-
The International Journal of... Jun 2024Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many...
BACKGROUND
Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed mice.
METHODS
Adult male mice were exposed to HS (33 oC 2h daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble thrombomodulin (TM, 1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide, high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were measured biochemically. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined.
RESULTS
Compared to controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice.
CONCLUSIONS
The findings suggest that heat stress can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. Thrombomodulin, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.
PubMed: 38938182
DOI: 10.1093/ijnp/pyae027 -
Journal of Agricultural and Food... Jun 2024Hemoglobin is an excellent source of iron supplements, and its hydrolyzate spontaneously binds iron during digestion and promotes iron absorption in vivo. However, the...
Hemoglobin is an excellent source of iron supplements, and its hydrolyzate spontaneously binds iron during digestion and promotes iron absorption in vivo. However, the underlying mechanisms of what peptides bind and how they bind iron ions remain unclear. This study prepared the porcine hemoglobin hydrolyzate through enzymatic hydrolysis and acid treatment and investigated the mechanisms of hemoglobin hydrolyzate on iron absorption through the determination of iron levels in dietary intervention mice, iron binding site analyses, peptide digestion analyses, molecular simulation docking, and INT407 cell validation. The results showed that ingestion of the hemoglobin hydrolyzate diets increased iron levels in the blood of mice, accompanied by the upregulation of duodenal iron circulation-related genes such as ferritin, PCBP1, and HP. Carboxyl, imidazole groups, and aromatic amino acid residues were iron binding sites of hemoglobin hydrolyzate during digestion. VDEVGGEA and VDEVGGE were found to involve the spontaneous and efficient binding of hemoglobin hydrolyzate to iron ions in the intestinal cavity. In particular, the DEVGGE peptide was the typical sequence for hemoglobin hydrolytic peptides to exert iron binding activity.
PubMed: 38935870
DOI: 10.1021/acs.jafc.4c00364 -
Gut Microbes 2024The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the...
The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2α. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced α-diversity of microbiota, and led to becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of .
Topics: Animals; Mice; Gastrointestinal Microbiome; Iron, Dietary; Cation Transport Proteins; Liver; Duodenum; Hepcidins; Ferritins; Germ-Free Life; Host Microbial Interactions; Lung; Iron; Basic Helix-Loop-Helix Transcription Factors; Bacteria; Mice, Inbred C57BL; Hemoglobins; Male
PubMed: 38935764
DOI: 10.1080/19490976.2024.2361660 -
Journal of Inflammation Research 2024Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In...
AIM
Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In fact, when the pseudoaneurysm is small in diameter, diagnosis can be particularly challenging. Timely and effective diagnosis and treatment is therefore of great significance, and in this case, endoscopy, combined with intravascular therapy, can provide an effective approach, especially since it removes the need for surgery while yielding favorable outcomes.
CASE SUMMARY
A 75-year-old old man presented to the hospital's emergency department with hematemesis and black stool. Despite conservative treatments such as "acid suppression, fluid resupply, hemostasis and blood transfusion", no significant improvement was noted. Emergency gastroscopy subsequently revealed an ulcer in the duodenal bulb (Figure 1), with an exposed thrombotic head and active bleeding on the surface. In addition, abdominal computed tomography (Figure 2) showed no obvious HAPA manifestations. After unsuccessful endoscopic hemostasis, angiography was performed (Figure 3) and a pseudotumor-like dilatation measuring 5.56 mm in diameter was found at the distal end of the proximal branch vessel of the common hepatic artery. Following spring coil embolization (Figure 4), the patient's condition improved and he was discharged from the hospital, with a follow-up after six months showing no signs of recurrence or complications.
CONCLUSION
Duodenal ulcer hemorrhages due to small hepatic pseudoaneurysms are very rare, with endoscopic intervention being effective for such cases.
PubMed: 38933359
DOI: 10.2147/JIR.S467969 -
Frontiers in Immunology 2024Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve...
Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve intestinal mucosal inflammatory infiltrates, but histopathological evaluation of intestinal biopsies from dogs with CIE fails to guide treatment, inform prognosis, or correlate with clinical remission. We employed single-cell RNA sequencing to catalog and compare the diversity of cells present in duodenal mucosal endoscopic biopsies from 3 healthy dogs and 4 dogs with CIE. Through characterization of 35,668 cells, we identified 31 transcriptomically distinct cell populations, including T cells, epithelial cells, and myeloid cells. Both healthy and CIE samples contributed to each cell population. T cells were broadly subdivided into GZMA (putatively annotated as tissue resident) and IL7R (putatively annotated as non-resident) T cell categories, with evidence of a skewed proportion favoring an increase in the relative proportion of IL7R T cells in CIE dogs. Among the myeloid cells, neutrophils from CIE samples exhibited inflammatory (SOD2 and IL1A) gene expression signatures. Numerous differentially expressed genes were identified in epithelial cells, with gene set enrichment analysis suggesting enterocytes from CIE dogs may be undergoing stress responses and have altered metabolic properties. Overall, this work reveals the previously unappreciated cellular heterogeneity in canine duodenal mucosa and provides new insights into molecular mechanisms which may contribute to intestinal dysfunction in CIE. The cell type gene signatures developed through this study may also be used to better understand the subtleties of canine intestinal physiology in health and disease.
