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1.
Pediatr Blood Cancer ; 71(8): e31114, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38840423

RESUMEN

Acute appendicitis (AA) in pediatric patients with acute leukemia mandates prompt treatment. Diagnosis presents challenges, relying on clinical and radiological assessments, often leading to treatment delays that may disrupt leukemia management. Our study on 14 such cases underscores the pivotal role of swift intervention. While conservative AA treatment may pose no risk to healthy children, our findings mandate the performance of laparoscopic appendectomy within 24 hours of diagnosis. This strategy yielded successful surgical outcomes while ensuring uninterrupted leukemia care. Our experience contributes important insights to the limited understanding of navigating this complex clinical scenario.


Asunto(s)
Apendicectomía , Apendicitis , Humanos , Apendicitis/cirugía , Apendicitis/terapia , Niño , Masculino , Femenino , Adolescente , Preescolar , Enfermedad Aguda , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Estudios Retrospectivos , Laparoscopía , Pronóstico
2.
Acta Paediatr ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949557

RESUMEN

AIM: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. METHODS: A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). RESULTS: Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. CONCLUSION: Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

3.
Acta Paediatr ; 112(9): 1870-1876, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37266967

RESUMEN

AIM: Demand for upper gastrointestinal contrast series (UGI) to investigate bilious vomiting (BV) has increased in recent years, mostly due to greater awareness of the need to rule out malrotation and midgut volvulus (MGV). We aimed to examine predictive value of clinical parameters in the management of healthy neonates presenting with BV and re-assess the role of UGI in their management. METHODS: A retrospective cohort study including medical, imaging and surgical data of neonates who underwent UGI due to BV. RESULTS: A total of 157 term neonates, eight neonates (5.1%) had confirmed surgical diagnosis of malrotation, five of them had malrotation with MGV, including two neonates who underwent extensive intestinal resection due to necrosis. Neonates with a combination of abnormal plain radiograph and abdominal distention had 10 times higher odds of malrotation diagnosis, adjusting for age at first BV (p = 0.017). Neonates with a combination of abnormal plain radiograph, abdominal distention and abdominal tenderness had 25 times higher odds of MGV (p = 0.002). CONCLUSION: This study reaffirms the role of UGI as the current main diagnostic tool for malrotation and MGV. Physical examination and plain radiograph findings can help but cannot substitute UGI study.


Asunto(s)
Anomalías del Sistema Digestivo , Vólvulo Intestinal , Recién Nacido , Humanos , Estudios Retrospectivos , Vómitos/etiología , Radiografía , Anomalías del Sistema Digestivo/diagnóstico , Anomalías del Sistema Digestivo/diagnóstico por imagen , Vólvulo Intestinal/diagnóstico , Vólvulo Intestinal/diagnóstico por imagen
4.
Pediatr Surg Int ; 40(1): 23, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38108924

RESUMEN

PURPOSE: Notch and Wnt/ß-catenin signaling are responsible for regulation of intestinal stem cells (ISCs) proliferation and differentiation. The purpose of the study was to evaluate Wnt/ß-catenin and Notch signaling roles in regulation of ISC differentiation following ischemia-reperfusion (IR) injury in a rat. METHODS: Rats were assigned into two groups: Sham rats underwent laparotomy without vascular intervention and IR rats underwent occlusion of SMA and portal vein for 20 min followed by 48 h of reperfusion. Wnt/ß-catenin and Notch-related gene expression were determined using Real-Time PCR. Enterocyte proliferation, differentiation and Wnt-related proteins were determined by immunohistochemistry. RESULTS: IR rats demonstrated a significant decrease in ß-catenin gene expression, a decrease in cyclin D1 and ß-catenin positive cells in jejunum and ileum compared to Sham rats. IR rats demonstrated a significant increase in Notch-related gene expression in jejunum and ileum compared to Sham rats. The number of secretory cells was higher mainly in the jejunum and number of absorptive cells was significantly lower in jejunum and lower in ileum in IR rats compared to Sham rats. CONCLUSIONS: Intestinal stem-cell differentiation is toward secretory cells 48 h after IR injury; however, Wnt/ß-catenin pathway inhibition and Notch-related gene expression stimulation suggest crosstalk between pathways.


