Gastrointestinal Motility Disorders Research Articles

Insights into the current state of knowledge, practice, and attitudes of physicians regarding gastrointestinal motility disorders in Egypt

BackgroundGastrointestinal (GI) motility disorders are common in clinical settings, but physicians still lack sufficient understanding and effective management of these conditions.MethodsThis research assessed Egyptian physicians’ knowledge, practices, and attitudes towards GI motility disorders. A cross-sectional survey employing a self-administered questionnaire was carried out among physicians in Egypt. The questionnaire addressed various aspects of physicians’ understanding, practices, and attitudes regarding GI motility disorders. Data analysis was conducted using descriptive statistics and presented as frequencies and percentages.ResultsA total of 462 physicians took part in the study. Although nearly two-thirds of them knew about GI motility studies, a notable proportion lacked adequate knowledge about GI motility disorders. Notably, 84.2% correctly identified dysphagia as a critical symptom suggestive of an upper GI motility disorder. However, 13.4% incorrectly linked hematemesis with an upper GI motility disorder, and 16.7% expressed uncertainty. In terms of practice, around half of the participants encountered a small number of patients with GI motility disorders (less than 5 per week or even fewer). Only 29.7% felt confident in managing patients with motility disorders. Most participating physicians expressed a willingness to participate in training programs focused on motility disorders.ConclusionsThis study underscores a knowledge gap among Egyptian physicians concerning GI motility disorders. It suggests the necessity of tailored education and training programs to improve their competency and practice in this domain.

Electroceuticals and Magnetoceuticals in Gastroenterology

In the realm of gastroenterology, the inadequacy of current medical treatments for gastrointestinal (GI) motility disorders and inflammatory bowel disease (IBD), coupled with their potential side effects, necessitates novel therapeutic approaches. Neuromodulation, targeting the nervous system’s control of GI functions, emerges as a promising alternative. This review explores the promising effects of vagal nerve stimulation (VNS), magnetic neuromodulation, and acupuncture in managing these challenging conditions. VNS offers targeted modulation of GI motility and inflammation, presenting a potential solution for patients not fully relieved from traditional medications. Magnetic neuromodulation, through non-invasive means, aims to enhance neurophysiological processes, showing promise in improving GI function and reducing inflammation. Acupuncture and electroacupuncture, grounded in traditional medicine yet validated by modern science, exert comprehensive effects on GI physiology via neuro-immune-endocrine mechanisms, offering relief from motility and inflammatory symptoms. This review highlights the need for further research to refine these interventions, emphasizing their prospective role in advancing patient-specific management strategies for GI motility disorders and IBD, thus paving the way for a new therapeutic paradigm.

Effects of Saikosaponin D on Apoptosis, Autophagy, and Morphological Structure of Intestinal Cells of Cajal with Functional Dyspepsia.

Functional dyspepsia (FD) is one of the most common gastrointestinal diseases, with a global prevalence of 10%-30%. However, the specific pathogenesis of FD has not yet been determined. As such, the aim of this study was to investigate the effects of saikosaponin D (SSD) administration on the apoptosis, autophagy, and morphological structure of the intestinal cells of Cajal (ICCs) in FD. Methods：A rat model of FD was constructed by stimulating the rat tail with a sponge clamp at one-third of the distal tail length. An autophagy model was constructed for ICCs using glutamate. The apoptosis rate in each group of cells was determined using flow cytometry. The expressions of ghrelin and substance P (SP) were detected using ELISA. The body weight and food intake of male and female rats in the SSD group were consistently higher than those in the model group. The SSD group showed substantial improvement compared with the model group, with no inflammatory cell infiltration and normal gastric mucosal structures. After intervention with SSD, the ultrastructure of the ICCs considerably improved and was clear. Compared with the model group, the expressions of LC3 I/II, ghrelin, and SP proteins in the SSD group were significantly upregulated, and the apoptosis rate was significantly reduced. The administration of SSD improved ICC morphology and structure, inhibited excessive autophagy, and improved FD, a gastrointestinal motility disorder, by regulating ghrelin and SP levels.

