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Journal of Gastrointestinal Surgery :... Jan 2020Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular...
INTRODUCTION
Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown.
METHODS
Male Sprague Dawley rats approximately 3 months old and weighing 300-350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis.
RESULTS
Compared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-β signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-β signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats' ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues.
CONCLUSION
Deposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.
Topics: Animals; Burns; Colon; Disease Models, Animal; Extracellular Matrix Proteins; Fibronectins; Fibrosis; Gastric Emptying; Gastrointestinal Motility; Ileum; Ileus; Inflammation; Intestinal Pseudo-Obstruction; Laminin; Male; Muscle Contraction; Muscle, Smooth; Phosphorylation; Pyloric Antrum; Rats; Rats, Sprague-Dawley; Signal Transduction; Stomach
PubMed: 31637625
DOI: 10.1007/s11605-019-04400-z -
Journal of Vascular Surgery Sep 1998A major gastrointestinal complication (GIC) after aortic surgery may be disastrous, but these complications have received scant attention. This study was performed to...
BACKGROUND AND PURPOSE
A major gastrointestinal complication (GIC) after aortic surgery may be disastrous, but these complications have received scant attention. This study was performed to determine the risk factors, associated events, and outcomes for patients with GIC.
METHODS
We performed a secondary analysis of a prospective study that examined 120 consecutive patients who underwent transperitoneal aortic revascularization for aneurysmal or occlusive disease.
RESULTS
The following 29 GICs developed in 25 patients (21%) within 30 days of aortic surgery: paralytic ileus that required replacement of nasogastric tubes (n = 12), upper gastrointestinal bleeding (n = 5), Clostridium difficile enterocolitis (n = 5), acute cholecystitis (n = 2), mechanical obstruction (n = 2), ascites (n = 2), and colon ischemia (n = 1). Seven patients required operations for GICs after aortic revascularization. A comparison of patients with and without GICs showed no differences in the prevalence of risk factors, presence of mesenteric artery stenoses, coexisting medical illnesses, antecedent gastrointestinal history, operative indication, preoperative fluid administration, or duration of operation. However, patients with GICs had more intraoperative complications (P = .004), greater intraoperative blood loss (P = .02), and more fluids during the postoperative period (P = .008). The mean duration of mechanical ventilation was 71 +/- 23 hours for patients with GICs versus 7 +/- 2 hours for patients without GICs (P = .006). A higher prevalence of pulmonary (P = .004) and renal (P = .001) complications was seen in the patients with GICs. The mean stay in the intensive care unit was 16 +/- 2 days for patients with GICs as compared with 5 +/- 0.4 days for patients without GICs (P < .001). Four deaths occurred, all caused by multisystem organ failure: 3 patients had GICs, and 1 did not have a GIC (P = .007).
CONCLUSIONS
These results show that GICs are prevalent in transperitoneal aortic surgery and are associated with severe morbidity rates, increased hospital costs because of prolonged stay, and increased mortality rates. Some GICs appear to be associated with intraoperative events that lead to visceral hypoperfusion, and others can be attributed to mechanical causes. However, none of the variables examined in this study were predictive of GICs. In all, GICs should be considered serious adverse sequela after aortic revascularization. Because no risk factors for GICs have been identified, these complications currently cannot be prevented.
Topics: Acute Disease; Aorta; Aortic Aneurysm, Abdominal; Aortic Diseases; Ascites; Cholecystitis; Clostridioides difficile; Colitis, Ischemic; Enterocolitis; Female; Fluid Therapy; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Hypertension; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Male; Mesenteric Vascular Occlusion; Middle Aged; Postoperative Complications; Prospective Studies; Risk Factors; Smoking; Time Factors; Treatment Outcome
PubMed: 9737449
DOI: 10.1016/s0741-5214(98)70125-9 -
Medicine May 2020Rare cases of euglycemic diabetic ketoacidosis (eu-DKA) have been reported after the administration of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. No reports...
RATIONALE
Rare cases of euglycemic diabetic ketoacidosis (eu-DKA) have been reported after the administration of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. No reports have described eu-DKA complicated by hypernatremia due to SGLT-2 inhibitors.