Asunto(s)
Daño por Reperfusión , beta Catenina , Animales , Ratas , beta Catenina/genética , Intestinos , Diferenciación Celular , Células Madre
5.
Pediatr Surg Int ; 39(1): 80, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36631569

RESUMEN

PURPOSE: Nowadays, the standard therapy for patients with short bowel syndrome is parenteral nutrition (PN). Various growth factors have been tested to achieve weaning from prolonged PN administration. We evaluated the effect of hepatocyte growth factor (HGF) on structural intestinal adaptation and cell proliferation in a rat model of SBS. METHODS: Thirty Sprague-Dawley rats were divided into three groups; group A rats (sham) underwent bowel transection, group B rats underwent a 75% bowel resection, and group C rats underwent the same procedure but were treated postoperatively with HGF. Histopathologic parameters of intestinal adaptation were determined, while microarray and rt-PCR analyses of ileal RNA were also performed. RESULTS: Treatment with HGF resulted in significant increase in body weight, while the jejunal and ileal villus height and crypt depth were increased in HGF rats (36%, p < 0.05 and 27%, p < 0.05 respectively). Enterocyte proliferation was also significantly increased in HGF rats (21% p < 0.05). Microarray and quantitative rt-PCR analyses showed that the genes hgfac, rac 1, cdc42, and akt 1 were more than twofold up-regulated after HGF treatment. CONCLUSION: HGF emerges as a growth factor that enhances intestinal adaptation. The future use of HGF may potentially reduce the requirement for PN in SBS patients.


Asunto(s)
Adaptación Fisiológica , Factor de Crecimiento de Hepatocito , Síndrome del Intestino Corto , Animales , Ratas , Modelos Animales de Enfermedad , Factor de Crecimiento de Hepatocito/farmacología , Factor de Crecimiento de Hepatocito/uso terapéutico , Mucosa Intestinal/metabolismo , Intestinos/patología , Modelos Teóricos , Ratas Sprague-Dawley , Síndrome del Intestino Corto/tratamiento farmacológico , Síndrome del Intestino Corto/metabolismo
6.
Pediatr Surg Int ; 39(1): 34, 2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36462084

RESUMEN

PURPOSE: Following extensive bowel resection, many children with short bowel syndrome (SBS) are routinely offered a placement of gastrostomy tube (G-tube) for feeding. This nutritional pathway is aimed to accommodate the gastric and small bowel motor disturbances related to SBS, and to promote weaning off parenteral nutrition (PN) to achieve enteral autonomy (EA). The aim of this study was to investigate the effect of gastrostomy feeding in outcomes of children with SBS. METHODS: A retrospective cohort of all SBS children managed at our multidisciplinary Intestinal Rehabilitation Center as part of an Intestinal Rehabilitation Program. SBS was defined as PN dependence for more than six weeks following extensive bowel resection. Patients treated with G-tube feeding were compared with patients without G-tube in terms of PN duration, reaching EA, physical development, and surgical parameters. RESULTS: A total of 36 SBS patients diagnosed between 2003 and 2022 were included. The most common etiologies included congenital intestinal atresia (31%) and necrotizing enterocolitis (25%). SBS-G-tube (group A) contained 20 children, and SBS (group B) contained 16 children. A total of 21 children reached EA (58%); ten from group A (50%), and 11 from group B (69%) (p > 0.05). Within EA patients, mean PN duration was 49 ± 44 months in group A, and 24 ± 33 months in group B (p > 0.05). Patients who reached EA had 22% longer residual small bowel when compared with PN-dependent patients (p = 0.003). However, the outcomes were adjusted for residual small and large bowel length and percentages, a residual ileocecal valve, and a colon in continuity with no differences between the groups. Two-thirds of children from group A reported G-tube related complications (mechanical, bleeding, or infections). We did not find differences in mean height and weight percentiles between the groups (p > 0.05). CONCLUSION: We did not find significant advantage of gastrostomy feeding in reaching EA. Because there are surgical and mechanical complications related to this procedure, further prospective studies are required to determine G-tube relevance for children with SBS.


