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1.
Children (Basel) ; 11(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38671628

RESUMO

INTRODUCTION: In children, the association of ipsilateral pyeloureteral junction obstruction (PUJO) and ureterovesical junction obstruction (UVJO) is a rare malformation with a non-standardized treatment. We report a case of PUJO and UVJO treated by a combined minimally invasive surgical treatment to resolve the double urinary obstruction. The current literature was also reviewed. CASE REPORT AND REVIEW: A two-month-old boy, without antenatal and postnatal signs of urinary tract anomalies, was hospitalized presenting right hydronephrosis, perirenal fluid effusion, and ascites. An acute pelvic rupture was suspected, and a retrograde pyelogram was performed, showing a primary obstructive megaureter (POM) associated with a corkscrew pyeloureteral junction. The impossibility to place a double J catheter through the pyeloureteral junction led us to achieve percutaneous nephrostomy and an abdominal drain placement. Three months later, the patient underwent a combined high-pressure balloon ureterovesical junction dilation and retroperitoneoscopic Anderson Hynes one-trocar-assisted pyeloplasty (OTAP). The literature search identified 110 children experiencing double urinary tract obstruction. All authors agreed on the difficulty to diagnose both obstructions preoperatively, but there is still no consensus on which obstruction should be relieved earlier, because the alteration in urinary vascularity during a double surgery could damage the ureter. CONCLUSIONS: The simultaneous occurrence of UPJO and UVJO is rare, with a challenging diagnosis. Prompt identification and timely surgical intervention are crucial to mitigate the risk of renal function loss attributable to obstruction and infection. Drawing from our expertise and the analysis of the existing literature, we propose employing a simultaneous double minimally invasive strategy in order to optimize the preservation of ureteral vascularity. This approach entails performing a minimally invasive pyeloplasty for the PUJ and utilizing high-pressure balloon dilatation for the UVJ.

4.
J Pediatr Urol ; 20(2): 283-291, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38000950

RESUMO

INTRODUCTION: Traditionally, open ureteral reimplantation (OUR) has been the standard treatment for primary vesicoureteral reflux (VUR) requiring reimplantation. Robotic-assisted laparoscopic ureteral reimplantation (RALUR) is gaining popularity and high success rates have been reported. OBJECTIVE: In this multi-institutional study, we aimed to compare the perioperative and postoperative outcomes of OUR and RALUR for high-grade (IV + V) VUR in children. STUDY DESIGN: A retrospective evaluation was performed collecting data from 135 children (0-18 years) who underwent high grade VUR surgical correction at nine European institutions between 01/01/2009 and 01/12/2020, involving either open or robotic approaches. Institutional review board approval was obtained. Patients with lower grades of VUR (≤III), previous history of open or endoscopic ureteral surgery, neurogenic bladder, or refluxing megaureter in need of ureteral tapering were excluded. Pre-, peri- and post-operative data were statistically compared. RESULTS: Overall, 135 children who underwent either OUR (n = 68), or RALUR (n = 67) were included, and their clinic and demographic features were collected. The mean age of the open group was 11 months (interquartile range [IQR] 9.9-16.6 months), in the RALUR group it was 59 months (IQR 29-78mo) (p < 0.01); the open cohort had a weight of 11 kg (IQR 9.9-16.6 kg) while the RALUR group had 19 kg (IQR 13-25 kg) (p < 0.01). No significant differences were found for intraoperative (1.5 % vs 7.5 %, p = 0.09) or for postoperative complication rates (7.4 % vs 9 %, p = 0.15). Favorable outcomes were reported in the RALUR group: shorter time to stooling (1 vs 2 days), fewer indwelling urethral catheter days (1 vs 5 days), perioperative drain insertion time (1 vs 5 days) and a shorter length of hospital stay (2 vs 5 days) (p < 0.01). The success rate was 94.0 % and 98.5 % in the open and RALUR groups, respectively. The long-term clinical success rates from both groups was comparable:42 vs 23 months for open and RALUR, respectively. DISCUSSION: This study reported a large multicentric experience focusing on high grade VUR. Furthermore, this study compares favorably to OUR in a safety analysis. There was also a trend towards higher success rates with RALUR utilizing an extravesical approach which has not been previously reported. CONCLUSION: RALUR is an efficacious and safe platform to use during ureteral reimplantation for high grade VUR. The overall peri-operative and post-operative complication rates are at least equivalent to OUR, but it is associated with a faster functional recovery and time to discharge. Medium to long term success rates are also equivalent to OUR.