Irritable bowel syndrome following infectious COVID-19: East Java, Indonesia, 2023

Irritable bowel syndrome (IBS) is a functional disorder that causes chronic abdominal pain without a known cause. It is a common, chronic gastrointestinal (GI) motility disorder with bothersome symptoms that often lower quality of life and activity. In addition, Patients and healthcare facilities also face significant financial costs. COVID-19 directly damages the digestive system and alters the complex interaction of physical, mental, and social factors that cause digestive problems. SARS-CoV-2 survivors in personal isolation will be examined for IBS prevalence. The dates of this descriptive cross-sectional study are January through April 2023. Rome IV criteria and an online questionnaire were used to confirm the diagnosis of IBS. The principal location where polls have been sent is East Java, Indonesia. The 96 COVID-19 survivors aged 18–60 of both genders was included during self-quarantine. There were 59 females (61.46%) and 37 males (38.54%). The prevalence of IBS was discovered to be 19 (19.79%) among a total of 96 patients. This could be because self-quarantined people have more stable living conditions than hospitalized people. Based on these findings, it is suggested that future research consider gender as the primary proxy for identifying irritable bowel syndrome (IBS).

Successful Treatment using OMT for Chronic GERD in a Pediatric Patient

Abstract Gastroesophageal Reflux Disease (GERD) is a highly prevalent gastrointestinal motility disorder affecting 10% to 20% of children in the United States. Many patients affected by this disorder are medically managed with proton pump inhibitors (PPI) and H2 receptor antagonists for prolonged durations. Here we present a pediatric patient with GERD refractory to chronic use of PPI. The patient received Osteopathic Manipulative Treatment (OMT) and had close follow-ups over 5 years. The patient reported significant relief in symptoms and improved daily performance within weeks of treatment. His symptoms are now being fully controlled by OMT without regular medication. This case report illustrates the advantages of utilizing OMT in the pediatric population.

Capsules for the Diagnosis and Treatment of Gastrointestinal Motility Disorders- A Game Changer.

Over the last few decades, there have been remarkable strides in endoscopy and radiological imaging that have advanced gastroenterology. However, the management of neurogastroenterological disorders has lagged behind, in part handicapped by the use of catheter-based manometry that is both non-physiological and uncomfortable. The advent of capsule technology has been a game changer for both diagnostic and therapeutic applications. Here, we discuss several capsule devices that are available or under investigation. There are three technologies that are FDA approved. Wireless motility capsule measures pH and pressure and provides clinically impactful information regarding gastric, small intestine and colonic transit, without radiation that has been demonstrated to guide management of gastroparesis, dyspepsia and constipation. Wireless ambulatory pH monitoring capsule is currently the gold standard for assessing gastroesophageal acid reflux. In the therapeutics arena, an orally ingested vibrating capsule has been recently FDA approved for the treatment of chronic constipation, supported by a robust phase 3 clinical trial which showed significant improvement in constipation symptoms and quality of life. There are several capsules currently under investigation. Smart capsule bacterial detection system and Capscan® are capsules that can sample fluid in the small or large bowel and provide microbiome analysis for detection of small intestinal bacterial (SIBO) or fungal overgrowth (SIFO). Another investigational gas sensing capsule analyzing hydrogen, CO2, volatile fatty acids and capsule orientation, can measure regional gut transit time and luminal gas concentrations and assess gastroparesis, constipation or SIBO. Therapeutically, other vibrating capsules are in development. Innovations in capsule technology are poised to transform our ability to investigate gut function physiologically, and non-invasively deliver targeted treatment(s), thereby providing both accurate diagnostic information and luminally-directed, safe therapy.

Tips and Thought Processes to Overcome Difficult Situations in Third Space Endoscopy.