Asunto(s)
Síndrome del Intestino Corto , Niño , Humanos , Recién Nacido , Nutrición Enteral , Gastrostomía , Estudios Retrospectivos , Intestinos
7.
Pediatr Surg Int ; 38(12): 1671-1680, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36114863

RESUMEN

PURPOSE: The incidence of pediatric onset ulcerative colitis (UC) is increasing, with increasing rate of children eventually requiring surgical treatment. Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment. Although transanal IPAA (ta-IPAA) is becoming widely accepted for adult UC patients, data regarding this procedure in children are scarce. Nevertheless, some adult publications also include patients under 18 years old. This systematic review and meta-analysis aimed to summarize surgical and functional outcomes following ta-IPAA, and extract conclusion regarding pediatric UC patients. METHODS: PubMed, Cochrane Library databases, Embase, Web of science and Google Scholar databases were searched, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines. The final search was updated in April 2022. Four comparative cohorts (n = 868) and 11 non-comparative case series (n = 241) were included. Six reports included children. Anastomotic leak, complications, operative time, conversion rate, length of stay and functional outcomes were examined. RESULTS: A total of 1103 patients, ranging 9-79 years were included in this review. We found no difference in risk for anastomotic leak (OR 1.36, 95% CI 0.46-4.06), minor and major complications (OR 0.92, 95% CI 0.48-1.76 and OR 0.78 95% CI 0.36-1.69, respectively) comparing ta-IPAA to transabdominal IPAA. Short- and long-term follow-up showed satisfying functional outcomes and quality of life. CONCLUSIONS: Our review suggests that ta-IPAA is not inferior to transabdominal IPAA. Implementation of this method in children is technically feasible due to familiarity with the dissection plane. Long-term functional outcomes and quality of life are paramount in the pediatric population and should be particularly investigated. Multicenter prospective studies are required to investigate pediatric UC patients undergoing ta-IPAA.


Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Proctocolectomía Restauradora , Adulto , Humanos , Niño , Adolescente , Proctocolectomía Restauradora/métodos , Colitis Ulcerosa/cirugía , Fuga Anastomótica/epidemiología , Calidad de Vida , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Anastomosis Quirúrgica/métodos , Estudios Multicéntricos como Asunto
8.
Pediatr Surg Int ; 38(12): 1737-1743, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36114865

RESUMEN

PURPOSE: Intestinal dysmotility (ID) problems are common in patients with pediatric-onset intestinal failure (IF) and short bowel syndrome (SBS), leading to significant morbidity and delays in the advancement of enteral nutrition (EN). We aimed to investigate the clinical features and complications of ID in children with IF and SBS. METHODS: Retrospective chart review of all children with IF and/or SBS who required parenteral nutrition (PN) > 6 weeks or small-intestinal resection ≥ 50%. Patients were divided into SBS and non-SBS groups. SBS group was divided into two subgroups: with and without ID. Patients with ID were identified (clinically, radiologically and functionally) and analyzed with regard to demographics, intestinal anatomy, complications and outcomes (short and long term). RESULTS: A total of 42 children with IF were treated in our institution during 2003-2022. In non-SBS group (n = 10), ID was the most common cause of IF (80%). SBS-group included 32 children; 18 children (56%) developed ID. The clinical profile of SBS-ID patients (vs SBS) was: female gender (56%), remaining small bowel length ≤ 55 cm, estimated residual small bowel ≤ 28% (p = 0.045) and absence of ICV (56%). Common symptoms of the SBS-ID group were: food intolerance (61%), abdominal distension (50%), vomiting (44%), malabsorption and severe constipation. Complications included FTT (67%) (p = 0.003), bacterial overgrowth with subsequent bloodstream infection (33%) (p = 0.75), and lactic acidosis (11%). Lengthening procedure (STEP) was performed in 11 SBS-ID patients (61%) (p = 0.002). In all patients, STEP operation "rescued" their dysfunctional intestine. Eight of these patients (73%) were weaned from TPN. Survival rate was 100%; however, one SBS-ID patient is a candidate for combined intestinal and liver transplantation. CONCLUSIONS: ID is the most common complication of SBS and is the most common cause of IF in non-SBS patients. ID has a high morbidity rate and various clinical manifestations. Successful treatment of these infants may be achieved with the use of tapering enteroplasty.