5.
J Pediatr Urol ; 20(1): 95-101, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37845102

RESUMO

Undescended testis (UDT, cryptorchidism) is the most common congenital anomaly of the genital tract. Despite its high incidence, the management of UDT varies between specialties (urology, pediatric surgery, pediatric urology, pediatric endocrinology). Therefore, as the European Association of Urology - Young Academic Urologists Pediatric Urology Working Group, we requested experts around the world to express their own personal approaches against various case scenarios of UDT in order to explore their individual reasoning. We intended to broaden the perspectives of our colleagues who deal with the treatment of this frequent genital malformation.


Assuntos
Criptorquidismo , Urologia , Masculino , Humanos , Criança , Criptorquidismo/diagnóstico , Criptorquidismo/cirurgia , Criptorquidismo/epidemiologia , Testículo , Urologistas , Incidência
6.
Front Surg ; 10: 1322085, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38145215

RESUMO

Objective: The purpose of this study was to determine whether the use of a humanoid robot (Estrabot) could reduce preoperative anxiety levels in children. Methods: An experimental study was conducted at Azienda Ospedaliero Universitaria delle Marche Hospital, involving the Pediatric Surgery ward and the Operating Room (OR). Patients aged between 2 and 14 years who underwent minor surgery were included. The Instruments used were the Children's Emotional Manifestation Scale to evaluate anxiety levels, and Estrabot, a humanoid robot that interacts with people. Medical records between April and May 2023 were analyzed and the data was anonymous. The level of anxiety is extrapolated in Pediatric Surgery during the administration of oral pre-medication, and in the Operating Room, during the induction of anesthesia. Patients were divided into an intervention group treated with Estrabot, and a control group without a robot. Results: The population consists of 60 patients (86.7% male) with a median (IQR) age of 6 (4-8) years. The median (IQR) anxiety score during premedication was 7 (5-11), while the median (IQR) anxiety score during anesthesia was 6 (5-10). A significantly lower level of anxiety was reported in the Estrabot group. Patients in the Estrabot group had significantly lower anxiety levels in different age groups. Conclusion: A humanoid robot can reduce preoperative anxiety levels in children during premedication and the induction of anesthesia.

