, and 0.001, respectively). Work capacity was similar between controls and patients with achalasia type III and EoE. Mechanical work of the esophagus differs between healthy controls and patient groups with achalasia, EoE, SSc, and GERD. Further studies are needed to fully explore the utility of this approach, but these work metrics would be valuable for device design (artificial esophagus), to measure the efficacy of peristalsis, to gauge the physiological state of the esophagus, and to comment on its pumping effectiveness. Functional lumen imaging probe (FLIP) panometry assesses esophageal response to distension and provides a simultaneous assessment of pressure and dimension during contractility. This enables an objective assessment of "mechanical work" done by the esophagus. Eighty-five individuals were evaluated, and two work metrics were computed for each subject. Controls showed greater values of work compared with individuals with achalasia, gastroesophageal reflux disease (GERD), and systemic sclerosis (SSc). These values can quantify the mechanical behavior of the distal esophagus and assist in the estimation of muscular integrity.
Topics: Adult; Aged; Case-Control Studies; Esophageal Achalasia; Esophagus; Female; Gastroesophageal Reflux; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Peristalsis; Pressure; Scleroderma, Systemic
PubMed: 33174457
DOI: 10.1152/ajpgi.00324.2020 -
Neurogastroenterology and Motility Dec 2021Constipation is a gastrointestinal symptom with high incidence rate and large number of patients. It is becoming one of the urgent medical problems. Poor intestinal...
BACKGROUND
Constipation is a gastrointestinal symptom with high incidence rate and large number of patients. It is becoming one of the urgent medical problems. Poor intestinal motility is one of the important causes of constipation. Current drug treatments for constipation are associated with many side effects; thus, it is necessary to study more effective treatment methods and potential mechanism.
METHODS
A zebrafish model of intestinal motility obstruction was established by loperamide hydrochloride to evaluate the effect of probiotic, food ingredients, and combination on intestinal peristalsis according to intestinal peristalsis frequency counts. The gastrointestinal survival ability of the best probiotics was evaluated by surface hydrophobicity, self-aggregation, acid and bile salt tolerance, and gastrointestinal transit tolerance. Interactions between probiotics and food ingredients were studied in vivo and in vitro. The expression of 5-HT was detected by ELISA and fluorescence immunoassay, and 5-HT related genes were detected by RT-PCR.
KEY RESULTS
We obtained the probiotics, food ingredients, and combination that effectively promoted intestinal peristalsis, X11 and YRL577, P. persica and KGM, KGM + X11, respectively. Both KGM and P. persica promoted colonization of probiotics in vivo. KGM + X11 could effectively promote the increase in 5-HT synthesis in zebrafish via up-regulating gene expression of TPH-1, TPH-2, and 5-HT and down-regulating gene expression of SERT. The specific in-depth mechanism needs further study.
CONCLUSIONS AND INFERENCES
The combinations of KGM with X11 effectively promoted intestinal peristalsis. We provide a theoretical basis for new modalities that can promote intestinal peristalsis and alleviate constipation.
Topics: Animals; Constipation; Disease Models, Animal; Gastrointestinal Motility; Intestinal Obstruction; Intestines; Lacticaseibacillus paracasei; Mannans; Probiotics; Serotonin; Zebrafish
PubMed: 34337833
DOI: 10.1111/nmo.14196 -
Scientific Reports Dec 2020The flow inside the perivascular space (PVS) is modeled using a first-principles approach in order to investigate how the cerebrospinal fluid (CSF) enters the brain...
The flow inside the perivascular space (PVS) is modeled using a first-principles approach in order to investigate how the cerebrospinal fluid (CSF) enters the brain through a permeable layer of glial cells. Lubrication theory is employed to deal with the flow in the thin annular gap of the perivascular space between an impermeable artery and the brain tissue. The artery has an imposed peristaltic deformation and the deformable brain tissue is modeled by means of an elastic Hooke's law. The perivascular flow model is solved numerically, discovering that the peristaltic wave induces a steady streaming to/from the brain which strongly depends on the rigidity and the permeability of the brain tissue. A detailed quantification of the through flow across the glial boundary is obtained for a large parameter space of physiologically relevant conditions. The parameters include the elasticity and permeability of the brain, the curvature of the artery, its length and the amplitude of the peristaltic wave. A steady streaming component of the through flow due to the peristaltic wave is characterized by an in-depth physical analysis and the velocity across the glial layer is found to flow from and to the PVS, depending on the elasticity and permeability of the brain. The through CSF flow velocity is quantified to be of the order of micrometers per seconds.
Topics: Animals; Arteries; Brain; Glymphatic System; Peristalsis; Permeability; Pressure
PubMed: 33273489
DOI: 10.1038/s41598-020-77787-4 -
Biofabrication Oct 2021Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal...
Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal organoid culture. Here, we present a method to model the peristalsis for human colon tumor organoids on a microfluidic chip. The chip contains hundreds of lateral microwells and a surrounding pressure channel. Human colon tumor organoids growing in the microwell were cyclically contracted by pressure channel, mimicking themechano-stimulus by intestinal muscles. The chip allows the control of peristalsis amplitude and rhythm and the high throughput culture of organoids simultaneously. By applying 8% amplitude with 8 ∼ 10 times min, we observed the enhanced expression of Lgr5 and Ki67. Moreover, ellipticine-loaded polymeric micelles showed reduced uptake in the organoids under peristalsis and resulted in compromised anti-tumor efficacy. The results indicate the importance of mechanical stimuli mimicking the physiological environment when usingmodels to evaluate nanoparticles. This work provides a method for attaining more reliable and representative organoids models in nanomedicine.
Topics: Colonic Neoplasms; Humans; Lab-On-A-Chip Devices; Microfluidics; Organoids; Peristalsis; Tumor Microenvironment
PubMed: 34638112
DOI: 10.1088/1758-5090/ac2ef9 -
Gastro Hep Advances 2023High-resolution manometry, Chicago Classification v4.0, the functional lumen imaging probe, Panometry, and peroral endoscopic myotomy (POEM) are all now integral parts...
High-resolution manometry, Chicago Classification v4.0, the functional lumen imaging probe, Panometry, and peroral endoscopic myotomy (POEM) are all now integral parts of the landscape for managing achalasia or, more precisely, achalasia-like syndromes. This narrative review examines the impact of these innovations on the management of achalasia-like syndromes. High-resolution manometry was the disruptive technology that prompted the paradigm shift to thinking of motility disorders as patterns of obstructive physiology involving the esophagogastric junction and/or the distal esophagus rather than as siloed entities. An early observation was that the cardinal feature of achalasia-impaired lower esophageal sphincter relaxation-can occur in several subtypes: without peristalsis, with pan-esophageal pressurization, with premature (spastic) distal esophageal contractions, or even with preserved peristalsis (esophagogastric junction outlet obstruction). Furthermore, there being no biomarker for achalasia, no manometric pattern is perfectly sensitive or specific for 'achalasia' and there is also no 'gold standard' for the diagnosis. Consequently, complimentary physiological testing with a timed barium esophagram or functional lumen imaging probe are employed both to improve the detection of patients likely to respond to treatments for 'achalasia' and to characterize other syndromes also likely to benefit from achalasia therapies. These findings have become particularly relevant with the development of a minimally invasive technique for performing a tailored esophageal myotomy, POEM. Now and in the future, optimal achalasia management is to render treatment in a phenotype-specific manner, that is, POEM calibrated in a patient-specific manner for obstructive physiology including the distal esophagus and more conservative strategies such as a short POEM or pneumatic dilation for obstructive physiology limited to the lower esophageal sphincter.
PubMed: 37503535
DOI: 10.1016/j.gastha.2023.02.001 -
Neurogastroenterology and Motility Nov 2021High amplitude peristaltic esophageal contractions, that is, nutcracker esophagus, were originally described in association with "angina-like pain" of esophageal origin....
INTRODUCTION
High amplitude peristaltic esophageal contractions, that is, nutcracker esophagus, were originally described in association with "angina-like pain" of esophageal origin. However, significant number of nutcracker patients also suffer from dysphagia. High-resolution esophageal manometry (HRM) assesses only the contraction phase of peristalsis. The degree of esophageal distension during peristalsis is a surrogate of relaxation and can be measured from the intraluminal esophageal impedance measurements.
AIMS
Determine the amplitude of distension and temporal relationship between distension and contraction during swallow-induced peristalsis in nutcracker patients.
METHODS
HRM impedance (HRMZ) studies were performed and analyzed in 24 nutcracker and 30 normal subjects in the Trendelenburg position. A custom-built software calculated the numerical data of the amplitudes of distension and contraction, the area under the curve (AUC) of distension and contraction, and the temporal relationship between distension and contraction.
RESULTS
In normal subjects, the distension peaks similar to contraction traverse sequentially the esophagus. The amplitude of contraction is greater in the nutcracker esophagus but the amplitude of distension and area under the curve of distension are smaller in patients compared to controls. Distension peaks are aligned closely with contraction in normal subjects, but in patients, the bolus travels faster to the distal esophagus, resulting in a smaller time interval between the onset of swallow and distension peak. Receiver operative characteristics (ROC) curve reveals high sensitivity and specificity of the above parameters in patients.
CONCLUSION
Abnormalities in the distension phase of peristalsis are a possible mechanism of dysphagia in patients with nutcracker esophagus.
Topics: Adult; Aged; Deglutition Disorders; Esophageal Motility Disorders; Female; Humans; Male; Manometry; Middle Aged; Muscle Contraction; Peristalsis; ROC Curve; Young Adult
PubMed: 33818858
DOI: 10.1111/nmo.14138 -
Cell Reports Mar 2020Peristalsis is indispensable for physiological function of the gut. The enteric nervous system (ENS) plays an important role in regulating peristalsis. While the neural...