Third space endoscopy (TSE) offers diverse treatment options for a variety of conditions of the gastrointestinal tract and motility disorders. Accuracy and precise dissection have helped treat complex conventional surgeries with TSE. Despite over a decade of its presence, difficult situations are routinely encountered. The first challenging situation is decision-making (before the procedure), the second is tackling procedure-induced pulmonary / insufflation-related adverse events and intra-operative complications (during the procedure), and the third is post-operative complications and morbidity (post-procedure). The performance of TSE procedures is not without risk. Patients should receive enough time to weigh their options, considering that attitudes toward risk impact decision-making. Continuous basic patient monitoring and the micro-movements of endoscopic and electrosurgical equipment is crucial to avoid accidental injury. Anaesthetists should be mindful of anticipated complications and closely monitor, diagnose, and treat them. Demanding situations need careful consideration, problem-solving, or persistence to overcome challenges. This brief review provides inputs on preventing and tackling difficult situations in TSE.

Common Pathophysiological Mechanisms and Treatment of Diabetic Gastroparesis.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.

Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases.

Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques-vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)-as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. Materials and Methods: We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. Results: Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. Conclusions: Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols.

Electroacupuncture ameliorates gastrointestinal dysfunction by modulating DMV cholinergic efferent signals to drive the vagus nerve in p-MCAO rats

BackgroundThe use of proton pump inhibitors in the acute phase of cerebral infarction may lead to adverse long-term outcomes, this study aims to explore the potential of electroacupuncture (EA) in replacing omeprazole in exerting post-stroke gastrointestinal protection. MethodsA permanent middle cerebral artery infarction model was established using the modified Longa thread occlusion technique. Gastrointestinal motility, gastrointestinal mucosal damage, cerebral infarct volume, and alterations in choline acetyltransferase (ChAT)-positive neurons within the dorsal motor nucleus of the vagus nerve (DMV) were assessed after 7 days of EA at Zusanli (ST36) or omeprazole intervention. To evaluate the role of the vagal nerve in mitigating post-stroke gastrointestinal dysfunction, we employed subdiaphragmatic vagotomy and the ChAT-specific inhibitor α-NETA. Additionally, we utilized methyllycaconitine (MLA), a selective inhibitor of the α7-type nicotinic acetylcholine receptor (α7nAChR), and PNU282987, an agonist, to identify the target of EA. ResultsEA restored ChAT neurons lost in the DMV, activated the vagus nerve and conferred cerebroprotection while ameliorating gastrointestinal mucosal injury and gastrointestinal motility disorders. In addition, following the administration of the α7nAChR antagonist, the attenuation of gastric mucosal injury and inflammatory factors induced by EA was hindered, although gastrointestinal motility still exhibited improvement. ConclusionEA at ST36 promotes the restoration of cholinergic signaling in the DMV of stroke-afflicted rats, and its excitation of the vagal nerve inhibits gastrointestinal inflammation after stroke via α7nAChR, while improvement in gastrointestinal motility could be mediated by other acetylcholine receptors.

Measurement and Analysis of In Vivo Gastroduodenal Slow Wave Patterns Using Anatomically-Specific Cradles and Electrodes.