Topics: Animals; Dogs; Duodenum; Single-Cell Analysis; Dog Diseases; Transcriptome; Gene Expression Profiling; Intestinal Mucosa; Chronic Disease; Male; Female; T-Lymphocytes
PubMed: 38933260
DOI: 10.3389/fimmu.2024.1397590 -
The American Journal of Case Reports Jun 2024BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is...
BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is obstruction caused by a neoplastic mass. Nevertheless, in exceptionally rare cases, these symptoms arise from complications linked to a visceral artery aneurysm. CASE REPORT We present a case of a 60-year-old man with immunodeficiency and Sneddon-Wilkinson disease (a rare subcorneal pustular dermatosis), who developed a pancreaticoduodenal aneurysm of uncertain origin, associated with pancreatic mass, retroperitoneal hematoma, and duodenal obstruction. The treatment approach included transcatheter arterial coil embolization with supportive measures such as parenteral nutrition, a nasogastric tube, octreotide administration, and antiemetics. Despite these interventions, persistence gastrointestinal symptoms prompted an endoscopic ultrasound fine-needle aspiration to rule out malignancy. The biopsy confirmed localized fibro-inflammation. Although he was initially considered for a gastro-jejunal bypass, conservative management effectively improved the pancreatic lesion and duodenal obstruction, leading to discontinuation of parenteral nutrition. The patient was able to resume a regular diet 4 weeks after embolization. CONCLUSIONS Pancreaticoduodenal artery aneurysm is a rare visceral aneurysm with multiple etiologies and potentially fatal consequences. We report an unusual case of a pancreaticoduodenal artery aneurysm associated with pancreatic mass and duodenal obstruction. This diagnosis warrants consideration when an immunodeficient patient presents symptoms of abdominal pain and vomiting. Early endovascular embolization, combined with conservative approaches, effectively alleviated the symptoms in our patient.
Topics: Humans; Male; Middle Aged; Aneurysm, False; Pancreas; Duodenal Obstruction; Duodenum; Embolization, Therapeutic
PubMed: 38932438
DOI: 10.12659/AJCR.943879 -
Nutrients Jun 2024The hawthorn fruit is an interesting medicinal plant that has several biological features, especially related to anti-inflammatory, antioxidant and immune-modulating...
The hawthorn fruit is an interesting medicinal plant that has several biological features, especially related to anti-inflammatory, antioxidant and immune-modulating actions, and boosting general health. In this study, we aimed to clarify the immunological effects of hawthorn vinegar on immunity and general health. We also focused on three different production processes to improve the antioxidant activity of hawthorn vinegar (2) Methods: In the study, besides the traditional production of hawthorn vinegar (N), thermal pasteurization (P) and ultrasound (U) techniques were applied to vinegars. A total of 56 female adult Wistar albino rats were randomly allocated into seven groups; Control, N0.5 (regular vinegar; 0.5 mL/kgbw), N1 (regular vinegar; 1 mL/kgbw), P0.5 (pasteurized vinegar; 0.5 mL/kgbw), P1 (pasteurized vinegar; 1 mL/kgbw), U0.5 (ultrasound treated vinegar; 0.5 mL/kgbw), and U1 (ultrasound treated vinegar; 1 mL/kgbw). Vinegars were administered by oral gavage daily. The average weight gains, body mass index, and blood hematological parameters were measured, and the Neutrophil Lymphocyte ratio was calculated. The plasma IL-1β and TNF-α values, and MDA, IL-1β and TNF-α values of intestinal tissue, were determined. Also, the streptavidin-biotin-peroxidase complex method was applied to determine the expressions of TNF-α and IL-1β in duodenum. (3) Results: There was a decreasing tendency in the average weight gains in all vinegar groups compared to the control group. In addition, there was an increase in NL ratio in all vinegar groups, although not significant. There were no statistical differences among all vinegar groups, although decreases were observed in plasma IL-1β. Also, the plasma TNF-α values showed slight increases in high-dose-of-vinegar groups (N1, P1 and U1), although not significant. In addition, the intestinal tissue IL-1β value tended to increase in groups N0.5, N1 and P0.5, while it tended to decrease in P1, U0.5 and U1. On the other hand, there were slight increases in the TNF-α values of intestinal tissue in all groups compared to control, although these were not significant. Furthermore, the intensive expressions of TNF-α and IL-1β were determined in groups U0.5 and U1. (4) Conclusions: The results suggest that either high doses or ultrasound applications of hawthorn vinegar have positive effects on intestinal health, boosting immunity and general health.
