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2.
Surg Today ; 54(4): 347-355, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37610628

RESUMEN

PURPOSE: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). METHODS: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. RESULTS: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. CONCLUSION: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.


Asunto(s)
Colitis Ulcerosa , Neoplasias Asociadas a Colitis , Neoplasias Colorrectales , MicroARNs , Adulto , Humanos , Niño , Metilación de ADN , MicroARNs/genética , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/genética , Biomarcadores , Membrana Mucosa , Neoplasias Colorrectales/genética , Mucosa Intestinal
3.
BMC Pediatr ; 23(1): 452, 2023 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-37689624

RESUMEN

BACKGROUND: Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. CASE PRESENTATION: A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. CONCLUSIONS: Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.


Asunto(s)
Deglución , Nicotina , Femenino , Lactante , Humanos , Duodeno , Servicio de Urgencia en Hospital , Ingestión de Alimentos
4.
Medicina (Kaunas) ; 59(4)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37109767

RESUMEN

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 µg/µL of aflibercept (Af), or 25 µg/µL of bevacizumab (Be), or 10 µg/µL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.


Asunto(s)
Retinopatía Diabética , Edema Macular , Animales , Ratones , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Factores de Crecimiento Endotelial , Edema Macular/etiología , Factor A de Crecimiento Endotelial Vascular , Ratones Endogámicos C57BL , Ranibizumab/uso terapéutico , Bevacizumab/uso terapéutico
5.
J Pediatr Surg ; 58(9): 1663-1669, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37032194

RESUMEN

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital disease. Some CDH infants suffer from gastro-esophageal reflux disease (GERD), even after surgical correction of gastric position. A transpyloric tube (TPT) is inserted into CDH patients under direct observation intraoperatively in some hospitals in Japan to establish early enteral feeding. This strategy avoids gastric expansion to maintain a better respiratory condition. However, it is unclear whether the strategy has a secure effect for patient prognosis. This study aimed to evaluate the effectiveness of intraoperative TPT insertion on enteral feeding and postoperative weight gain. METHODS: The Japanese CDH Study Group database was used to identify infants with CDH born between 2011 and 2016, who were then divided into two groups: the TPT group and gastric tube (GT) group. In the TPT group, infants underwent intraoperative TPT insertion; postoperative insertion/extraction of TPT was irrelevant to the analysis. Weight growth velocity (WGV) was calculated using the exponential model. Subgroup analysis was performed using Kitano's gastric position classification. RESULTS: We analyzed 204 infants, of which 99 and 105 were in the TPT and GT groups, respectively. Enteral nutrition (EN) in the TPT and GT groups was 52 ± 39 and 44 ± 41 kcal/kg/day (p = 0.17) at age 14 days (EN14), respectively, and 83 ± 40 and 78 ± 45 kcal/kg/day (p = 0.46) at age 21 days (EN21), respectively. WGV30 (WGV from day 0 to day 30) in the TPT and GT groups was 2.3 ± 3.0 and 2.8 ± 3.8 g/kg/day (p = 0.30), respectively, and WGV60 (WGV from day 0 to day 60) was 5.1 ± 2.3 and 6.0 ± 2.5 g/kg/day (p = 0.03), respectively. In infants with Kitano's Grade 2 + 3, EN14 in the TPT and GT groups was 38 ± 35 and 29 ± 35 kcal/kg/day (p = 0.24), respectively, EN21 was 73 ± 40 and 58 ± 45 kcal/kg/day (p = 0.13), respectively, WGV30 was 2.3 ± 3.2 and 2.0 ± 4.3 g/kg/day (p = 0.76), respectively, and WGV60 was 4.6 ± 2.3 and 5.2 ± 2.3 g/kg/day (p = 0.30), respectively. CONCLUSION: Intraoperative TPT insertion did not improve nutritional intake and WGV30. WGV60 in TPT was less than that in GT. In Grade 2 + 3 subgroup analysis, TPT also had no advantage. We could not recommend routine TPT insertion at surgery. LEVEL OF EVIDENCE: III.