Peristalsis is indispensable for physiological function of the gut. The enteric nervous system (ENS) plays an important role in regulating peristalsis. While the neural network regulating anterograde peristalsis, which migrates from the oral end to the anal end, is characterized to some extent, retrograde peristalsis remains unresolved with regards to its neural regulation. Using forward genetics in zebrafish, we reveal that a population of neurons expressing a hyperpolarization-activated nucleotide-gated channel HCN4 specifically regulates retrograde peristalsis. When HCN4 channels are blocked by an HCN channel inhibitor or morpholinos blocking the protein expression, retrograde peristalsis is specifically attenuated. Conversely, when HCN4(+) neurons expressing channelrhodopsin are activated by illumination, retrograde peristalsis is enhanced while anterograde peristalsis remains unchanged. We propose that HCN4(+) neurons in the ENS forward activating signals toward the oral end and simultaneously stimulate local circuits regulating the circular muscle.
Topics: Animals; Animals, Genetically Modified; Gastrointestinal Motility; Gastrointestinal Tract; Gene Expression Regulation; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Larva; Morpholinos; Neurons; Optogenetics; Peristalsis; Serotonin; Zebrafish
PubMed: 32130893
DOI: 10.1016/j.celrep.2020.02.024 -
Proceedings of the National Academy of... May 2022The peristaltic reflex is a fundamental behavior of the gastrointestinal (GI) tract in which mucosal stimulation activates propulsive contractions. The reflex occurs by...
The peristaltic reflex is a fundamental behavior of the gastrointestinal (GI) tract in which mucosal stimulation activates propulsive contractions. The reflex occurs by stimulation of intrinsic primary afferent neurons with cell bodies in the myenteric plexus and projections to the lamina propria, distribution of information by interneurons, and activation of muscle motor neurons. The current concept is that excitatory cholinergic motor neurons are activated proximal to and inhibitory neurons are activated distal to the stimulus site. We found that atropine reduced, but did not block, colonic migrating motor complexes (CMMCs) in mouse, monkey, and human colons, suggesting a mechanism other than one activated by cholinergic neurons is involved in the generation/propagation of CMMCs. CMMCs were activated after a period of nerve stimulation in colons of each species, suggesting that the propulsive contractions of CMMCs may be due to the poststimulus excitation that follows inhibitory neural responses. Blocking nitrergic neurotransmission inhibited poststimulus excitation in muscle strips and blocked CMMCs in intact colons. Our data demonstrate that poststimulus excitation is due to increased Ca2+ transients in colonic interstitial cells of Cajal (ICC) following cessation of nitrergic, cyclic guanosine monophosphate (cGMP)-dependent inhibitory responses. The increase in Ca2+ transients after nitrergic responses activates a Ca2+-activated Cl− conductance, encoded by Ano1, in ICC. Antagonists of ANO1 channels inhibit poststimulus depolarizations in colonic muscles and CMMCs in intact colons. The poststimulus excitatory responses in ICC are linked to cGMP-inhibited cyclic adenosine monophosphate (cAMP) phosphodiesterase 3a and cAMP-dependent effects. These data suggest alternative mechanisms for generation and propagation of CMMCs in the colon.
Topics: Colon; Gastrointestinal Motility; Interstitial Cells of Cajal; Myocytes, Smooth Muscle; Peristalsis
PubMed: 35446689
DOI: 10.1073/pnas.2123020119 -
Neurogastroenterology and Motility Aug 2021Esophageal hypercontractility (EHC) is considered a major esophageal motor disorder of unclear etiology. Different mechanisms have been proposed, including an imbalance...
BACKGROUND
Esophageal hypercontractility (EHC) is considered a major esophageal motor disorder of unclear etiology. Different mechanisms have been proposed, including an imbalance in inhibitory and excitatory esophageal innervation. We hypothesized that patients with EHC suffer from cholinergic hyperactivity.
AIM
To interrogate the excitatory and inhibitory neurotransmission in EHC by assessing the esophageal motor response to atropine (ATR) and cholecystokinin (CCK), respectively, in EHC patients.
METHOD
We retrospectively reviewed patients who underwent high-resolution manometry (HRM) with pharmacologic challenge in a tertiary referral center between 2007 and 2017. We identified 49 EHC patients who were categorized based on frequency of hypercontractile peristaltic sequence into "frequent" and "infrequent" and motility diagnosis groups. Deglutitive pressure metrics and esophageal motor responses to ATR (12 mcg/kg iv) and CCK (40 ng/kg iv) were analyzed across groups.
RESULTS
Atropine abolished hypercontractility across all groups studied, converting nearly half of patients to a motor pattern of ineffective esophageal motility. Abnormal CCK responses primarily occurred in the patient groups with concomitant outflow obstruction.
CONCLUSIONS
Hypercontractility is cholinergically mediated in all esophageal motor disorders. Most patients with isolated EHC appear to have excessive cholinergic drive, rather than loss of inhibitory innervation, and might be candidates for treatment with anticholinergic agents.
Topics: Aged; Atropine; Esophageal Motility Disorders; Esophagus; Female; Humans; Male; Manometry; Middle Aged; Muscarinic Antagonists; Muscle Contraction; Peristalsis; Retrospective Studies
PubMed: 33185322
DOI: 10.1111/nmo.14017