Topics: Animals; Female; Acetic Acid; Rats, Wistar; Crataegus; Rats; Antioxidants; Interleukin-1beta; Tumor Necrosis Factor-alpha; Fruit
PubMed: 38931223
DOI: 10.3390/nu16121868 -
Journal of Medical Case Reports Jun 2024Due to rarity of duodenal GISTs, clinicians have few information about its clinical features, diagnosis, management and prognosis. (Review)
Review
BACKGROUND
Due to rarity of duodenal GISTs, clinicians have few information about its clinical features, diagnosis, management and prognosis.
CASE REPORT
We report a case of promptly diagnosed duodenal GIST in a 61-year-old Egyptian man presented shocked with severe attack of hematemesis and melena. Upper gastroduodenal endoscopy was done and revealed a large ulcerating bleeding mass at first part of duodenum 4 hemo-clips were applied with good hemostasis. An exploratory laparotomy and distal gastrectomy, duodenectomy and gastrojejunostomy were performed. The morphology of the mass combined with immunohistochemistry was consistent with duodenal gastrointestinal stromal tumours (GISTs) of high risk type. The patient is on amatinib one tablet daily and he was well with no evidence of tumor recurrence.
CONCLUSION
despite being rare, emergency presentation with sudden severe, life-threatening hemorrhagic shock duodenal GISTs might be a cause of potentially lethal massive combined upper and lower gastrointestinal bleeding which is the key feature of this rare and challenging tumor.
Topics: Humans; Gastrointestinal Stromal Tumors; Male; Middle Aged; Gastrointestinal Hemorrhage; Duodenal Neoplasms; Shock, Hemorrhagic; Melena; Hematemesis; Gastrectomy
PubMed: 38907357
DOI: 10.1186/s13256-024-04597-x -
Surgical Endoscopy Jun 2024Sleeve gastrectomy (SG) increased in popularity after 2010 but recent data suggest it has concerning rates of gastroesophageal reflux and need for conversions. This...
BACKGROUND
Sleeve gastrectomy (SG) increased in popularity after 2010 but recent data suggest it has concerning rates of gastroesophageal reflux and need for conversions. This study aims to evaluate recent trends in the utilization of bariatric procedures, associated complications, and conversions using an administrative claims database in the United States.
METHODS
We included adults who had bariatric procedures from 2000 to 2020 with continuous enrollment for at least 6 months in the MarketScan Commercial Claims and Encounters database. Index bariatric procedures and subsequent revisions or conversions were identified using CPT codes. Baseline comorbidities and postoperative complications were identified with ICD-9-CM and ICD-10 codes. Cumulative incidences of complications were estimated at 30-days, 6-months, and 1-year and compared with stabilized inverse probability of treatment weighted Kaplan-Meier analysis.
RESULTS
We identified 349,411 bariatric procedures and 5521 conversions or revisions. The sampled SG volume appeared to begin declining in 2018 while Roux-en-Y gastric bypass (RYGB) remained steady. Compared to RYGB, SG was associated with lower 1-year incidence [aHR, (95% CIs)] for 30-days readmission [0.65, (0.64-0.68)], dehydration [0.75, (0.73-0.78)], nausea or vomiting [0.70, (0.69-0.72)], dysphagia [0.55, (0.53-0.57)], and gastrointestinal hemorrhage [0.43, (0.40-0.46)]. Compared to RYGB, SG was associated with higher 1-year incidence [aHR, (95% CIs)] of esophagogastroduodenoscopy [1.13, (1.11-1.15)], heartburn [1.38, (1.28-1.49)], gastritis [4.28, (4.14-4.44)], portal vein thrombosis [3.93, (2.82-5.48)], and hernias of all types [1.36, (1.34-1.39)]. There were more conversions from SG to RYGB than re-sleeving procedures. SG had a significantly lower 1-year incidence of other non-revisional surgical interventions when compared to RYGB.
CONCLUSIONS
The overall volume of bariatric procedures within the claims database appeared to be declining over the last 10 years. The decreasing proportion of SG and the increasing proportion of RYGB suggest the specific complications of SG may be driving this trend. Clearly, RYGB should remain an important tool in the bariatric surgeon's armamentarium.
PubMed: 38902405
DOI: 10.1007/s00464-024-10985-7 -
Clinical Oncology (Royal College of... May 2024Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the...
AIMS
Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC.
MATERIALS AND METHODS
This was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0-3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated.
RESULTS
55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5-37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0-1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3-18.7). Median OS post diagnosis was 19 months (95% CI 15.9-22.1). One-year local control post SMART was 65%.
CONCLUSION
This is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes.
PubMed: 38902119
DOI: 10.1016/j.clon.2024.05.012