7.
Children (Basel) ; 10(9)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37761409

RESUMO

BACKGROUND: Robot-assisted pyeloplasty is widely used in pediatric surgery because of its well-known advantages over open or laparoscopic surgery. The aim is to explore our experience and evaluate the achievements we have made. METHODS: We evaluated patients undergoing robotic pyeloplasty from January 2016 to November 2021, including those who presented with a ureteropelvic junction obstruction associated with other anomalies of the kidney. The parameters examined were: age, weight, associated renal malformations, conversion rate, operative time, and intra- and postoperative complications. RESULTS: Of 39 patients, 7 (20%) were included, of whom 5 (71%) were male and 2 (29%) were female. The mean age at surgery was 84 months (range 36-180 months), and the mean weight at surgery was 24.4 kg (range 11-40 kg). In five (71%) patients the ureteropelvic junction obstruction (UPJO) was left-sided and in two (29%) it was right-sided. In four (57%) cases, UPJO was associated with a horseshoe kidney, right-sided in one (25%) patient, and left-sided in the other three (75%). A 180° rotation of the kidney was present in one (14%) patient. Nephrolithiasis was present in two (29%) patients. The mean operative time was 160 min (range 140-240 min). The average bladder catheter dwell time was 1 day (range 2-3 days), while the average abdominal drainage dwell time was 2 days (range 2-4 days). The mean hospitalization time was 4 days (range 3-9 days). On average, after 45 days (range 30-65) the JJ ureteral stent was removed cystoscopically. No intraoperative complications were reported, while one case of persistent macrohematuria with anemia requiring blood transfusion occurred postoperatively. CONCLUSIONS: Ureteropelvic junction obstruction might be associated with other congenital urinary tract anomalies such as a duplicated collecting system, horseshoe kidney, or pelvic kidney. These kinds of malformations can complicate surgery and require more attention and accuracy from the surgeon. Our experience shows that, with regards to the robotic learning curve required for pyeloplasty, the treatment of the ureteropelvic junction in these situations does not present insurmountable difficulties nor is burdened by complications. The application of robot-assisted surgery in pediatric urology makes difficult pyeloplasties easier.

8.
Pediatr Med Chir ; 45(1)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37428106

RESUMO

Urothelial bladder neoplasms (UBN) are uncommon in children and are poorly understood. Their management is contentious, and there are currently no pediatric guidelines available, making it difficult to envision a surgical approach that can be defined as the gold standard for the treatment of these diseases. Pneumovesicoscopy, which has already been used to treat other urological diseases, could be a promising treatment option for selected cases of this group of pathologies. We present our experience with three pediatric UBN cases in which pneumovesicoscopy was used for complete excision of a perimeatal papilloma in two cases and biopsy of a botryoid rhabdomyosarcoma in one. The pneumovesicoscopic approach, in our experience, provided a viable alternative technique for the management of selected cases of UBN.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias da Bexiga Urinária , Humanos , Criança , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Biópsia
9.
Eur Urol Open Sci ; 52: 60-65, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37284042

RESUMO

Background: The term glass ceiling coined by Loden in 1978 is commonly used to describe difficulties faced by minorities and women when trying to move into senior roles. Objective: To analyse trends and patterns for female representation at the European Association of Urology (EAU) and European Society for Paediatric Urology (ESPU) annual general meetings over the past decade. Design setting and participants: We used objective data on female representation in the roles of chairs, moderators, and lecture speakers at the EAU and ESPU meetings from 2012 to 2022. Outcome measurements and statistical analysis: We evaluated gender based representation in paediatric urology sessions at the EAU and ESPU meetings, collecting data on the overall number of sessions, lectures, symposiums, abstract/poster sessions, and courses, and analysed the male/female ratio. Data were derived from printed and digital programmes for the relevant meetings. Results and limitations: During the period from 2012 to 2022, the percentage female representation varied from 0% (2012) to a maximum of 35% (2022) at EUA paediatric urology sessions, and from 13.5% (2014) to a maximum of 32% (2022) at ESPU meetings. Both associations show clear progression towards equality. Conclusions: Female representation at EAU and ESPU meetings has risen over the years, reaching 35% and 32%, respectively, in 2022, which is in line with the number of female members. We hope that this motivates a move towards the equality objectives for 2030. A clear and fundamental societal change is needed, with fair and more consistent institutional policies and framework commitments in the areas of science, medicine, and global health. Gender equality and diversity taskforces are essential to achieve these goals. Patient summary: We analysed the male/female ratio for participants in annual meetings held by the European Association of Urology and the European Society for Paediatric Urology. From a low level in 2012, the ratio increased to over 30% in 2022, in line with the female membership of the societies. Focus on fair and consistent policies is needed to ensure that women are well represented in medicine.

