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Cureus Mar 2024Due to the advances in endoscopic technology, surgery for duodenal ulcer (DU) bleeding has decreased, although surgery is still necessary for more complicated cases. The...
Due to the advances in endoscopic technology, surgery for duodenal ulcer (DU) bleeding has decreased, although surgery is still necessary for more complicated cases. The concept of damage control surgery (DCS) has been established in the field of trauma, and a simple surgical approach may be preferable in serious cases such as uncontrolled DU bleeding. We present a successful case of bleeding with massive hematoma and perforation of the duodenum due to an over-the-scope clip that was treated by a less invasive surgical approach with consideration of the DCS.
PubMed: 38633969
DOI: 10.7759/cureus.56359 -
Redox Biology Jun 2024Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload...
Differentiation of intestinal stem cells toward goblet cells under systemic iron overload stress are associated with inhibition of Notch signaling pathway and ferroptosis.
Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload influences intestinal mucosa remains unknown. Here, the aim of current study was to investigate the effects of iron overload on the proliferation and differentiation of intestinal stem cells (ISCs). An iron overload mouse model was established by intraperitoneal injection of 120 mg/kg body weight iron dextran once a fortnight for a duration of 12 weeks, and an iron overload enteroid model was produced by treatment with 3 mM or 10 mM of ferric ammonium citrate for 24 h. We found that iron overload caused damage to intestinal morphology with a 64 % reduction in villus height/crypt depth ratio, and microvilli injury in the duodenum. Iron overload mediated epithelial function by inhibiting the expression of nutrient transporters and enhancing the expression of secretory factors in the duodenum. Meanwhile, iron overload inhibited the proliferation of ISCs and regulated their differentiation into secretory mature cells, such as goblet cells, through inhibiting Notch signaling pathway both in mice and enteroid. Furthermore, iron overload caused oxidative stress and ferroptosis in intestinal epithelial cells. In addition, ferroptosis could also inhibit Notch signaling pathway, and affected the proliferation and differentiation of ISCs. These findings reveal the regulatory role of iron overload on the proliferation and differentiation of ISCs, providing a new insight into the internal mechanism of iron overload affecting intestinal health, and offering important theoretical basis for the scientific application of iron nutrition regulation.
Topics: Animals; Ferroptosis; Mice; Goblet Cells; Iron Overload; Signal Transduction; Stem Cells; Cell Differentiation; Receptors, Notch; Oxidative Stress; Intestinal Mucosa; Cell Proliferation; Disease Models, Animal; Male
PubMed: 38631120
DOI: 10.1016/j.redox.2024.103160 -
Trials Apr 2024Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other...
BACKGROUND
Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD).
METHODS/DESIGN
The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival.
DISCUSSION
The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care.
ETHICS AND DISSEMINATION
The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation.
TRIAL REGISTRATION
EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.
Topics: Adult; Humans; Adrenergic beta-Antagonists; Ascites; Carvedilol; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hypertension, Portal; Liver Cirrhosis; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic
PubMed: 38627804
DOI: 10.1186/s13063-024-08063-3 -
PloS One 2024Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors...
Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.
Topics: Female; Pregnancy; Mice; Humans; Animals; Diabetes, Gestational; Streptozocin; Mice, Inbred C57BL; Insulin; Diabetes Mellitus, Experimental; Obesity; Glucose; Phenotype; Citrates; Blood Glucose
PubMed: 38626157
DOI: 10.1371/journal.pone.0302041 -
Journal of Animal Science and Technology Nov 2023Selenium (Se) is an essential trace mineral that plays an important role in physiological processes by regulating the antioxidant defense system and enhancing immunity....
Selenium (Se) is an essential trace mineral that plays an important role in physiological processes by regulating the antioxidant defense system and enhancing immunity. Chromium is an essential mineral involved in carbohydrate and lipid metabolism and also plays a role in maintaining normal insulin function. Based on these advantages, we hypothesized that the addition of selenomethionine (SeMet) and organic chromium (OC) to broiler diets would increase Se deposition, antioxidant capacity and immune response in meat. Therefore, this study analyzed the effects of OC and SeMet on growh performance, nutrients digestibility, blood profiles, intestinal morphology, meat quality characteristics, and taxonomic analysis of broilers. A total of 168 one-day-old broiler chicken (Arbor Acres) were randomly allotted to 3 groups based on the initial body weight of 37.33 ± 0.24 g with 7 replicate per 8 birds (mixed sex). The experiments period was 28 days. Dietary treatments were folloewd: Basal diets based on corn-soybean meal (CON), basal diet supplemented with 0.2 ppm OC and 0.2 ppm SeMet (CS4), and basal diet supplemented with 0.4 ppm OC and 0.4 ppm SeMet (CS8). Supplementation of OC and SeMet did not affect on growth performance, nutrient digestibility. However, CS8 supplementation increased in duodenum villus height and villus height : crypt depth, and increased in breast meat Se deposition. In addition, CS8 group showed higher uric acid and total antioxidant status than CON group. Taxonomic analysis at phylum level revealed that and of CS4 and CS8 were lower than CON group. In genus level, the relative abundance of fecal and of CS4 and CS8 groups were higher than CON group. In short, 0.4 ppm OC and 0.4 ppm SeMet supplementation to broiler diet supporitng positive gut microbiome change, also enhancing antioxidant capacity, and Se deposition in breast meat.
PubMed: 38616877
DOI: 10.5187/jast.2023.e32 -
Medicine Apr 2024Laparoscopic pancreaticoduodenectomy (LPD) is an alternative to open pancreaticoduodenectomy (OPD) for treatment of periampullary cancer in selected patients. However,...