Asunto(s)
Insuficiencia Intestinal , Trasplante de Hígado , Síndrome del Intestino Corto , Lactante , Niño , Humanos , Femenino , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del Tratamiento , Síndrome del Intestino Corto/cirugía , Trasplante de Hígado/efectos adversos
9.
Am J Physiol Gastrointest Liver Physiol ; 320(3): G283-G294, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33325807

RESUMEN

This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 wk after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (ICC; downregulation of transmembrane member 16A (TMEM16A) and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to a decrease in final body weight, suggesting less effective nutrient absorption. The purpose of this study was to evaluate the mechanisms of intestinal motility in a rat model of short bowel syndrome (SBS). Rats were divided into three groups: Sham rats underwent bowel transection; SBS-NSI rats underwent a 75% bowel resection and presented with normal intestinal size (NSI) at euthanasia and hypermotility patterns; SBS-DYS showed dysmotile (DYS) enlarged intestine and inhibited motility patterns. Animals were euthanized after 2 wk. Illumina's digital gene expression (DGE) analysis was used to determine the intestinal motility-related gene expression profiling in mucosal samples. Intestinal motility-related and ICC genes and protein expression in intestinal muscle layer were determined using real-time PCR, Western blotting, and immunohistochemistry. Gastrointestinal tract motility was studied by microcomputer tomography. From 10 Ca2+ signaling pathway-related genes, six genes in jejunum and seven genes in ileum were downregulated in SBS vs. Sham animals. Downregulation of TMEM16A mRNA and protein was confirmed by real-time PCR. Rapid intestinal transit time in SBS-NSI rats correlated with a mild decrease in TMEM16A, c-kit, and vimentin mRNA and protein expression (vs/. Sham animals). SBS-DYS rats demonstrated enlarged intestinal loops and delayed small intestinal emptying (on imaging studies) that were correlated with marked downregulation in TMEM16A, c-kit, vimentin, and ghrelin mRNA and protein levels compared with the other two groups. In conclusion, 2 wk following massive bowel resection in rats, impaired intestinal motility was associated with decreased vimentin and ghrelin gene and protein levels as well as loss of ICC (c-kit and TMEM16A).NEW & NOTEWORTHY This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 weeks after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (downregulation of TMEM 16A, and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to decrease in final body weight, suggesting less effective nutrient absorption.


Asunto(s)
Colectomía/efectos adversos , Motilidad Gastrointestinal , Ghrelina/metabolismo , Células Intersticiales de Cajal/metabolismo , Complicaciones Posoperatorias/metabolismo , Síndrome del Intestino Corto/metabolismo , Vimentina/metabolismo , Animales , Anoctamina-1/genética , Anoctamina-1/metabolismo , Ghrelina/genética , Células Intersticiales de Cajal/patología , Masculino , Complicaciones Posoperatorias/patología , Ratas , Ratas Sprague-Dawley , Síndrome del Intestino Corto/etiología , Síndrome del Intestino Corto/patología , Transcriptoma , Vimentina/genética
10.
J Pediatr Gastroenterol Nutr ; 72(1): 49-55, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-32740515

RESUMEN

OBJECTIVES: The aim of this study was to examine the effect of massive small bowel resection on proinflammatory cytokine intestinal expression and the effect of anti-TNF-α antibodies (ATA) on intestinal inflammation, epithelial cell turnover, and intestinal adaptation after bowel resection in rats. METHODS: Male Sprague-Dawley rats were divided into 4 experimental groups: Sham-rats underwent bowel transection; Sham-ATA rats underwent bowel transection and were treated with ATA; SBS-animals underwent 75% bowel resection; and SBS-ATA rats underwent bowel resection and were treated with ATA similarly to Group B. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined at sacrifice. TNF-α and apoptosis-related gene and protein levels were determined by Illumina's Digital Gene Expression (DGE) analysis, Real Time PCR, Western blotting, and immunohistochemistry. RESULTS: From 25 genes related to TNF-α signalling that were investigated, 8 genes in the jejunum and 10 genes in the ileum were found to be up-regulated in resected versus sham animals. SBS rats demonstrated a significant increase in tissue and plasma TNF-α, IL-6 levels, intestinal mucosal TNF-α related gene expression, and microscopic parameters of inflammation. Treatment of resected animals with ATA resulted in a significant decrease in TNF-α levels, intestinal mucosal TNF-α-related gene expression, decreased number of intraepithelial lymphocytes and macrophages, and lower apoptotic index compared with SBS animals. CONCLUSIONS: In a rat model of SBS, ATA decreased plasma and tissue TNF-α levels, diminished mucosal inflammation, and inhibited cell apoptosis. Anti-apoptotic effects of ATA appear to be associated with an inhibited extrinsic apoptotic pathway.