10.
Pediatr Med Chir ; 45(1)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37114377

RESUMO

Laparoscopic Appendectomy (LPSA) is the first choice for appendectomy in pediatric surgery. Trans-Umbilical Laparoscopic Assisted Appendicectomy (TULAA) is another used technique. We compared both these procedures used for the treatment of acute appendicitis. The study was conducted between January 2019 to December 2020. Patients were divided into two groups: LPSA and TULAA groups. The collected data were: operative time, number of conversions, time of canalization and hospital stay. A total of 181 patients were included: 73 were kept in the LPSA and 108 in the TULAA group. Mean operative time was 70.9 minutes (range 45-130 min) for LPS and 56.4 (30-145 min) for TULAA group (p <0.0001). Complications rate showed no statistically significant difference between both the two groups. However, conversions showed a statistically significant difference (p=0.04). Both techniques showed similar results. TULAA technique takes a significantly shorter operating time. The selection between LPSA and TULAA techniques depends on the experience of the surgeon's work and the personal laparoscopic learning curve. In our experience LPSA was a useful technique to improve the laparoscopic skill of the pediatric surgery residents.


Assuntos
Apendicite , Laparoscopia , Humanos , Criança , Apendicectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Apendicite/cirurgia , Laparoscopia/métodos , Tempo de Internação
11.
Diseases ; 11(1)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36810533

RESUMO

Hypertrophic pyloric stenosis is a common cause of vomiting in the first few weeks of life, but in rare cases, it may occur in older subjects with a major risk of delayed diagnosis and complications. We describe the case of a 12-year-and-8-month-old girl who presented to our department for epigastric pain, coffee-ground emesis, and melena, which arose after taking ketoprofen. An abdomen ultrasound showed thickening (1 cm) of the gastric pyloric antrum, while upper-GI endoscopy documented esophagitis and antral gastritis with a non-bleeding pyloric ulcer. During her hospital stay, she had no further episodes of vomiting and was therefore discharged with a diagnosis of "NSAIDs-induced acute upper gastrointestinal tract bleeding". After 14 days, following recurrence of abdominal pain and vomiting, she was hospitalized again. At endoscopy, pyloric sub-stenosis was found, abdominal CT showed thickening of large gastric curvature and pyloric walls, and an Rx barium study documented delayed gastric emptying. On suspicion of idiopathic hypertrophic pyloric stenosis, she underwent Heineke-Mikulicz pyloroplasty with resolution of symptoms and restoration of a regular caliber of the pylorus. Hypertrophic pyloric stenosis, although occurring rarely in older children, should be taken into account in the differential diagnosis of recurrent vomiting at any age.

12.
Children (Basel) ; 9(7)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35884005

RESUMO

Introduction: Robotic surgery has shown explicit benefits and advantages in adults, but it is not yet strongly established in the pediatric population, even though its popularity is increasing, especially in the urologic field. Materials and methods: In this article we present our experience with the Da Vinci System (SI first and XI nowadays) at our pediatric institution in order to analyze our progress over the years. We considered all patients from the start of the robotic surgery program in 2016 until the end of 2021, dividing them into general abdominal surgery and genitourinary surgery. Analyzed data were the patient's demographic, details of surgery, and intra and post-operative complications. Results: The total number of patients (pts) included in this study was 76, of whom 40 (52%) were male and 36 (48%) were female. The mean age at surgery was 90.9 months (range 10-207 months), and the mean weight at surgery was 29.3 kg (range 9.5-68 kg). There were 18 general abdominal robotic surgeries and 58 genitourinary robotic surgeries performed. The most performed surgeries in these two categories were fundoplication for gastro-oesophageal reflux disease (11%) and Anderson-Hynes pyeloureteroplasty. The mean operative time was 224.2 min (range 72-530 min): the mean times in the two groups (general abdominal surgery and genitourinary surgery) were 165 min (range 84-204 min) and 194 min (range 95-360 min), respectively. A total of four (5%) minor complications were reported. The total conversions were two (2.6%) and the mortality rate was 0%. Conclusions: Pediatric robotic surgery is a field of considerable interest and it is rapidly expanding. In our experience, it is evident how the learning curve has increased gradually, but steadily, allowing us to advance from standardized surgery, such as fundoplication and pieloplasty, towards a more technically complex one, achieving the same good results. We believe that robotic surgery is very respectful of tissues and feasible, especially for reconstructive surgery. For these reasons, it could become of common use also in the pediatric population, overcoming impediments such as excessive cost and the lack of pediatric instruments, in order to be able to treat children with a progressively lower age and weight.