Asunto(s)
Nutrición Enteral , Reflujo Gastroesofágico , Hernias Diafragmáticas Congénitas , Intubación Gastrointestinal , Humanos , Lactante , Recién Nacido , Pueblos del Este de Asia , Nutrición Enteral/instrumentación , Nutrición Enteral/métodos , Reflujo Gastroesofágico/etiología , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/cirugía , Estudios Retrospectivos , Periodo Intraoperatorio , Píloro/cirugía , Intubación Gastrointestinal/instrumentación , Intubación Gastrointestinal/métodos
7.
Surg Today ; 53(4): 483-489, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36219246

RESUMEN

PURPOSE: To assess the severity of preoperative myopenia and myosteatosis in pediatric patients with inflammatory bowel disease (IBD) and examine their impact on postoperative complications. METHODS: The subjects of this retrospective study were 30 pediatric patients with IBD (22 with ulcerative colitis (UC) and 8 with Crohn's disease (CD)) and 67 age-matched controls. Preoperative body mass index (BMI), psoas muscle index (PMI), and intramuscular adipose tissue content were compared between the patient groups, to investigate their association with postoperative complications. RESULTS: BMI and PMI were significantly lower in the IBD patients than in the controls (p < 0.0001, p < 0.0001, respectively). CD was associated with significantly lower BMI and PMI (p = 0.01, p = 0.01, respectively) than UC. Intramuscular adipose tissue content was comparable between the IBD patients and the controls and between the UC and CD patients. There were no significant differences among the three indices in relation to the presence or absence of postoperative complications in patients with IBD. When limited to surgical site infection (SSI), only PMI was significantly lower in the patients with SSI than in those without SSI (p = 0.04). CONCLUSIONS: Although BMI and PMI were lower preoperatively in pediatric IBD patients than in controls, only myopenia seemed to affect the development of SSI.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/complicaciones , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/cirugía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/cirugía , Infección de la Herida Quirúrgica , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
8.
Arch Dis Child Fetal Neonatal Ed ; 108(1): 69-76, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35940871

RESUMEN

OBJECTIVE: Remote ischaemic conditioning (RIC) improves the outcome of experimental necrotising enterocolitis (NEC) by preserving intestinal microcirculation. The feasibility and safety of RIC in preterm infants with NEC are unknown. The study aimed to assess the feasibility and safety of RIC in preterm infants with suspected or confirmed NEC. DESIGN: Phase I non-randomised pilot study conducted in three steps: step A to determine the safe duration of limb ischaemia (up to 4 min); step B to assess the safety of 4 repeated cycles of ischaemia-reperfusion at the maximum tolerated duration of ischaemia determined in step A; step C to assess the safety of applying 4 cycles of ischaemia-reperfusion on two consecutive days. SETTING: Level III neonatal intensive care unit, The Hospital for Sick Children (Toronto, Canada). PATIENTS: Fifteen preterm infants born between 22 and 33 weeks gestational age. INTERVENTION: Four cycles of ischaemia (varying duration) applied to the limb via a manual sphygmomanometer, followed by reperfusion (4 min) and rest (5 min), repeated on two consecutive days. OUTCOMES: The primary outcomes were (1) feasibility defined as RIC being performed as planned in the protocol, and (2) safety defined as perfusion returning to baseline within 4 min after cuff deflation. RESULTS: Four cycles/day of limb ischaemia (4 min) followed by reperfusion (4 min) and a 5 min gap, repeated on two consecutive days was feasible and safe in all neonates with suspected or confirmed NEC. CONCLUSIONS: This study is pivotal for designing a future randomised controlled trial to assess the efficacy of RIC in preterm infants with NEC. TRIAL REGISTRATION NUMBER: NCT03860701.