Asunto(s)
Síndrome del Intestino Corto , Animales , Apoptosis , Proliferación Celular , Modelos Animales de Enfermedad , Enterocitos , Mucosa Intestinal , Intestino Delgado/cirugía , Masculino , Ratas , Ratas Sprague-Dawley , Síndrome del Intestino Corto/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral
11.
Pediatr Surg Int ; 37(3): 369-376, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33566162

RESUMEN

PURPOSE: We investigate the mechanism of intestinal cell apoptosis and its relation to the time of reperfusion in a rat model of intestinal ischemia-reperfusion (IR). METHODS: Rats were divided into 4 groups: Sham-24 and Sham-48 rats underwent laparotomy without an intentional ischemic intervention and were sacrificed 24 or 48 h hours later; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 20 min followed by 24 or 48 h of reperfusion, respectively. Park's injury score, cell proliferation and apoptosis were determined at sacrifice. Proliferation and apoptosis-related gene and protein expression were determined using Real-Time PCR, Western Blot and Immunohistochemistry. RESULTS: IR-24 rats demonstrated a strong increase in cell apoptosis along with an elevated Bax and decreased Bcl-2 expression and a decrease in cell proliferation (vs Sham-24). IR-48 group showed an increase in cell proliferation and a decrease in cell apoptosis compared to IR-24 animals. IR-48 rats demonstrated an increase in apoptotic rate that was accompanied by greater TNF-α mRNA, Fas mRNA and FasL mRNA compared to Sham-48 animals. CONCLUSION: While cell apoptosis in IR-24 rats is regulated mainly by intrinsic apoptotic pathway, 48 h followed ischemia extrinsic apoptotic pathway is responsible for pro-apoptotic effects of IR injury.


Asunto(s)
Apoptosis/efectos de los fármacos , Daño por Reperfusión/metabolismo , Animales , Western Blotting , Proliferación Celular , Mucosa Intestinal/metabolismo , Intestinos/fisiopatología , Ratas , Ratas Sprague-Dawley , Transducción de Señal
12.
Pediatr Surg Int ; 35(2): 255-261, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30386903

RESUMEN

PURPOSE: One of the major regulators of gastrointestinal tract development is the hedgehog signaling pathway. The purpose of this study was to evaluate the role of sonic hedgehog (SHh) signaling 24 and 48 h following intestinal ischemia-reperfusion (IR) in a rat. MATERIALS AND METHODS: Male rats were divided into four experimental groups: (1) Sham-24 h rats underwent laparotomy and were sacrificed after 24 h, (2) Sham-48h rats underwent laparotomy and were sacrificed after 48 h, (3) IR-24h rats underwent occlusion of both superior mesenteric artery and portal vein for 20 min followed by 24 h of reperfusion, and (4) IR-48 h rats underwent ischemia for 20 min followed by 48 h of reperfusion. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined by immunohistochemistry 24 and 48 h following IR. SHh-related genes and protein expression were determined using real-time PCR, Western blot and immunohistochemistry. RESULTS: IR-24 rats demonstrated a significant decrease in Shh, Ihh, GIL and Ptch2 mRNA in jejunum and ileum compared to Sham-24 animals that was accompanied by a significant decrease in the number of SHH-positive cells (Immunohistochemistry) in jejunum (2.5-fold decrease) and ileum (37%). After 48 h, IR rats demonstrated a significant increase in Dhh, Ihh, Gil and PTCH2 mRNA in jejunum as well as in Dhh, Ihh, SMO, GIL, PTCH2 mRNA in ileum compared to IR-24 animals that was coincided with increased number of SHH-positive cells in jejunum (2.6-fold increase) and ileum (1.4-fold increase). CONCLUSIONS: 24 h following intestinal IR, inhibited cell turnover was associated with inhibited SHh signaling pathway. Signs of intestinal recovery appeared 48 h after IR and were correlated with increase in SHh signaling pathway activity.