PATIENT CONCERNS
A 76-year-old woman with a 40-year history of type 2 diabetes mellitus (DM), for which metformin (1000 mg/day) and dapagliflozin (10 mg/day) were prescribed, presented with malaise, fever, and oliguria. On presentation, her white blood cell count (11,800/μL), serum creatinine (3.2 mg/dL), and C-reactive protein (54 mg/L) were abnormal. Bilateral pyeloureteritis and diffuse paralytic ileus were present. She received intravenous antibiotics and total parenteral nutrition, and was asked to fast. Her renal function and ileus briefly improved. Oral hypoglycemic agents, metformin and dapagliflozin, along with enteral feeding were reinstituted on day 3 of hospitalization. However, on day 6 of hospitalization, the patient developed an altered state of consciousness including confusion, lethargy, and stupor. Several laboratory abnormalities suggestive of ketoacidosis with euglycemia were noted.
DIAGNOSES
The patient was diagnosed with eu-DKA accompanied by severe hypernatremia (corrected serum Na concentration, 163 mEq/L) and hypokalemia following dapagliflozin re-administration.
INTERVENTIONS
The patient was treated with indicated intravenous fluid therapy. Dapagliflozin use was discontinued.
OUTCOMES
The patient's mental status and laboratory findings improved gradually, and she was discharged on maintenance doses of insulin and metformin on day 14 of hospitalization.
LESSONS
Acute illnesses such as diffuse paralytic ileus and urinary tract infection, and dietary restrictions or fasting in patients with DM can be considered potential predisposing factors for SGLT-2 inhibitor-associated eu-DKA. For patients with diabetes in the setting of acute morbidity, timely resumption of the SGLT-2 inhibitor therapy should be carefully determined. In addition, eu-DKA due to SGLT-2 inhibitor use may be accompanied by electrolyte disturbances such as hypernatremia and hypokalemia.
Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Fluid Therapy; Glucosides; Humans; Hypernatremia; Hypoglycemic Agents; Hypokalemia; Insulin; Intestinal Pseudo-Obstruction; Kidney Pelvis; Metformin; Patient Discharge; Sodium-Glucose Transporter 2 Inhibitors; Ureter; Withholding Treatment
PubMed: 32481295
DOI: 10.1097/MD.0000000000020228 -
British Medical Journal (Clinical... Aug 1982
Topics: Aged; Female; Humans; Hypoparathyroidism; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Urination Disorders
PubMed: 6809133
DOI: 10.1136/bmj.285.6340.477 -
The Journal of International Medical... Apr 2020Guillain-Barré syndrome (GBS) is an acute neuroimmunological disorder characterized by rapidly ascending symmetrical limb weakness, areflexia, and sensory deficits....
Guillain-Barré syndrome (GBS) is an acute neuroimmunological disorder characterized by rapidly ascending symmetrical limb weakness, areflexia, and sensory deficits. Approximately 65% of patients with GBS present with autonomic dysfunction, which commonly occurs in advanced stages. However, paralytic ileus, a sign of gastrointestinal dysautonomia, is rare as the presenting feature in GBS before motor weakness becomes evident. We report the case of a 54-year-old man admitted to the Emergency Department with paralytic ileus as the prodromal feature in early-stage GBS. Total parenteral feeding and prokinetic use were initiated, but no clinical improvement was observed. The patient showed rapid progression to quadriplegia, which was ultimately determined to be respiratory muscle failure requiring mechanical ventilation and intensive care unit admission. He underwent 5 days of intravenous immunoglobulin therapy and muscle strength was partially improved thereafter. However, the patient's enteral nutritional support was undesirable because of persistent poor gastric emptying complicated by fungemia and profound sepsis throughout the hospital course. Finally, he died 1 month after admission. Ignorance of this unusual prodrome to GBS could result in delayed treatment, along with potential progression to life-threatening events. Early recognition of GBS and prompt immunotherapy are critical for reducing morbidity and mortality.
Topics: Autonomic Nervous System Diseases; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Intestinal Pseudo-Obstruction; Male; Middle Aged; Muscle Weakness
PubMed: 31875750
DOI: 10.1177/0300060519893169 -
Brain : a Journal of Neurology May 2014Balanced pools of deoxyribonucleoside triphosphate precursors are required for DNA replication, and alterations of this balance are relevant to human mitochondrial...