Asunto(s)
Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Niño , Recién Nacido , Humanos , Recien Nacido Prematuro , Estudios de Factibilidad , Proyectos Piloto , Isquemia
9.
Pediatr Surg Int ; 39(1): 4, 2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36441244

RESUMEN

PURPOSE: To develop a predictive score for small diaphragmatic defects in infants with congenital diaphragmatic hernia (CDH) for determining thoracoscopic surgery indication. METHODS: The Japanese CDH Study Group cohort was randomly divided into derivation (n = 397) and validation (n = 396) datasets. Using logistic regression, a prediction model and weighted scoring system for small diaphragmatic defects were created from derivation dataset and validated with validation dataset. RESULTS: Six weighted variables were selected: no hydramnios, 1 point; 1 min Apgar score of 5-10, 1 point; apex type of the lung (left lung is detected radiographically in apex area), 1 point; oxygenation index < 8, 1 point; abdominal nasogastric tube (tip of the nasogastric tube is detected radiographically in the abdominal area), 2 points; no right-to-left flow of ductus arteriosus, 1 point. In validation dataset, rates of small diaphragmatic defects for Possible (0-3 points), Probable (4-5 points), and Definite (6-7 points) groups were 36%, 81%, and 94%, respectively (p < 0.001). Additionally, sensitivity, specificity, positive predictive value, and C statistics were 0.78, 0.79, 0.88, 0.76, and 0.45, 0.94, 0.94, 0.70 for Probable and Definite groups, respectively. CONCLUSION: Our scoring system effectively predicted small diaphragmatic defects in infants with CDH.


Asunto(s)
Conducto Arterioso Permeable , Hernias Diafragmáticas Congénitas , Lactante , Humanos , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/cirugía , Análisis de los Gases de la Sangre , Probabilidad
10.
Pediatr Surg Int ; 38(12): 1873-1880, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36138323

RESUMEN

PURPOSE: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. METHODS: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. RESULTS: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p < 0.001), shorter mechanical ventilation (11 vs. 19 days, p < 0.001), shorter hospitalization (38 vs. 59 days, p < 0.001), and lower recurrence rate (p = 0.002) than the AD group. A multivariate analysis showed that BD (adjusted odds ratio, 3.68; 95% confidence interval 1.02-13.30) was a favorable prognostic factor for the 90-day survival. CONCLUSION: The assessment of the NG tube position revealed it to be a reliable prognostic factor of left-sided isolated CDH. Therefore, it should be included as a routine assessment.


Asunto(s)
Hernias Diafragmáticas Congénitas , Recién Nacido , Embarazo , Femenino , Humanos , Hernias Diafragmáticas Congénitas/cirugía , Estudios Retrospectivos , Pronóstico , Diagnóstico Prenatal , Intubación Gastrointestinal , Ultrasonografía Prenatal , Edad Gestacional
11.
Children (Basel) ; 9(6)2022 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-35740795

RESUMEN

BACKGROUND: Treatment modalities for neonates with congenital diaphragmatic hernia (CDH) have greatly improved in recent years, with a concomitant increase in survival. However, long-term outcomes restrict the identification of optimal care pathways for CDH survivors in adolescence and adulthood. Therefore, we evaluated the long-term outcomes within the Japanese CDH Study Group (JCDHSG). METHODS: Participants were born with CDH between 2006 and 2018 according to the JCDHSG. Participants were enrolled in the database at 1.5, 3, 6, and 12 years old. Follow-up items included long-term complications, operations for long-term complication, and home medical care. RESULTS: A total of 747 patients were included in this study, with 626 survivors (83.8%) and 121 non-survivors (16.2%). At 1.5, 3, 6, and 12 years old, 45.4%, 36.5%, 34.8%, and 43.6% developed complications, and 20.1%, 14.7%, 11.5%, and 5.1% of participants required home care, respectively. Recurrence, pneumonia, pneumothorax, gastroesophageal reflux disease, and intestinal obstruction decreased with age, and thoracic deformity increased with age. CONCLUSIONS: As CDH survival rates improve, there is a need for continued research and fine-tuning of long-term care to optimize appropriate surveillance and long-term follow-up.