Bioelectrical 'slow waves' regulate gastrointestinal contractions. We aimed to confirm whether the pyloric sphincter demarcates slow waves in the intact stomach and duodenum. We developed and validated novel anatomically-specific electrode cradles and analysis techniques which enable high-resolution slow wave mapping across the in vivo gastroduodenal junction. Cradles housed flexible-printed-circuit and custom cradle-specific electrode arrays during acute porcine experiments (N = 9; 44.92 kg ± 8.49 kg) and maintained electrode contact with the gastroduodenal serosa. Simultaneous gastric and duodenal slow waves were filtered independently after determining suitable organ-specific filters. Validated algorithms calculated slow wave propagation patterns and quantitative descriptions. Butterworth filters, with cut-off frequencies (0.0167 - 2) Hz and (0.167 - 3.33) Hz, were optimal filters for gastric and intestinal slow wave signals, respectively. Antral slow waves had a frequency of (2.76 ± 0.37) cpm, velocity of (4.83 ± 0.21) mm·s-1, and amplitude of (1.13 ± 0.24) mV, before terminating at the quiescent pylorus that was (46.54 ± 5.73) mm wide. Duodenal slow waves had a frequency of (18.13 ± 0.56) cpm, velocity of (11.66 ± 1.36) mm·s-1, amplitude of (0.32 ± 0.03) mV, and originated from a pacemaker region (7.24 ± 4.70) mm distal to the quiescent zone. Novel engineering methods enable measurement of in vivo electrical activity across the gastroduodenal junction and provide qualitative and quantitative definitions of slow wave activity. The pylorus is a clinical target for a range of gastrointestinal motility disorders and this work may inform diagnostic and treatment practices.

Mesenchymal cells regulate enteric neural crest cell migration via RET-GFRA1b trans-signaling

During early development, the enteric nervous system forms from the migration of enteric neural crest cells (ENCCs) from the foregut to the hindgut, where they undergo proliferation and differentiation facilitated by interactions with enteric mesenchymal cells (EMCs). This study investigates the impact on ENCC migration of EMC-ENCC communication mediated by GFRA1b expressed in EMCs. GFRA1-expressing cells in day 11–12 (E11–12) mouse embryos differentiated into smooth muscle cells from E12 onwards. Observations at E12–13.5 revealed high levels of GFRA1 expression on the anti-mesenteric side of the hindgut, correlating with enhanced ENCC migration. This indicates that GFRA1 in EMCs plays a role in ENCC migration during development. Examining GFRA1 isoforms, we found high levels of GFRA1b, which lacks amino acids 140–144, in EMCs. To assess the impact of GFRA1 isoforms on EMC-ENCC communication, we conducted neurosphere drop assays. This revealed that GFRA1b-expressing cells promoted GDNF-dependent extension and increased neurite density in ENCC neurospheres. Co-culture of ENCC mimetic cells expressing RET and GFRA1a with EMC mimetic cells expressing GFRA1a, GFRA1b, or vector alone showed that only GFRA1b-expressing co-cultured cells sustained RET phosphorylation in ENCC-mimetic cells for over 120 min upon GDNF stimulation. Our study provides evidence that GFRA1b-mediated cell-to-cell communication plays a critical role in ENCC motility in enteric nervous system development. These findings contribute to understanding the cellular interactions and signaling mechanisms that underlie enteric nervous system formation and highlight potential therapeutic targets for gastrointestinal motility disorders.

Хронічна інтестинальна псевдообструкція в дітей (огляд літератури)

Hirschsprung disease and chronic intestinal pseudo-obstruction (CIPO) in children are the most common and severe disorders of gastro-intestinal tract motility. While the problems connected with the Hirschsprung disease widely coverage in native literature, the publications that devoted the CIPO absent. Aim of the study was to analyze the literature data that devoted to the diagnosis and treatment of children with CIPO. Intestinal pseudo-obstruction refers to heterogeneous groups of disorders with a similar phenotypic presentation characterized by obstructive intestinal symptoms in the absence of true anatomical obstruction. CIPO classification based on the primary dysfunction: affected enteral nervous system (neuropathy), affected smooth muscle (myopathy) or interstitial cells Cajal (mesenchymopathy). Besides that, the intestinal pseudo-obstruction is divided into primary and secondary, congenital and acquired, total and segmentary. The main clinical features, methods of investigation in suspected CIPO such as radiological (roentgenography and roentgenoscopy, computed tomography, cine magnetic resonance), endoscopic, manometry, pathohistological, etc. were listed. The main principles of nutrition support, conventional therapy, and surgical management were presented. Conclusions. CIPO is a severe disorder of gastrointestinal motility that caused by various factors, which can be congenital and/or acquired. Diagnosis of CIPO based on the results of clinical, instrumental, and pathohistological investigation. The management of children with CIPO should include nutritional support, conventional therapy, and, for the clear indices, surgical correction. No conflict of interests was declared by the authors.