Asunto(s)
Proteínas Hedgehog/metabolismo , Homeostasis , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Enterocitos/metabolismo , Proteínas Hedgehog/genética , Íleon/irrigación sanguínea , Yeyuno/irrigación sanguínea , Masculino , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión , Transducción de Señal
13.
Pediatr Surg Int ; 35(1): 137-143, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30386894

RESUMEN

BACKGROUND: Exposure to ionizing radiation results in cytotoxic and genotoxic effects caused mainly by the oxidative damage. In the present study, we investigated the radioprotective effect of novel antioxidant cocktail on germ cell apoptosis and spermatogenesis in rats subjected to whole body radiation (WBIR). METHODS: Adult male rats weighing 250-270 g were divided into four groups, eight rats each. Group 1 served as untreated control, group 2 received an IP single dose of antioxidant cocktail (1 ml). Group 3 was exposed to a WBIR (6 Gy). Group 4 received antioxidant cocktail before WBIR. Rats from each group were killed after 48 h. MDA levels were measured in serum (TBARS assay). Johnsen's criteria and the number of germinal cell layers were used to categorize spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Statistical analysis was performed using one-way ANOVA test. RESULTS: WBIR resulted in histological testicular damage (decrease in Johnsen's criteria, p < 0.05) that was accompanied by a significant increase in germ cell apoptosis, expressed as the number of apoptotic cells per 100 tubules (AI-1 apoptotic index) and the number of positive tubules per 100 tubules (AI-2 apoptotic index). Treatment with antioxidant cocktail resulted in a significant decrease in germ cell apoptosis (33% decrease in AI-1, p < 0.05 and 34% decrease in AI-2, p < 0.05) that was accompanied by an improved spermatogenesis (increase in Johnsen's criteria, p < 0.05). CONCLUSIONS: In a rat model of WBIR, antioxidant treatment ameliorates oxidative stress-induced testicular damage, decreases germ cell apoptosis and improves spermatogenesis.


Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Células Germinativas/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Animales , Células Germinativas/patología , Células Germinativas/efectos de la radiación , Masculino , Traumatismos Experimentales por Radiación , Radiación Ionizante , Ratas , Ratas Sprague-Dawley , Espermatogénesis/efectos de la radiación , Testículo/efectos de los fármacos , Testículo/patología , Testículo/efectos de la radiación
14.
J Am Coll Nutr ; 37(5): 406-414, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29533141

RESUMEN

BACKGROUND/AIMS: Several studies have demonstrated the antimicrobial, antihelminthic, and antioxidant potential of the active ingredients of pomegranate (PMG) extracts, suggesting their preventive and curative role in several gastrointestinal disorders. In the present study, the authors evaluated the effects of oral PMG supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis during methotrexate (MTX)-induced intestinal damage in a rat. METHODS: Male rats were divided into 4 experimental groups: control rats; CONTR-PMG rats were treated with oral PMG given by gavage once a day 72 hours before and 72 hours following vehicle injection; MTX rats were treated with single dose of methotrexate; and MTX-PMG rats were treated with oral PMG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 72 hours following MTX injection. Western blotting was used to determine phosphorylated extracellular signal-regulated kinase (p-ERK) and caspase 3 protein levels. RESULTS: MTX-PMG rats demonstrated greater jejunal and ileal bowel and mucosal weights, greater jejunal and ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared with MTX animals. A significant decrease in enterocyte apoptosis in ileum of MTX-PMG rats (vs MTX) was associated with a decrease in caspase 3 protein expression as well as increased cell proliferation, which was correlated with elevated p-ERK protein levels. CONCLUSIONS: Treatment with oral PMG prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.


Asunto(s)
Antioxidantes/farmacología , Mucosa Intestinal/efectos de los fármacos , Lythraceae/química , Metotrexato/efectos adversos , Preparaciones de Plantas/farmacología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Jugos de Frutas y Vegetales , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Masculino , Mucositis/patología , Ratas , Ratas Sprague-Dawley
15.
Am J Physiol Gastrointest Liver Physiol ; 313(3): G247-G255, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28619728