Balanced pools of deoxyribonucleoside triphosphate precursors are required for DNA replication, and alterations of this balance are relevant to human mitochondrial diseases including mitochondrial neurogastrointestinal encephalopathy. In this disease, autosomal recessive TYMP mutations cause severe reductions of thymidine phosphorylase activity; marked elevations of the pyrimidine nucleosides thymidine and deoxyuridine in plasma and tissues, and somatic multiple deletions, depletion and site-specific point mutations of mitochondrial DNA. Thymidine phosphorylase and uridine phosphorylase double knockout mice recapitulated several features of these patients including thymidine phosphorylase activity deficiency, elevated thymidine and deoxyuridine in tissues, mitochondrial DNA depletion, respiratory chain defects and white matter changes. However, in contrast to patients with this disease, mutant mice showed mitochondrial alterations only in the brain. To test the hypothesis that elevated levels of nucleotides cause unbalanced deoxyribonucleoside triphosphate pools and, in turn, pathogenic mitochondrial DNA instability, we have stressed double knockout mice with exogenous thymidine and deoxyuridine, and assessed clinical, neuroradiological, histological, molecular, and biochemical consequences. Mutant mice treated with exogenous thymidine and deoxyuridine showed reduced survival, body weight, and muscle strength, relative to untreated animals. Moreover, in treated mutants, leukoencephalopathy, a hallmark of the disease, was enhanced and the small intestine showed a reduction of smooth muscle cells and increased fibrosis. Levels of mitochondrial DNA were depleted not only in the brain but also in the small intestine, and deoxyribonucleoside triphosphate imbalance was observed in the brain. The relative proportion, rather than the absolute amount of deoxyribonucleoside triphosphate, was critical for mitochondrial DNA maintenance. Thus, our results demonstrate that stress of exogenous pyrimidine nucleosides enhances the mitochondrial phenotype of our knockout mice. Our mouse studies provide insights into the pathogenic role of thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal encephalopathy and an excellent model to study new therapeutic approaches.
Topics: Age Factors; Animals; Body Weight; Brain; Deoxyribonucleosides; Disease Models, Animal; Intestinal Pseudo-Obstruction; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Motor Activity; Muscle Strength; Muscle, Skeletal; Muscular Dystrophy, Oculopharyngeal; Ophthalmoplegia; Psychomotor Disorders; Succinate Dehydrogenase; Thymidine; Thymidine Phosphorylase; Uridine Phosphorylase
PubMed: 24727567
DOI: 10.1093/brain/awu068 -
Journal of Medical Case Reports Oct 2022Mitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine...
BACKGROUND
Mitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. Mitochondrial neurogastrointestinal encephalopathy is a progressive degenerative disease characterized by a distinctive tetrad of gastrointestinal dysmotility, peripheral neuropathy, ophthalmoplegia with ptosis, and asymptomatic leukoencephalopathy. It provides a diagnostic dilemma to physicians in regions like Pakistan because of a lack of genetic study availability and associated financial constraints of the population. However, with careful examination and a few basic investigations, mitochondrial neurogastrointestinal encephalopathy can be diagnosed by ruling out most of the close differentials.
CASE PRESENTATION
We report the case of a 23-year-old Asian female whose chief complaints were epigastric pain, bilious emesis, weight loss for 3 months, and bilateral lower limb weakness for 20 days. All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. Because of financial constraints, genetic studies could not be performed. The patient was managed with a multidisciplinary approach involving gastroenterology, physiotherapy, and nutrition departments. Currently, therapeutic options for the disease include allogeneic hematopoietic stem cell transplant and carrier erythrocyte entrapped thymidine phosphorylase; however, these could not be provided to the patient owing to certain limitations.
CONCLUSIONS
As misdiagnosis and delayed diagnosis are quite common in this disease, the prime objective of this case report is to increase the basic understanding of this disease, especially its signs and symptoms, and address the limitations regarding the diagnostic investigations and management of patients with mitochondrial neurogastrointestinal encephalopathy.
Topics: Adult; Female; Humans; Intestinal Pseudo-Obstruction; Mitochondrial Encephalomyopathies; Muscular Dystrophy, Oculopharyngeal; Ophthalmoplegia; Pakistan; Thymidine Phosphorylase; Young Adult
PubMed: 36192783
DOI: 10.1186/s13256-022-03582-6 -
Trials Feb 2023Acute pancreatitis is a serious threat to human health and gastrointestinal dysmotility is a common complication for acute pancreatitis patients, resulting in delayed...