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate.MethodsA library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone.ResultsAfter screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC.ConclusionCollectively, these findings suggest that domperidone serves as an effective “multi-target” inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Got the Munchies for an Egg Sandwich? The Effects of Cannabis on Bowel Motility and Beyond.

The use of medicinal cannabis has a long history dating back thousands of years. Recent discoveries have shed light on its mechanism of action with the identification of cannabinoid receptors and endocannabinoids, which make up the body's endocannabinoid system. Cannabinoid receptors, particularly the cannabinoid 1 and 2 receptors, play a crucial role in modulating the gut-brain axis and serve as potential therapeutic targets for gastrointestinal motility and inflammatory disorders. With increasing legalization of cannabis and a rising number of users, understanding the effects of cannabis on gut motility is essential for nuclear medicine providers. Although tetrahydrocannabinol, the principal psychoactive constituent of cannabis, may decrease gut motility in experimental settings, it appears to paradoxically improve symptoms in gastroparesis. Treatment effects are difficult to measure given the large number of variables that could significantly alter outcomes, such as cannabinoid type, potency, and route of intake. Another consideration is the highly personalized gut microbiome, which directly interacts with the endocannabinoid system. Further research is required to delineate these multifaceted, complex cannabinoid interactions. The goal of this article is to explore the knowns and unknowns of the impact of cannabis on the alimentary system.

Gene expression level and immunohistochemical localization of cannabinoid and cannabinoid-related receptors in the small intestine of Holstein bulls (Bos taurus taurus)

Abstract The gastrointestinal tract plays a crucial role in nutrient absorption, secretion, and motility, ensuring proper digestion and overall homeostasis. Regulation of this complex system involves the coordination of various communication pathways, including neural and humoral mechanisms. One such mechanism is the endocannabinoid system (ECS), a signalling network comprising endogenous cannabinoids, receptors, and enzymes involved in the regulation of physiological processes in mammals and non-mammalian species. While extensive research has been conducted on the ECS in monogastric animals, limited information is available on its presence and distribution in cattle. This study aimed to investigate the distribution and localization patterns of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) and transient receptor potential vanilloid type 1 (TRPV1) in the bovine small intestine. The study included immunohistochemical analysis of intestinal tissue samples from Polish Holstein-Friesian breed bulls. Gene expression levels of CNR1, CNR2, and TRPV1 genes, encoding CB1R, CB2R, and TRPV1, respectively, were quantified using qPCR analysis. The results showed that all three receptors were expressed in the bovine small intestine, with TRPV1 exhibiting a significant upregulation in the jejunum compared to the duodenum and ileum. Immunoreactivity for CB1R and CB2R was predominantly observed in neurons of the enteric plexuses, while TRPV1 immunolabeling was detected in both enteric neurons and duodenal Brunner’s glands. These findings may establish an anatomical foundation for further investigations, lending support to the potential therapeutic efficacy of cannabinoid receptor agonists in alleviating gastrointestinal motility disorders associated with bovine enteropathies and optimizing milk production in dairy cattle.

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats.

Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal(GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology,Institute of MedicalSciences,Banaras Hindu University, Varanasi,Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.

Gastrointestinal dysmotility in rodent models of Parkinson's disease.

Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying, and chronic constipation. Indeed, strong evidence from studies in humans and animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous system (CNS) could have a major role in the etiology of PD. In fact, misfolded α-synuclein aggregates that form Lewy bodies and neurites, i.e., the histological hallmarks of PD, are detected in the enteric nervous system (ENS) before clinical diagnosis of PD. The aim of the present review is to provide novel insights into the pathogenesis of GI dysmotility in PD, focusing our attention on functional, neurochemical, and molecular alterations in animal models.

