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Frontiers in Pharmacology 2022This study aimed to establish a pharmacological basis for evaluating the effects of bergapten (5-methoxypsoralen) in gastrointestinal diseases and assessment of its...
Pharmacological basis of bergapten in gastrointestinal diseases focusing on H/K ATPase and voltage-gated calcium channel inhibition: A toxicological evaluation on vital organs.
This study aimed to establish a pharmacological basis for evaluating the effects of bergapten (5-methoxypsoralen) in gastrointestinal diseases and assessment of its toxicological profile. The pharmacokinetic profile was evaluated using the SwissADME tool. AUTODOCK and PyRx were used for evaluating the binding affinities. The obtained results were further investigated for a post-dock analysis using Discovery Studio Visualizer 2016. The Desmond software package was used to conduct molecular dynamic simulations of best bound poses. Bergapten was further investigated for antidiarrheal, anti-secretory, charcoal meal transit time, anti-ulcer, anti- activity. Bergapten at a dose of 50, 100, and 200 mg/kg was proved effective in reducing diarrheal secretions, intestinal secretions, and distance moved by charcoal meal. Bergapten at the aforementioned doses acts as a gastroprotective agent in the ethanol-induced ulcer model that can be attributed to its effectiveness against Bergapten shows concentration-dependent relaxation of both spontaneous and K (80 mM)-induced contractions in the isolated rabbit jejunum model; the Ca concentration-response curves (CRCs) were shifted to the right showing potentiating effect similar to papaverine. For molecular investigation, the H/K ATPase inhibitory assay indicated inhibition of the pump comparable to omeprazole. Oxidative stress markers GST, GSH, and catalase showed increased expression, whereas the expression of LPO (lipid peroxidation) was reduced. Histopathological examination indicated marked improvement in cellular morphology. ELISA and western blot confirmed the reduction in inflammatory mediator expression. RT-PCR reduced the mRNA expression level of H/K ATPase, confirming inhibition of the pump. The toxicological profile of bergapten was evaluated by an acute toxicity assay and evaluated for behavioral analysis, and the vital organs were used to analyze biochemical, hematological, and histopathological examination. Bergapten at the tested doses proved to be an antioxidant, anti-inflammatory, anti-ulcer, and antidiarrheal agent and relatively safe in acute toxicity assay.
PubMed: 36467058
DOI: 10.3389/fphar.2022.1005154 -
Cureus Aug 2022Cocaine use is rising in persons ≥50 years old and in black and socioeconomically disadvantaged communities. Cocaine-induced bowel ischemia and gastrointestinal injury...
Cocaine use is rising in persons ≥50 years old and in black and socioeconomically disadvantaged communities. Cocaine-induced bowel ischemia and gastrointestinal injury are deadly findings that have been previously described in the literature. In this report, we present a case of small bowel ischemia, perforation, and upper gastrointestinal hemorrhage co-occurring in a 62-year-old incarcerated male with a 15-year history of cocaine use. The patient presented from jail, peritonitic in septic shock, and was promptly taken for emergent surgical exploration. He was found to have massive fecal peritonitis secondary to full-thickness ischemia and perforation of the jejunum and ileum. Immediately postoperatively, the patient developed a large volume of hemorrhage from multiple gastric and duodenal ulcers refractory to endoscopic intervention, ultimately requiring emergent embolization of the gastroduodenal artery. His course was further complicated by severe septic shock with a blunted response to catecholamine vasopressors. Early recognition and aggressive treatment of the gastrointestinal complications and the unique critical care challenges associated with cocaine use facilitated this patient's eventual full recovery.
PubMed: 36185891
DOI: 10.7759/cureus.28538 -
World Journal of Clinical Cases Sep 2022A post-bulbar duodenal ulcer (PBDU) is an ulcer in the duodenum that is distal to the duodenal bulb. PBDU may coexist with a synchronous posterior ulcer in rare...
BACKGROUND
A post-bulbar duodenal ulcer (PBDU) is an ulcer in the duodenum that is distal to the duodenal bulb. PBDU may coexist with a synchronous posterior ulcer in rare occurrences, resulting in a kissing ulcer (KU). Duodenocaval fistula (DCF) is another uncommon but potentially fatal complication related to PBDU. There is limited knowledge of the scenarios in which PBDU is complicated by KU and DCF simultaneously.
CASE SUMMARY
A 22-year-old man was admitted to the emergency department with abdominal pain, stiffness, and vomiting. The X-ray showed pneumoperitoneum, suggesting a perforated viscus. Laparotomy revealed a KU with anterior perforation and a DCF. After Kocherization, venorrahphy was used to control caval bleeding. Due to the critical condition of the patient, only primary duodenorrahphy with gastrojejunostomy was performed as a damage control strategy. However, later, the patient developed obstructive jaundice and leakage, and two additional jejunal perforations were detected. Due to the poor condition of the duodenum and the involvement of the ampulla in the posterior ulcer, neither primary repair nor pancreatic-free duodenectomy and ampulloplasty/ampullary reimplantation were considered viable; therefore, an emergency pancreaticoduodenectomy was performed, along with resection and anastomosis of the two jejunal perforations. The patient had a smooth recovery after surgery and was discharged after 27 d.