13.
Gynecol Endocrinol ; 38(7): 612-614, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35532169

RESUMO

BACKGROUND: The presence of a rare lesion for pediatric population, encountered in twins, as far as we know, is an exceptional event. The event made the management of a pathology, for which there are no guidelines in the pediatric field, even more delicate. CASE REPORT: Two twin sisters came to our attention, a short time after each other, due to the presence of a voluminous abdominal mass. After complete resection, the histological diagnosis was that of a paraovarian cystoadenofibroma. DISCUSSION: In pediatric surgery being minimally invasive is mandatory. However in selected cases the only objective, especially speaking of pediatric patients, ais to be radical and to protect the adnexal structures.


Assuntos
Irmãos , Gêmeos , Adolescente , Criança , Humanos
14.
Children (Basel) ; 9(4)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35455549

RESUMO

Background: Paediatric nephrolithiasis has increased globally, requiring standardized recommendations. This study aims to assess the paediatric urolithiasis care between EAU members along with the statements of three experts in this field. Methods: The results of an electronic survey among EAU members comparing the guideline recommendations to their current practice managing paediatric nephrolithiasis in 74 centres are contrasted with insights from an expert-panel. The survey consisted of 20 questions in four main sections: demographics, instrument availability, surgical preferences and follow-up preferences. Experts were asked to give insights on the same topics. Results: A total of 74 responses were received. Computerised Tomography was predominantly used as the main imaging modality over ultrasound. Lack of gonadal protection during operations was identified as an issue. Adult instruments were used frequently instead of paediatric instruments. Stone and metabolic analysis were performed by 83% and 63% of the respondents respectively. Conclusions: Percutaneous Nephrolithotomy is the recommended standard treatment for stones > 20 mm, 12% of respondents were still performing shockwave lithotripsy despite PNL, mini and micro-PNL being available. Children have a high risk for recurrence yet stone and metabolic analysis was not performed in all patients. Expert recommendations may guide clinicians towards best practice.

15.
Children (Basel) ; 9(3)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35327790

RESUMO

We herein report a case of giant congenital hepatoblastoma in a 3-month-old male treated with neoadjuvant chemotherapy and hepatic resection. After considerable reduction of the tumor with chemotherapy, a right bloodless hemihepatectomy using saline-linked radiofrequency technology (SLRT) and without clamping of the hepatic pedicle was performed. Intraoperative blood loss was minimal, and consequently, no blood transfusions were required. The surgery lasted 140 min, and SLRT was used for a total of 60 min. No complications were observed during or after the surgery. In conclusion, congenital hepatoblastoma is a very rare cancer for which surgery is an essential therapeutic step, and in our presented case, we showed that SLRT allowed for a safe and effective bloodless liver resection.

16.
Pediatr Med Chir ; 43(2)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34148340

RESUMO

Bronchogenic Cysts (BCs) are benign congenital malformations commonly located in the mediastinum. In recent years the development of antenatal diagnosis has changed the BCs management allowing an earlier minimally invasive approach. We report a case of an asymptomatic 8-months-old girl with antenatal diagnosis of subcarinal posterior mediastinal BC. Thoracoscopic excision of the cyst was successfully performed. The management of antenatally diagnosed BCs is discussed. Thoracoscopic treatment of BCs is safe and effective with the advantage of a reduced morbidity compared to thoracotomy.