RESUMEN

Notch signaling is thought to act to drive cell versification in the lining of the small intestine. The purpose of the present study was to evaluate the role of the Notch signaling pathway in stem cell differentiation in the late stages of intestinal adaptation after massive small bowel resection in a rat. Male Sprague-Dawley rats were randomly assigned to one of two experimental groups of eight rats each: Sham rats underwent bowel transection and reanastomosis, while SBS rats underwent 75% small bowel resection. Rats were euthanized on day 14 Illumina's Digital Gene Expression (DGE) analysis was used to determine Notch signaling gene expression profiling. Notch-related gene and protein expression was determined using real-time PCR, Western blot analysis, and immunohistochemistry. From seven investigated Notch-related (by DGE analysis) genes, six genes were upregulated in SBS vs. control animals with a relative change in gene expression level of 20% or more. A significant upregulation of Notch signaling-related genes in resected animals was accompanied by a significant increase in Notch-1 protein levels (Western blot analysis) and a significant increase in the number of Notch1 and Hes1 (target gene)-positive cells (immunohistochemistry) compared with sham animals. Evaluation of cell differentiation has shown a strong increase in total number of absorptive cells (unchanged secretory cells) compared with control rats. In conclusion, 2 wk after bowel resection in rats, stimulated Notch signaling directs the crypt cell population toward absorptive progenitors.NEW & NOTEWORTHY This study provides novel insight into the mechanisms of cell proliferation following massive small bowel resection. We show that 2 wk after bowel resection in rats, enhanced stem cell activity was associated with stimulated Notch signaling pathway. We demonstrate that activated Notch signaling cascade directs the crypt cell population toward absorptive progenitors.


Asunto(s)
Diferenciación Celular/fisiología , Intestino Delgado/cirugía , Receptores Notch/metabolismo , Transducción de Señal/fisiología , Células Madre/fisiología , Animales , Peso Corporal , Proliferación Celular , Enterocitos/fisiología , Regulación de la Expresión Génica , Intestino Delgado/metabolismo , Intestino Delgado/patología , Masculino , Análisis por Matrices de Proteínas , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Notch/genética
16.
Surg Endosc ; 30(10): 4416-24, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26895894

RESUMEN

BACKGROUND: Bacterial overgrowth is common complication of short bowel syndrome (SBS) and is a result of an impaired gut barrier function. Toll-like receptor 4 (TLR4) is crucial in maintaining intestinal epithelial homeostasis, participates in a vigorous signaling process and heightens inflammatory cytokine output. The objective of this study was to determine the effects of bowel resection on TLR4 signaling in intestinal mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to one of the two experimental groups of eight rats each: Sham rats underwent bowel transection and re-anastomosis and SBS rats underwent 75 % small bowel resection. Rats were killed on day 14. Bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood and peripheral blood was determined at the kill. The expression of TLR4, MyD88 and TRAF6 in the intestinal mucosa was determined using real-time PCR, Western blot and immunohistochemistry. RESULTS: SBS rats demonstrated a 100 % BT to lymph nodes and to liver (Level I), 80 % translocation to portal blood (Level II) and 60 % translocation to peripheral blood (Level III) at day 7 as well as a 100 % BT to lymph nodes and liver, and 40 % translocation to peripheral blood at day 14. Microarray expression profiling demonstrated that most of the TLR signaling-related genes were up-regulated in resected rats compared to control animals. SBS rats showed a significant increase in TLR4 and TRAF6 mRNA in jejunum and ileum, TLR4 and MyD88 protein expression in jejunum and ileum, and a significant increase in the number of TLR4 and TRAF6 positive cells (immunohistochemistry) compared to sham animals. CONCLUSIONS: In a rat model of SBS, elevated intestinal BT is associated with a stimulated TLR4 signaling.


Asunto(s)
Traslocación Bacteriana , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/cirugía , Yeyuno/metabolismo , Síndrome del Intestino Corto/genética , Receptor Toll-Like 4/genética , Animales , Western Blotting , Proliferación Celular , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Modelos Animales de Enfermedad , Inmunohistoquímica , Mucosa Intestinal/patología , Masculino , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Síndrome del Intestino Corto/etiología , Síndrome del Intestino Corto/metabolismo , Síndrome del Intestino Corto/patología , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/metabolismo
18.
Isr Med Assoc J ; 18(11): 673-676, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28466617