12.
Oncol Lett ; 23(4): 136, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35317024

RESUMEN

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is upregulated in various tumors, and several studies have demonstrated the role of TPX2 as a prognostic marker in cancer. However, the function of TPX2 in neuroblastoma (NB) has not been completely elucidated. In the present study, the clinical significance and functional role of TPX2 in NB was investigated. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-NB dataset was used. A total of 43 patients with NB were enrolled in the present study as the validation set. After evaluating the prognostic role of TPX2, the combined predictive effect of TPX2 and MYCN proto-oncogene bHLH transcription factor (MYCN) gene amplification was assessed. Double immunofluorescence staining for TPX2 and N-Myc was used to analyze colocalization, and multiple cell function tests were performed by means of in vitro experiments to elucidate the functional role of TPX2 using RNA interference technology in NB cell lines. In both the TARGET-NB set and the validation set, it was found that upregulated of TPX2 was significantly associated with poor overall survival (OS) in patients with NB. The expression of TPX2 was higher in NB patients with MYCN gene amplification, and NB patients with high TPX2 expression and MYCN gene amplification had the poorest OS compared with patients with low TPX2 expression or a single copy of MYCN. In vitro experiments indicated that TPX2 positively regulated cell proliferation and the cell cycle, and promoted cell survival by increasing the resistance to apoptosis. The colocalization of TPX2 with N-Myc in NB cells and tissue was observed. The findings of the present study indicate that TPX2 plays an oncogenic role in NB development and may be a potential prognostic indicator in patients with NB.

13.
Oncol Lett ; 22(1): 523, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34025790

RESUMEN

The overall prognosis of advanced/metastatic gastric cancer (GC) remains poor despite the development of pharmacotherapy. Therefore, other treatment options, such as complementary and alternative medicine, should be considered to overcome this aggressive malignancy. Andrographis, which is a generally unharmful botanical compound, has gained increasing interest for its anticancer effects in multiple malignancies via the regulation of cancer progression-associated signaling pathways. In the present study, a series of in vitro experiments (cell proliferation, colony formation and apoptosis assays) was designed to elucidate the antitumor potential and mechanism of Andrographis in GC cells. The present study demonstrated that Andrographis exerted antitumor effects in GC cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Furthermore, it was demonstrated that the expression levels of the ferroptosis-associated genes heme oxygenase-1, glutamate-cysteine ligase catalytic and glutamate-cysteine ligase modifier were significantly upregulated after Andrographis treatment in both GC cell lines in reverse transcription-quantitative PCR experiments (P<0.05); this finding was further confirmed by immunoblotting assays (P<0.05). In conclusion, to the best of our knowledge, the present study was the first to demonstrate that Andrographis possessed antitumor properties by altering the expression levels of ferroptosis-associated genes, thereby providing novel insights into the potential of Andrographis as an adjunctive treatment option for patients with metastatic GC.

14.
Bio Protoc ; 11(5): e3937, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33796611

RESUMEN

This protocol describes a novel technique to investigate the microcirculation dynamics underlying the pathology in the small intestine of neonatal mice using two-photon laser-scanning microscopy (TPLSM). Recent technological advances in multi-photon microscopy allow intravital analysis of different organs such as the liver, brain and intestine. Despite these advances, live visualization and analysis of the small intestine in neonatal rodents remain technically challenging. We herein provide a detailed description of a novel method to capture high resolution and stable images of the small intestine in neonatal mice as early as postnatal day 0. This imaging technique allows a comprehensive understanding of the development and blood flow dynamics in small intestine microcirculation.