Assuntos
Cisto Broncogênico , Cisto Mediastínico , Cisto Broncogênico/diagnóstico por imagem , Cisto Broncogênico/cirurgia , Feminino , Humanos , Lactente , Cisto Mediastínico/diagnóstico por imagem , Cisto Mediastínico/cirurgia , Mediastino/diagnóstico por imagem , Mediastino/cirurgia , Gravidez , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Children (Basel) ; 8(4)2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33916416

RESUMO

Introduction: To report our experience in continent urinary diversions, we describe two cases we treated performing detubularized ureterosigmoidostomy. In children, in the case of malformations or neoplastic diseases affecting the bladder, the need for a cystectomy is not so frequent. When cystectomy becomes mandatory, there is a need to create a continent bladder diversion. Mainz pouch II and Cologne pouch are procedures that utilize a detubularized sigma as a reservoir in order to build up a continent neo-bladder. Materials and methods: This is a retrospective study performed at the Pediatric Surgical Unit of the Salesi Children's Hospital. In this work, we reviewed data about two patients who underwent surgery for the creation of a sigmoid neo-bladder by the Mainz pouch II and Cologne pouch techniques. Results: In our experience, we treated a girl who was affected by a bladder's rabdomiosarcoma and a girl born with a bladder exstrophy and treated at birth abroad. In both patients, a complete cystectomy was performed and a continent neo-bladder was created by a detubularized ureterosigmoidostomy. In the first case, we performed the Mainz pouch II technique and in the second, the Cologne pouch technique. Discussion: Different techniques have been developed with the main goal of the creation of an orthotopic neo-bladder, which has to be a low pressure reservoir with a continent sphincteric mechanism. Detubularized ureterosigmoidostomy is a good choice in pediatric patients. Our study, according to other works, shows that these procedure are safe with good long-term outcomes.

18.
Pediatr Surg Int ; 37(3): 333-337, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33555396

RESUMO

AIM OF THE STUDY: Midgut volvulus is a potentially life-threatening condition which is based on intestinal ischemia and reperfusion (I/R) injury. Remote ischemia conditioning (RIC) applied to a limb can protect distant organs such as heart and kidney. The aims of this study were to investigate the effect of RIC on a model of midgut volvulus and to explore its underlying mechanism of action. METHODS: Six-weeks old C57BL/6 mice were studied: (a) sham (n = 4): laparotomy alone. (b) Intestinal I/R injury (n = 5): occlusion of the superior mesenteric artery (SMA) for 45 min followed by reperfusion. (c) Intestinal I/R (as in group above) with RIC immediately after reperfusion (n = 5). RIC consisted of 4 cycles of 5 min hind limb ischemia followed by 5 min reperfusion. 24-h after laparotomy, animals were euthanized, and the small intestine (same distance from cecum) was harvested. The intestine was examined for inflammatory cytokines (TNF-α and IL-6), epithelial proliferation marker Ki67 and stem cell marker Lgr5 expression. MAIN RESULTS: Compared to sham, the small intestine of IR mice had more intestinal damage, increased expression of inflammatory cytokines, decreased intestinal proliferation and stem cell activity. RIC significantly counteracted all these changes. CONCLUSIONS: Remote ischemia conditioning avoids intestinal damage due to I/R injury. This beneficial effect is associated with decreased intestinal inflammation and enhanced intestinal regeneration. This study implicates that RIC is a novel non-invasive intervention to reduce the intestinal damage occurring in midgut volvulus.