RESUMEN

BACKGROUND: The traditional surgical approach to the excision of persistent urachal remnants is a lower midline laparotomy or semicircular infraumbilical incision. OBJECTIVES: To report our experience with laparoscopic/open urachus excision as a minimally invasive diagnostic and surgical technique. METHODS: This was a retrospective study involving patients who were diagnosed with persistent urachus and underwent laparoscopic/open excision. The morbidity, recovery, and outcomes of surgery were reviewed. RESULTS: Eight patients (males:females 6:2) with an age range of 1 month to 17 years underwent laparoscopic or open excision (six and two patients respectively). All patients presented with discharge from the umbilicus. Although three patients had no sonographic evidence of a patent urachus, diagnostic laparoscopy detected a patent urachus that was excised laparoscopically. The operative time of laparoscopic surgery ranged from 19 to 71 minutes (the last case was combined with bilateral laparoscopic inguinal hernia repair), and the mean duration of hospital stay was 2.0 ± 0.36 days. Pathological examination confirmed a benign urachal remnant in all cases. CONCLUSIONS: Laparoscopy is a useful alternative for the management of persistent or infected urachus, especially when its presence is clinically suspected despite the lack of sonographic evidence. The procedure is associated with low morbidity, although a small risk of bladder injury exists, particularly in cases of severe active inflammation.


Asunto(s)
Laparoscopía/métodos , Uraco/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Tiempo de Internación , Masculino , Tempo Operativo , Estudios Retrospectivos , Resultado del Tratamiento , Uraco/anomalías , Uraco/diagnóstico por imagen
19.
Harefuah ; 154(12): 782-5, 804, 2015 Dec.
Artículo en Hebreo | MEDLINE | ID: mdl-26897781

RESUMEN

Management of children with short bowel syndrome is optimized by interdisciplinary coordination of parenteral and enteral nutrition support, medical management of associated complications, surgical lengthening procedures, and intestinal transplantation. Pediatric Intestinal Failure Centers were established in 14 pediatric hospitals throughout the United States and Canada and the Pediatric Intestinal Failure Consortium has been developed and is implementing prospective, multi-institutional studies to better define the specific aspects of intestinal failure management that optimize long-term outcomes. The published data from these studies suggest that intestinal failure in pediatric patients is quite treatable and provides further evidence that all infants at risk for intestinal failure should be treated aggressively and referred early to a dedicated intestinal rehabilitation center. Improved communication and integration with the transplant service have resulted in earlier assessment, decreased rates of transplantation, and decreased mortality from liver failure. The data presented demonstrates that a newly established intestinal failure program can achieve excellent survival in a cohort of chronically ill and complex pediatric cases that have historically been associated with substantial mortality.


Asunto(s)
Nutrición Enteral/métodos , Nutrición Parenteral/métodos , Síndrome del Intestino Corto/rehabilitación , Niño , Humanos , Lactante , Comunicación Interdisciplinaria , Intestinos/trasplante , Síndrome del Intestino Corto/terapia
20.
Harefuah ; 154(12): 774-7, 805, 804, 2015 Dec.
Artículo en Hebreo | MEDLINE | ID: mdl-26897779

RESUMEN

INTRODUCTION: Laparoscopic appendectomy (LA) is widely accepted for simple appendicitis but it is still debatable in complicated cases (gangrenous or perforated appendicitis). AIM: The purpose of the present study was to evaluate the outcomes of LA versus open appendectomy (OA) in uncomplicated and complicated appendicitis in children. METHODS: A retrospective analysis of the clinical data of children (< 18 years old) who underwent LA and CA from 2008 to 2011 was performed. The incidental appendectomies were excluded. The patients were divided into four groups according to the severity of the disease (uncomplicated vs complicated) and by the surgical approach (LA vs OA). Data were compared with regard to demographic features, pre-operative, intra-operative and post-operative findings. MAIN RESULTS: A total of 335 children underwent urgent appendectomy during this period. The overall rate of perforated appendicitis was 26.9%; 143 patients (42.7%) underwent LA and 192 patients (57.3%) underwent CA. Operative times and complication rates did not differ significantly between LA and OA in either complicated to uncomplicated appendicitis; LOS was shorter in the uncomplicated group (2.14 ± 0.17 vs 3.15 ± 0.14, p < 0.01). Two patients from the uncomplicated group underwent conversions form LA to OA (conversion rate of 1.36%) because of intraoperative bleeding, and one patient in the OA-complicated group had a cecal injury. There were no mortalities in this group. CONCLUSIONS: Laparoscopic appendectomy for complicated appendicitis in children is feasible and safe, does not harbor any risks in comparison to the open traditional procedure, and allows the benefits of better view, flexible angle of approach and cosmesis.


Asunto(s)
Apendicectomía/métodos , Apendicitis/cirugía , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Apendicitis/fisiopatología , Niño , Femenino , Humanos , Tiempo de Internación , Masculino , Tempo Operativo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
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