• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.4
• /
• pp.261-272
• /
• 2021

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKβ, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.20 no.1
• /
• pp.55-60
• /
• 2017

Intestinal hypoganglionosis is a rare innervation disorder that provides numerous nutritional, medical and surgical challenges. In this case report, we present a case of a newborn with intestinal hypoganglionosis leading to intestinal failure and intestinal failure-associated liver disease who responded to $Omegaven^{TM}$, a fat emulsion comprised of omega-3 fatty acids. $Omegaven^{TM}$ has been shown to be beneficial in the management of cholestatic liver injury. Clinical success with $Omegaven^{TM}$ was seen in this patient with a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and complete resolution of cholestasis with a direct bilirubin of zero within two weeks of initiation of $Omegaven^{TM}$. No current guidelines for the diagnosis and management of hypoganglionosis are available. We recommend a multidisciplinary approach and the use of novel therapies such as fat emulsions composed of omega-3 fatty acids for improved patient outcomes. Appropriate compassionate use protocols should be obtained from the Food and Drug Administration prior to initiation of $Omegaven^{TM}$.

• Journal of Trauma and Injury
• /
• v.29 no.2
• /
• pp.56-59
• /
• 2016

Patients with pelvic bone fractures with gastrointestinal perforations are reported in 4.4% of the cases and in very rare cases jejunum (0.15) is involved. However, intestinal perforations are often undiagnosed on the first examination before peritonitis is evident. We are presenting a report where a patient with anteroposterior compression injury, who was expected to undergo an internal fixation procedure, did not show any jejunum perforations on abdominal CT or other physical exams but was found on abdominal CT 1 week after right before surgery, therefore excision and anastomosis surgery, pelvic open reduction and internal fixation was simultaneously done with favorable results. In our case, we present a 61 year old male patient with liver trauma, adhesion at the abdominal cavity, with a past history of gallbladder excision, but without abdominal pain, fever, or infection symptoms. Therefore, this was a case that was difficult to initially diagnose the patient with jejunum perforation and peritonitis. The diagnosis was further supported during laparotomy when peritonitis around the area of intestinal perforation was observed. Generally, it is understood that pelvic bone fracture surgery is not immediately done on patients with peritonitis. However, this kind of patient who had peritonitis with intestinal adhesion and other complications could undergo surgery immediately as infection or other related symptoms did not coexist and the patient was rather stable, and as a result the treatment was successful.

• Biomolecules & Therapeutics
• /
• v.29 no.2
• /
• pp.175-183
• /
• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Journal of Trauma and Injury
• /
• v.19 no.1
• /
• pp.14-20
• /
• 2006

Purpose: Although hypothermia has been used in many clinical situations, such as post cardiopulmonary resuscitation, stroke, traumatic brain injury, septic shock, and hemorrhagic shock, the mechanism by which it works has not been clearly elucidated. We aimed to evaluate the effect of hypothermia on the plasma nitric oxide (NO) concentration, lung iNOS expression, and histologic changes in intestinal ischemia-reperfusion (IR). Method: Male Sprague-Dawley rats were randomly divided into the hypothermia group (HT, n=8, $27{\sim}30^{\circ}C$) and the normothermia group (NT, n=8, $36{\sim}37^{\circ}C$). They underwent 30 min of intestinal ischemia by clamping the superior mesenteric artery, which was followed by 1.5 h of reperfusion. They were then sacrificed. The acute lung injury (ALI) score, the plasma NO concentration, and lung iNOS gene expression were measured. Results: Compared with the HT group, the NT group showed severe infiltrations of inflammatrory cells, alveolar hemorrhages, and interstitial hypertrophies in lung tissues. There were significant differences in the ALI scores between the NT and the HT groups ($8.7{\pm}1.5/HPF$ in NT vs $5.8{\pm}1.2/HPF$ in HT, p=0.008). Although the plasma NO concentration was slightly lower in the HT group, there was no significant difference between the two groups ($0.80{\pm}0.24{\mu}mol/L$ in NT vs $0.75{\pm}0.30{\mu}mol/L$ in HT, p=0.917). Lung iNOS gene expression was stronger in the NT group than in the HT group. The band density of the expression of iNOS in lung tissues was significantly increased in the NT group compared to the HT group ($5.54{\pm}2.75$ in NT vs$0.08{\pm}0.52$ in HT, p=0.002). Conclusions: This study showed that hypothermia in intestinal IR reduces inflammatory responses, ALI scores, and iNOS gene expression in lung tissues. There was no significant effect of hypothermia on the plasma NO concentration.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.1
• /
• pp.1-7
• /
• 2015