Assuntos
Intestino Delgado/patologia , Traumatismo por Reperfusão/metabolismo , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Extremidades , Inflamação/metabolismo , Intestino Delgado/metabolismo , Intestinos/irrigação sanguínea , Isquemia , Rim , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração , Reperfusão
19.
Pediatr Surg Int ; 37(3): 325-332, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33547933

RESUMO

PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease that can cause damage to remote organs. Previous studies have shown that inflammatory and oxidative injury occur in the liver during NEC. Mitochondrial DNA (mtDNA) plays an important role in hepatic injuries of many other diseases. We aimed to investigate the mechanism of mitochondrial dysfunction in hepatic oxidative injury during NEC. METHODS: NEC was induced in C57BL/6 mice (approval: 44032) by hypoxia, gavage feeding with hyperosmolar formula, and lipopolysaccharide administration from postnatal days 5 to 9 (n = 15). Two additional groups with hypoxia only (n = 10) and hypoxia and hyperosmolar formula (n = 13) were also examined. Breastfed pups were used as control (n = 15). Liver was harvested on postnatal day 9. Gene expressions of mtDNA markers cytochrome c oxidase subunit 3 (COX3), cytochrome b (CYTB) and NADH-ubiquinone oxidoreductase chain 1 (ND1) were measured by real-time qPCR. Mitochondrial morphology marker HSP60 and oxidative stress marker NRF2 were detected by immunofluorescence staining and compared between NEC and control. Data were presented as mean ± SD and compared using Student's t test; p < 0.05 was considered significant. RESULTS: Gene expression of mtDNA markers (COX3, CYTB, and ND1) were significantly decreased in the liver of NEC mice relative to control, hypoxia alone, and hypoxia with hyperosmolar formula. Immunofluorescence showed depletion of HSP60 indicating decreased mitochondria in NEC liver relative to control. Furthermore, a higher protein expression of NRF2 was observed indicating higher oxidative stress in NEC liver relative to control. CONCLUSIONS: Intestinal injury in experimental NEC leads to a systemic inflammatory response affecting the liver. Hepatic oxidative injury in NEC is characterized by decreased mitochondria and mtDNA depletion. This study provides insight into the mechanism of liver injury in NEC.


Assuntos
Enterocolite Necrosante/patologia , Fígado/metabolismo , Mitocôndrias/metabolismo , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Nutrição Enteral/efeitos adversos , Expressão Gênica , Humanos , Hipóxia , Recém-Nascido , Doenças do Recém-Nascido , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
20.
Pediatr Surg Int ; 36(3): 271-277, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31950358

RESUMO

PURPOSE: Activation of calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been shown to increase intestinal injury and inhibit epithelial cell proliferation in dextran sulfate sodium (DSS)-induced colitis mice. However, the role of CaMKIV in necrotizing enterocolitis (NEC) is unknown. We aimed to study the expression and activation of CaMKIV in experimental NEC. METHODS: Following ethical approval, NEC (n = 10) was induced in C57BL/6 mouse pups by hypoxia, gavage hyperosmolar formula feeding and lipopolysaccharide from postnatal days P5 to 9. Breastfed pups served as control (n = 10). Mouse pups were sacrificed on P9 and the terminal ileum was harvested. Gene NEC injury was scored blindly by three independent investigators. CaMKIV, CREM and IL17 gene expression, and CaMKIV and pCaMKIV protein expression were assessed. The data were compared using Mann-Whitney U test. P < 0.05 was considered significant. RESULTS: Intestinal injury was induced in the NEC mice and confirmed by histological scoring and inflammatory cytokine IL6. CaMKIV and its downstream target genes of CREM and IL17 were significantly elevated in NEC mice relative to control. Similarly, phosphorylated-CaMKIV (pCaMKIV), the active form of CaMKIV, was more notably expressed in the NEC ileal tissue relative to control ileal tissue. Elevated pCaMKIV protein expression was also confirmed by western blot. CONCLUSION: CaMKIV expression and activation are upregulated in experimental NEC suggesting a potential contributing factor in the pathogenesis of NEC.


Assuntos
Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/genética , Enterocolite Necrosante/metabolismo , Regulação da Expressão Gênica , Íleo/metabolismo , RNA/genética , Regulação para Cima , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/biossíntese , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Enterocolite Necrosante/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
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