16.
Pediatr Surg Int ; 37(3): 347-352, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33580271

RESUMEN

PURPOSE: Monitoring disease progression is crucial to improve the outcome of necrotizing enterocolitis (NEC). A previous study indicates that intestinal wall flow velocity was reduced in NEC pups from the initial stages of the disease. This study aims to investigate whether splanchnic perfusion via the superior mesenteric artery (SMA) (i) is altered during NEC development and (ii) can be used as a monitoring tool to assess disease progression. METHODS: NEC was induced in C57BL/6 mice via gavage feeding of formula, hypoxia, and oral lipopolysaccharide, from postnatal day 5 (P5) to P9 (AUP: 32,238). Breastfed littermates served as controls. Doppler ultrasound (U/S) of bowel loops was performed daily. Intestinal wall perfusion was calculated as average flow velocity (mm/s) of multiple abdominal regions. Groups were compared using one-way ANOVA. RESULTS: The SMA flow velocity was not altered during the initial stage of NEC development, but become significantly reduced at P8 when the intestinal disease was more advanced. These changes occurred concomitantly with an increase in heart rate. CONCLUSIONS: NEC is associated with intestinal hypo-perfusion at the periphery and flow in the SMA is reduced during the later stages of disease indicating the presence of intestinal epithelium damage. This study contributes to understanding NEC pathophysiology and illustrates the value of Doppler U/S in monitoring disease progression.


Asunto(s)
Enterocolitis Necrotizante/fisiopatología , Arteria Mesentérica Superior/diagnóstico por imagen , Arteria Mesentérica Superior/fisiología , Ultrasonografía Doppler , Animales , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Humanos , Recién Nacido , Enfermedades del Recién Nacido , Mucosa Intestinal/fisiopatología , Intestinos/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Perfusión
17.
FASEB J ; 35(1): e21265, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33373067

RESUMEN

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases affecting premature infants. It has been shown that NEC is associated with disrupted intestinal barrier and dysregulated endoplasmic reticulum (ER)-stress response. It has also been shown that stem cells derived from amniotic fluid (AFSC) rescued intestinal injury in experimental NEC. Herein, we hypothesized that the beneficial effects of AFSC in the injured intestine are due to the restoration of intestinal barrier function. We evaluated intestinal barrier function using an ex vivo intestinal organoid model of NEC. We found that AFSC restored the expression and localization of tight junction proteins in intestinal organoids, and subsequently decreased epithelial permeability. AFSC rescued tight junction expression by inducing a protective ER stress response that prevents epithelial cell apoptosis in injured intestinal organoids. Finally, we validated these results in our experimental mouse model of NEC and confirmed that AFSC induced sustained ER stress and prevented intestinal apoptosis. This response led to the restoration of tight junction expression and localization, which subsequently reduced intestinal permeability in NEC pups. These findings confirm that intestinal barrier function is disrupted during NEC intestinal injury, and further demonstrate the disruption can be reversed by the administration of AFSC through the activation of the ER stress pathway. This study provides insight into the pathogenesis of NEC and highlights potential therapeutic targets for the treatment of NEC.


Asunto(s)
Líquido Amniótico/metabolismo , Estrés del Retículo Endoplásmico , Enterocolitis Necrotizante/metabolismo , Mucosa Intestinal/metabolismo , Células Madre/metabolismo , Uniones Estrechas/metabolismo , Animales , Apoptosis , Enterocolitis Necrotizante/patología , Mucosa Intestinal/patología , Ratones , Organoides/metabolismo , Organoides/patología , Permeabilidad , Ratas , Células Madre/patología , Uniones Estrechas/patología
18.
J Gastrointest Surg ; 25(8): 2047-2054, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33140320