Our previous study has shown berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. In this study, we explored the regulatory effects of berberine on Toll-like receptors during the intestinal mucosal damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR 9, the activity of nuclear factor-kappa B ($NF-{\kappa}B$), the levels of selected cytokines and chemokines, percentage of cell death in intestinal epithelial cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after CLP. Results showed that the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) level were significantly lower in berberine-treated rats compared to the control animals. Conversely, the expression level of tight junction proteins, percentage of cell death in intestinal epithelial cells and the mucosal permeability were significantly higher in berberine-treated rats. The mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by berberine treatment. Our results indicate that pretreatment with berberine attenuates tissue injury and protects the intestinal mucosal barrier in early phase of sepsis and this may possibly have been mediated through the TLRs pathway.

• Journal of Trauma and Injury
• /
• v.35 no.2
• /
• pp.118-122
• /
• 2022

The usual cause of penetrating thoracoabdominal injuries with evisceration are stab wounds with knives and other sharp weapons used during fights and conflicts. Evisceration of the abdominal viscera as a result of trauma, with its attendant morbidity and mortality, requires early intervention. Gunshot wounds can also cause penetrating thoracoabdominal injuries. We report the case of a 52-year-old male patient, a worker at a timber-processing factory, who was assaulted with a chainsaw by his colleague following a disagreement. He was seen at the accident and emergency department of Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria with a thoracoabdominal injury about 1.5 hours after the attack. He had a left thoracoabdominal laceration with abdominal evisceration and an open left pneumothorax. He was managed operatively, made a full recovery, and was discharged 16 days after admission. He was readmitted 4 months after the initial surgery with acute intestinal obstruction secondary to adhesions. He underwent exploratory laparotomy and adhesiolysis. He made an uneventful recovery and was discharged on the 9th postoperative day for subsequent follow-up.

• Journal of Trauma and Injury
• /
• v.27 no.2
• /
• pp.38-42
• /
• 2014

Traumatic diaphragmatic rupture is quite uncommon and rarely lethal injury. However, delayed presentation between the injury and the diagnosis can cause a life-threatening condition with various complications such as intestinal hernia, obstruction, strangulation, respiratory distress. Here, we present a case of delayed presentation of traumatic diaphragmatic rupture in a 51-year-old man, and then discuss about the clinical implication of delayed presentation of diaphragmatic rupture with a review.

• Journal of Korean Neurosurgical Society
• /
• v.47 no.3
• /
• pp.224-227
• /
• 2010

Small bowel injury resulting from unforeseen penetration of the anterior annulus fibrosus and longitudinal ligament is a rare complication of lumbar microdiscectomy. The patient complained of abdominal tenderness and distention immediately after microdiscectomy for L4-5 and L5-S1 disc herniation. Using abdominal computed tomography, we found several foci of air overlying the anterior aspect of the vertebral body at the L5-S1 level. Segmental resection of the small bowel including small tears and primary anastomosis of the jejunum were performed. Here, we present a case of intestinal perforation after lumbar microdiscectomy and discuss technical methods to prevent this complication with a review of literature.

• Journal of Animal Science and Technology
• /
• v.62 no.3
• /
• pp.348-355
• /
• 2020

Cyclophosphamide, a cytotoxic anticancer agent, induces immunosuppression and has several adverse effects. N-acetylcysteine alleviates oxidative stress, liver injury, and intestinal tissue damage. The present study examined whether N-acetylcysteine modulates the adverse effects of cyclophosphamide in pigs. Miniature pigs (n = 15) were used as an experimental model to evaluate the effects of N-acetylcysteine treatment on immune reactions, liver injury, and oxidative stress after cyclophosphamide challenge. Corn-soybean meal based dietary treatments were as follows: control diet with either saline injection, cyclophosphamide injection, or 0.5% N-acetylcysteine and cyclophosphamide injection. N-acetylcysteine increased the number of immune cells and decreased TNF-α production after cyclophosphamide injection and decreased TNF-α, IFN-γ, NF-κB, and IL-8 expression and increased IL-10 expression in peripheral blood mononuclear cells. Serum levels of alanine transaminase and aspartate aminotransferase decreased, superoxide dismutase activity increased, and malondialdehyde activity decreased following N-acetylcysteine treatment after cyclophosphamide injection. N-acetylcysteine decreases immunosuppression, liver injury, and oxidative stress in cyclophosphamide-challenged miniature pigs. The present study suggests that N-acetylcysteine has therapeutic application in livestock for modulating immune reactions, liver injury, and oxidative stress.