Laparoscopic pancreaticoduodenectomy (LPD) is an alternative to open pancreaticoduodenectomy (OPD) for treatment of periampullary cancer in selected patients. However, this is a difficult procedure with a high complication rate. We conducted a prospective cohort study of 85 patients with suspected periampullary cancer who underwent LPD from February 2017 to January 2022 at University Medical Center at Ho Chi Minh City, Vietnam. Among these, 15 patients were excluded from the data analysis because of benign disease confirmed by postoperative pathological examination. Among 70 patients, the mean age was 58.9 ± 8.9 years old and 51.4% were female. The conversion rate to open surgery was 7.1% (n = 5). Among those underwent LPD, the mean operating time and estimated blood loss were 509 ± 94 minutes and 267 ± 102 mL, respectively. The median length of hospital stay was 8 days, interquartile range (IQR) 7-12 days. The percentage of cumulative morbidity, pancreatic fistula and major complication was 35.4%, 12.3%, and 13.8%, respectively. The median of comprehensive complication index (CCI) was 26.2 (IQR 20.9-29.6). Three patients required reoperation due to severe pancreatic fistula (n = 2) and necrotizing pancreatitis (n = 1). There was no death after ninety-day. The average number of harvested lymph nodes was 16.6 ± 5.1. The percentage of R0 resection was 100%. With properly selected patients, LPD can be a feasible, safe and effective approach with acceptable short-term outcomes.
Topics: Humans; Female; Middle Aged; Aged; Male; Pancreaticoduodenectomy; Vietnam; Feasibility Studies; Pancreatic Fistula; Prospective Studies; Duodenal Neoplasms; Laparoscopy
PubMed: 38608081
DOI: 10.1097/MD.0000000000037769 -
Journal of Animal Science and... Apr 2024Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens. A total of 1,365 one-day-old male Ross 308 broiler chickens were...
BACKGROUND
Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens. A total of 1,365 one-day-old male Ross 308 broiler chickens were randomly divided into 5 treatments groups with 21 replicates, 13 birds per replicate. The present research investigated effects of microbial muramidase or a precision glycan alone or in combination on growth performance, apparent total tract digestibility, total blood carotenoid content, intestinal villus length, meat quality and gut microbiota in broiler chickens. Treatments included: NC: negative control (basal diet group); PC: positive control (basal diet + 0.02% probiotics); MR: basal diet + 0.035% microbial muramidase; PG: basal diet + 0.1% precision glycan; and MRPG: basal diet + 0.025% MR + 0.1% PG, respectively.
RESULTS
MRPG group increased the body weight gain and feed intake (P < 0.05) compared with NC group. Moreover, it significantly increased total serum carotenoid (P < 0.05) and MRPG altered the microbial diversity in ileum contents. The MRPG treatment group increased the abundance of the phylum Firmicutes, and family Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Lactobacillaceae, Peptostreptococcaceae and decreased the abundance of the phylum Campilobacterota, Bacteroidota and family Bacteroidaceae. Compared with the NC group, the chickens fed MRPG showed significantly increased in duodenum villus length at end the trial.
CONCLUSION
In this study, overall results showed that the synergetic effects of MR and PG showed enhancing growth performance, total serum carotenoid level and altering gut microbiota composition of broilers. The current research indicates that co-supplementation of MR and PG in broiler diets enhances intestinal health, consequently leading to an increased broiler production.
PubMed: 38594781
DOI: 10.1186/s40104-024-01010-x -
Blood Advances Jun 2024Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to...
Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.
Topics: Animals; Mice; GPI-Linked Proteins; Hepcidins; Hemochromatosis Protein; Bone Morphogenetic Protein Receptors, Type I; Liver; Iron; Iron Overload; Activin Receptors, Type I; Activin Receptors, Type II
PubMed: 38588481
DOI: 10.1182/bloodadvances.2023012322 -
The American Journal of Gastroenterology Jun 2024Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects...
INTRODUCTION
Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity.
METHODS
Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed.
RESULTS
Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias.
DISCUSSION
Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.
Topics: Humans; Obesity; Female; Male; Overweight; Middle Aged; Gastrointestinal Microbiome; Adult; Duodenum; RNA, Ribosomal, 16S; Biomarkers; Lactobacillus; Bifidobacterium; Aged
PubMed: 38578969
DOI: 10.14309/ajg.0000000000002790 -
World Journal of Clinical Cases Mar 2024Mycobacterium tuberculosis (TB) is the causative agent of TB, a chronic granulomatous illness. This disease is prevalent in low-income countries, posing a significant...
BACKGROUND
Mycobacterium tuberculosis (TB) is the causative agent of TB, a chronic granulomatous illness. This disease is prevalent in low-income countries, posing a significant global health challenge. Gastrointestinal TB is one of the three forms. The disease can mimic other intra-abdominal conditions, leading to delayed diagnosis owing to the absence of specific symptoms. While gastric outlet obstruction (GOO) remains a frequent complication, its incidence has declined with the advent of proton pump inhibitors and eradication therapy. Gastroduodenal TB can cause upper gastrointestinal hemorrhage, obstruction, and malignancy-like tumors.
CASE SUMMARY
A 23-year-old male presented with recurrent epigastric pain, distension, nausea, vomiting, and weight loss, prompting a referral to a gastroenterologist clinic. Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation. However, treatment was interrupted, possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes. Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall. Resection revealed gastric wall effacement with TB.
CONCLUSION
Primary gastric TB is rare, frequently leading to GOO. Given its rarity, suspicions should be promptly raised when encountering relevant symptoms, often requiring surgical intervention for diagnosis and treatment.
PubMed: 38576818
DOI: 10.12998/wjcc.v12.i8.1536