BACKGROUND
Acute pancreatitis is a serious threat to human health and gastrointestinal dysmotility is a common complication for acute pancreatitis patients, resulting in delayed feeding, oral feeding intolerance, paralytic ileus, and abdominal compartment syndrome. Currently, there are limited treatment for this complication. Neostigmine is known to increase gastrointestinal motility and has been used to treat gastrointestinal dysmotility after surgery. However, research in treating acute pancreatitis with neostigmine is currently limited.
METHODS
This trial is a randomized, placebo-controlled, double-blinded, mono-centric trial that will test the hypothesis that neostigmine can improve gastrointestinal motility in patients with severe acute pancreatitis. Up to 56 patients will be randomized in this study receiving 0.5 mg/1 ml of neostigmine methylsulfate injection twice per day or 1 ml of saline injection twice per day. Defection time (aim 1), mortality and organ failure (aim 2), borborygmus, starting of enteral nutrition and intra-abdominal pressure (aim 3), and length of ICU and hospital stay (aim 4) will be assessed.
DISCUSSION
Findings from this study will provide data supporting the usage of neostigmine for treating severe acute pancreatitis patients with gastrointestinal dysmotility.
TRIAL REGISTRATION
This study is registered on chictr.org.cn with the identifier as ChiCTR2200058305. Registered on April 5, 2022.
Topics: Humans; Infant, Newborn; Neostigmine; Pancreatitis; Acute Disease; Enteral Nutrition; Intestinal Pseudo-Obstruction; Randomized Controlled Trials as Topic
PubMed: 36747275
DOI: 10.1186/s13063-023-07086-6 -
Laboratory Investigation; a Journal of... Jul 2007The enteric glial cells, in addition to being support structures for the enteric nervous system, have many other additional roles, such as modulators for the homeostasis... (Review)
Review
The enteric glial cells, in addition to being support structures for the enteric nervous system, have many other additional roles, such as modulators for the homeostasis of enteric neurons, cells involved in enteric neurotransmission and antigen-presenting cells. Moreover, in the last years, data have been accumulating that demonstrate a possible active role of these cells in the pathophysiology of gastrointestinal motor activity. Thus, as also shown by recent evidence in both experimental animal models, and in some human diseases, alterations of enteric glial cells might have some role in the development of intestinal motor abnormalities.
Topics: Animals; Disease Models, Animal; Enteric Nervous System; Enteritis; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Immune System; Immunohistochemistry; Intestinal Pseudo-Obstruction; Intestines; Mice; Neuroglia
PubMed: 17483847
DOI: 10.1038/labinvest.3700564 -
Scientific Reports Aug 2021Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have...
Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remain unclear. Therefore, we aimed to examine ENSC integration using an adapted ex vivo organotypic culture system. Donor ENSC were obtained from Wnt1;R26R mice allowing specific labelling, selection and fate-mapping of cells. YFP neurospheres were transplanted to C57BL6/J (6-8-week-old) colonic tissue and maintained in organotypic culture for up to 21 days. We analysed and quantified donor cell integration within recipient tissues at 7, 14 and 21 days, along with assessing the structural and molecular consequences of ENSC integration. We found that organotypically cultured tissues were well preserved up to 21-days in ex vivo culture, which allowed for assessment of donor cell integration after transplantation. Donor ENSC-derived cells integrated across the colonic wall in a dynamic fashion, across a three-week period. Following transplantation, donor cells displayed two integrative patterns; longitudinal migration and medial invasion which allowed donor cells to populate colonic tissue. Moreover, significant remodelling of the intestinal ECM and musculature occurred upon transplantation, to facilitate donor cell integration within endogenous enteric ganglia. These results provide critical evidence on the timescale and mechanisms, which regulate donor ENSC integration, within recipient gut tissue, which are important considerations in the future clinical translation of stem cell therapies for enteric disease.
Topics: Animals; Cell Culture Techniques; Colon; Enteric Nervous System; Female; Intestinal Pseudo-Obstruction; Intestine, Small; Male; Mice; Mice, Inbred C57BL; Neural Crest; Neural Stem Cells; Neurons; Organoids; Stem Cell Transplantation
PubMed: 34354183
DOI: 10.1038/s41598-021-95434-4