CONCLUSION
The timely diagnosis of PBDU and radical surgery can aid in the smooth recovery of patients, even in the most complex cases.
PubMed: 36157647
DOI: 10.12998/wjcc.v10.i25.9071 -
Molecules (Basel, Switzerland) Sep 2022This present study aimed to delineate D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal,...
Pharmacological Basis of D. Don in Gastrointestinal Diseases with Focusing Effects on H/K-ATPase, Calcium Channels Inhibition and PDE Mediated Signaling: Toxicological Evaluation on Vital Organs.
This present study aimed to delineate D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti , antiulcer effects, and toxicology. The preliminary phytochemical analysis of showed different phytoconstituents and shows different peaks in GC-MC chromatogram. crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50-300 mg/kg) protection (0-100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K-induced contractions and shifted the Ca concentration-response curves (CRCs) to the right, Rh.Cr (0.3-1 mg/mL) and Rh.ETAC (0.1-0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti- effect, also shows an inhibitory effect against H/K-ATPase. showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H/K-ATPase mRNA levels. was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H/K-ATPase pump and voltage-gated L-type calcium channel showed E-values of -8.7 and -9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.
Topics: Animals; Mice; Rabbits; Rats; Adenosine Triphosphatases; Antidiarrheals; Antioxidants; Calcium Channels, L-Type; Castor Oil; Charcoal; Cyclooxygenase 2; Gastrointestinal Diseases; Isoproterenol; Jejunum; NF-kappa B; Parasympatholytics; Phytochemicals; Plant Extracts; RNA, Messenger; Rumex; Rutin; Tumor Necrosis Factors; Verapamil
PubMed: 36144661
DOI: 10.3390/molecules27185919 -
Cureus Aug 2022Postoperative hypoxia is a challenge for surgeons. With the advent of better anesthesia and minimal access surgical techniques, the incidence of postoperative hypoxia in...
Postoperative hypoxia is a challenge for surgeons. With the advent of better anesthesia and minimal access surgical techniques, the incidence of postoperative hypoxia in elective cases has decreased. However, the incidence in life-saving emergency procedures still poses a possible threat, and cases seem under-reported. We report a series of five cases of postoperative hypoxia after laparotomy. These cases comprise mesenteric laceration, proximal jejunal perforation, perforated duodenal ulcer, abdominal tuberculosis, and fall from height. Despite different etiologies, they landed up with the complication of postoperative hypoxia, which was attributable to the type of procedure they underwent and not the indication of the procedure itself. Thus, they form an interesting collection of post-laparotomy hypoxia cases. We present them with a compilation of probable causes of postoperative hypoxia in such cases. Postoperative hypoxia presents a diagnostic challenge and requires timely suspicion, prompt intervention to eliminate the cause, and good postoperative care. The major causes include incomplete lung re-expansion, pain-induced restriction in chest-wall/diaphragm mobility, prolonged surgery, a complication of pre-existing lung disease, residual effects of some drugs, and iatrogenic causes. We, therefore, recommend the use of postoperative oxygen support and diligent monitoring of vitals in all cases of laparotomy, allowing prompt and timely patient management. Future studies are warranted to explore the prevalence and possible causes of post-laparotomy hypoxia.
PubMed: 36127966
DOI: 10.7759/cureus.28096 -
Frontiers in Pharmacology 2022This present study aims to delineate crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal,...
This present study aims to delineate crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti-, antiulcer effects, and toxicology. Plant extracts attributed dose-dependent protection against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance transverse by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, it causes a concentration-dependent relaxation of both spontaneous and K (80 mM)-induced contraction, Rd.n-Hex and verapamil were relatively potent against K-induced contractions and shifted the Ca concentration-response curves (CRCs) to the right, Rd.Cr and Rd.ETAC shifted the isoprenaline-induced inhibitory CRCs to the left, showing potentiating effect similar to papaverine. Rd.n-Hex showed anti- effect. Extracts and emodin also show an inhibitory effect against H/K-ATPase. showed a gastroprotective and antioxidant effect. Histopathological evaluation showed improvement in cellular architecture and decrease in the expression of inflammatory markers such as cyclooxygenase (COX2), tumor necrosis factor (TNF-α), and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry, ELISA, and western blot techniques. In RT-PCR, it decreases H/K-ATPase mRNA levels. was analyzed for certain safety aspects and exhibited a relative safety profile as no impairment was observed in kidneys, heart, liver, and brain further assisted by biochemical and hematological analysis. Docking studies revealed that emodin against H/K-ATPase pump and voltage gated L-type calcium channel showed E-value of -7.9 and -7.4 kcal/mol, respectively. MD simulations and molecular mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area MMPBSA/GBSA findings are consistent with the and docking results. In conclusion, extracts and its phytoconstituent could be considered a potent antioxidant and anti-inflammatory drug candidates that possess anti-diarrheal, anti-secretary, antispasmodic, anti- and anti-ulcer potential. Toxicity studies were done according to OECD standards 425. It belongs to group 5 (LD50 > 2000 mg/kg), which suggests that it is in the lower toxicity class.