Serping1 associated with α-synuclein increase in colonic smooth muscles of MPTP-induced Parkinson’s disease mice

Patients with Parkinson’s disease (PD) have gastrointestinal motility disorders, which are common non-motor symptoms. However, the reasons for these motility disorders remain unclear. Increased alpha-synuclein (α-syn) is considered an important factor in peristalsis dysfunction in colonic smooth muscles in patients with PD. In this study, the morphological changes and association between serping1 and α-syn were investigated in the colon of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced chronic PD model. Increased serping1 and α-syn were noted in the colon of the PD model, and decreased serping1 also induced a decrease in α-syn in C2C12 cells. Serping1 is a major regulator of physiological processes in the kallikrein-kinin system, controlling processes including inflammation and vasodilation. The kinin system also comprises bradykinin and bradykinin receptor 1. The factors related to the kallikrein-kinin system, bradykinin, and bradykinin receptor 1 were regulated by serping1 in C2C12 cells. The expression levels of bradykinin and bradykinin receptor 1, modulated by serping1 also increased in the colon of the PD model. These results suggest that the regulation of increased serping1 could alleviate Lewy-type α-synucleinopathy, a characteristic of PD. Furthermore, this study could have a positive effect on the early stages of PD progression because of the perception that α-syn in colonic tissues is present prior to the development of PD motor symptoms.

The association between oral carbohydrate intake before orthopedic surgery for osteoporotic fractures and outcomes in elderly patients

BackgroundOral carbohydrate (CHO) intake is a safe method with effective clinical results in various surgical patients before surgery. Nevertheless, due to a lack of adequate clinical data, it is not frequently utilized in older patients undergoing orthopedic surgery for osteoporotic fractures (OPFs), especially in China. The purpose of the present study was to examine the relationship between preoperative oral CHO consumption and outcomes in elderly patients undergoing surgical treatment for OPFs.MethodsThis retrospective cohort study was conducted at a single Chinese institution and included a total of 879 elderly patients (median age: 71 years; range: 50–99 years) who underwent OPF surgery. Various exclusion criteria were established as follows: (a) the necessity for urgent surgical intervention; (b) the existence of hypoglycemia, hyperglycemia, or diabetes mellitus with blood glucose levels lower than 2.8 mmol/L; (c) a medical history of gastrointestinal motility disorders or delayed gastric emptying; (d) the utilization of local anesthesia; (e) a Charlson comorbidity index (CCI) score over 2; and (f) an American Society of Anesthesiologists (ASA) score exceeding 3. After propensity score (PS) matching, 264 patients from each cohort were included in the analysis. The primary outcome was the all-cause mortality rate within 60 days post-surgery, while secondary outcomes included the length of hospital stay (LOS), hospitalization costs, intraoperative and postoperative blood transfusions, and the incidence of postoperative nausea and vomiting (PONV) and aspiration. The relationship between preoperative oral CHO intake and outcomes was evaluated using multivariate regression analysis.ResultsAfter PS matching, preoperative oral CHO intake was negatively associated with 60-day mortality in the fully adjusted model (odds ratio 0.35; 95% confidence interval 0.12–0.97; P-value: 0.04). Patients who received preoperative oral CHO intake also had a shorter LOS and lower hospitalization costs than those who did not receive CHO intake. However, none of the models showed a significant association between CHO intake and PONV or blood transfusion risk. Furthermore, no cases of aspiration were observed in either cohort.ConclusionsPreoperative oral CHO intake may be associated with reduced mortality risk and improved outcomes in elderly patients undergoing surgical treatment for OPFs. However, it is important to acknowledge the limitations of our study, including its retrospective nature, potential unmeasured confounding variables, the small sample size, incomplete data on important variables such as duration of surgery and inflammatory markers, and the limited generalizability due to the participation of only one institution. Future research with larger sample sizes and a broader range of events is warranted to validate and enhance the validity of our findings, particularly in assessing long-term results and understanding the underlying mechanisms.