RESUMEN

PURPOSE: We aimed to identify predictive factors for the development of chronic pouchitis after ileal pouch-anal anastomosis in patients with ulcerative colitis. METHODS: Three hundred eighty-seven patients who underwent ileal pouch-anal anastomosis for diagnosis of ulcerative colitis from January 2002 to March 2019 were included in this retrospective analysis. RESULTS: Of 115 patients with pouchitis, 40 patients exhibited acute pouchitis, and 75 patients exhibited chronic pouchitis. Of 75 patients with chronic pouchitis, 11 patients were diagnosed with chronic antibiotic-refractory pouchitis. Multivariate analysis revealed that early pouchitis onset and modified Pouchitis Disease Activity Index score ≥ 7 were independent predictive factors for chronic pouchitis (p = 0.0004 and p = 0.029, respectively). Mean onset of pouchitis after intestinal continuity was significantly earlier in patients with chronic pouchitis than in patients with acute pouchitis (acute pouchitis vs. chronic pouchitis: 3.72 ± 2.98 years vs. 1.85 ± 2.40 years, p < 0.0001). Total modified Pouchitis Disease Activity Index score was significantly higher in patients with chronic pouchitis than in patients with acute pouchitis (acute pouchitis vs. chronic pouchitis: 5.9 ± 1.2 vs. 6.9 ± 1.6, p = 0.0020). CONCLUSION: Patients with ulcerative colitis were more likely to develop chronic pouchitis if they exhibited early onset or severe disease activity at onset. Evaluation of both factors can aid in early treatment decisions to alleviate chronic pouchitis.


Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Reservoritis , Proctocolectomía Restauradora , Anastomosis Quirúrgica/efectos adversos , Colitis Ulcerosa/cirugía , Reservorios Cólicos/efectos adversos , Humanos , Reservoritis/diagnóstico , Reservoritis/tratamiento farmacológico , Reservoritis/etiología , Proctocolectomía Restauradora/efectos adversos , Estudios Retrospectivos
19.
Nat Commun ; 11(1): 4950, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009377

RESUMEN

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.


Asunto(s)
Enterocolitis Necrotizante/patología , Intestinos/irrigación sanguínea , Intestinos/patología , Isquemia/patología , Microcirculación , Animales , Enterocitos/patología , Humanos , Hipoxia , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Microvellosidades/patología , Microvellosidades/ultraestructura
20.
Pediatr Surg Int ; 36(12): 1437-1442, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33068141

RESUMEN

PURPOSE: Midgut volvulus is associated with intestinal ischemia/reperfusion (IR) injury and can progress to severe intestinal damage. Remote ischemic conditioning (RIC) reduces IR-induced injury in distant organs. The aim of this study was to investigate whether RIC protects the intestine from IR injury. METHODS: We investigated intestinal IR injury in 3 weeks old SD rats. Animals underwent: (i) sham laparotomy, (ii) intestinal IR injury, (iii) intestinal IR + RIC during ischemia, or (iv) intestinal IR + RIC after reperfusion. Intestinal IR injury was achieved by 45 min occlusion of superior mesenteric artery followed by de-occlusion. RIC was administered via four cycles of 5 min of hind limb ischemia followed by 5 min reperfusion. Animals were sacrificed 24 h after surgery and the ileum was harvested for evaluation. RESULTS: Intestinal injury was present after IR. However, this injury was reduced in both IR + RIC groups. Expression of inflammatory cytokine IL6 was lower in IR + RIC groups compared to IR alone. Carbonyl protein was also significantly lower in IR + RIC compared to IR, indicating lower oxidative stress in both IR + RIC groups. CONCLUSION: Remote ischemic conditioning attenuated intestinal injury, inflammation, and oxidative stress in experimental intestinal ischemia/reperfusion injury. Remote ischemic conditioning may be useful in children with midgut volvulus to reduce the intestinal injury. LEVEL OF EVIDENCE: Experimental study. TYPE OF STUDY: Animal experiment.


Asunto(s)
Anomalías del Sistema Digestivo/fisiopatología , Vólvulo Intestinal/fisiopatología , Intestinos/fisiopatología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/fisiopatología , Animales , Anomalías del Sistema Digestivo/complicaciones , Modelos Animales de Enfermedad , Vólvulo Intestinal/complicaciones , Masculino , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/etiología
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