PubMed: 36052146
DOI: 10.3389/fphar.2022.936161 -
Exploration of Targeted Anti-tumor... 2022Neuroendocrine tumor (NET) is a rare tumor that has been observed in different sites such as lungs and throughout the gastrointestinal tract. Clinical features are...
Neuroendocrine tumor (NET) is a rare tumor that has been observed in different sites such as lungs and throughout the gastrointestinal tract. Clinical features are usually non-specific and vary considerably depending upon the location of the tumor. Symptoms are similar to those of common conditions such as peptic ulcer disease, gastritis, irritable bowel syndrome, asthma, etc. Thus, an initial diagnosis of a NET usually occurs at an advanced stage. This report describes a case of pancreatic NET (PNET, grade 2) with liver metastasis in a 37-year-old male which was found to be inoperable due to extensive direct involvement of the proximal jejunal branches and superior mesenteric vein. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate (Lu-DOTATATE) was administered due to the inoperability of primary PNET. Complete resolution of symptoms occurred with three cycles of PRRT.
PubMed: 36045912
DOI: 10.37349/etat.2022.00089 -
BMC Veterinary Research Aug 2022Heterotopic gastric mucosa has been scarcely reported in the veterinary literature. Its presence can be asymptomatic or associated with various clinical signs ranging...
BACKGROUND
Heterotopic gastric mucosa has been scarcely reported in the veterinary literature. Its presence can be asymptomatic or associated with various clinical signs ranging from apathy, vomiting, to abdominal pain. This report illustrates the presence of heterotopic gastric mucosa in the jejunum of an adult dog. It is the first to describe severe anemia, requiring acute blood transfusion, following intestinal hemorrhage caused by heterotopic gastric mucosa.
CASE PRESENTATION
A twelve-year-old, intact male Maltese dog was presented with a history of apathy, vomiting and anemia. The dog was on a strict diet for recurrent diarrhea, food intolerance and skin allergy. Clinical examination revealed severe anemic mucous membranes and painful abdominal palpation. Blood examination confirmed severe regenerative anemia. Ultrasonography showed an intestinal neoplasm, gall bladder sludge and non-homogeneous liver parenchyma. Three-view thoracic radiographs failed to show any metastatic lesions or enlarged lymph nodes. After initial stabilization and blood transfusion, a midline exploratory laparotomy was performed. Three different masses were found in the jejunum. Resection and anastomosis of approximately 40 cm of jejunum was performed, followed by liver and lymph node biopsy and placement of an esophagostomy tube. Two days after surgery the dog started to clinically improve and was discharged from the hospital on the sixth day after surgery. Histopathology revealed the intestinal masses to be heterotopic gastric mucosa associated with intramural cystic distensions, multifocal ulceration and bleeding into the intestinal lumen. Two years after surgery, the dog did not have a recurrence of anemia or gastrointestinal signs.
CONCLUSIONS
This case demonstrates that heterotopic gastric mucosa can be considered one of the differential diagnoses in case of severe anemia due to gastrointestinal hemorrhage and suspected intestinal tumors. Although in most described cases in literature the finding seems to be incidental on necropsy, our report shows that heterotopic gastric mucosa can be the etiology of life-threatening signs. In addition, because no recurrent diarrhea episodes occurred after surgical resection of the ectopic tissue, it is likely that the heterotopic gastric mucosa was the cause of the food intolerance signs in this dog.
Topics: Anemia; Animals; Diarrhea; Dog Diseases; Dogs; Food Intolerance; Gastric Mucosa; Gastrointestinal Hemorrhage; Jejunum; Male; Vomiting
PubMed: 35974373
DOI: 10.1186/s12917-022-03415-0 -
Asian Journal of Endoscopic Surgery Jan 2023Intestinal malrotation (IM) is an abnormality due to a failure of the normal midgut rotation and fixation. We report a case of 46-year-old man with ulcerative colitis...
Intestinal malrotation (IM) is an abnormality due to a failure of the normal midgut rotation and fixation. We report a case of 46-year-old man with ulcerative colitis whose IM was apparent after laparoscopically total proctocolectomy (TPC) followed by ileal-pouch-anal anastomosis (IPAA) and ileostomy. There was no abnormal anatomy except for mobile cecum/ascending colon during the initial operation. Intestinal obstruction occurred after ileostomy closure. The computed tomography scan showed the duodeno-jejunal transition was located in right abdomen, the superior mesenteric vein was located left of the superior mesenteric artery (SMA) and the obstruction point was the distal ileum near the pouch. We performed an ileo-ileo bypass across the ventral side of the SMA to relieve the intestinal obstruction. The patient would have incomplete IM preoperatively, which became apparent by TPC. In case of TPC for mobile colon, anatomy of small intestine should be checked before IPAA.
Topics: Male; Humans; Middle Aged; Proctocolectomy, Restorative; Colitis, Ulcerative; Anastomosis, Surgical; Ileum; Intestinal Obstruction; Postoperative Complications
PubMed: 35950782
DOI: 10.1111/ases.13114