Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Analysis of pediatric sternal fractures using the Kid's Inpatient Database (KID).

PURPOSE: This study aims to determine if sternal fracture is a predictor of discharge requiring additional care and mortality. METHODS: Blunt pediatric trauma admissions (<18 years) in the Kid's Inpatient Database (2016) were included in analysis. Weighted incidence of sternal fracture was calculated and adjusted for using survey weight, sampling clusters, and stratum. Regression analysis was used to identify factors associated with poor outcomes. RESULTS: Annual incidence of sternal fracture in the pediatric blunt trauma population was 0.43 per 100,000. Of 50,076 patients identified, 236 had sternal fractures. The sternal fracture patients were older (median 16 vs 10 years, P < 0.001) and motor vehicle accident was more frequently the mechanism of injury (78% vs 24%, P < 0.001). Common injuries associated with sternal fracture included clavicle fracture (43%), abdominal organ injury (28%), spinal fracture (47%), lung injury (65%), and rib fracture (47%).  Sternal fracture patients were more frequently discharged to receive additional care (22% vs 5%, P < 0.001) and to die of their injuries (3.8% vs 0.9%, P < 0.001). When adjusting for other factors associated with poor outcomes, sternal fracture was not an independent predictor of mortality or discharge to care. CONCLUSIONS: Sternal fracture is a severe injury in the pediatric population, but it is not independently associated with need for a higher level of care after discharge or mortality.

Fetal inflammation induces acute immune tolerance in the neonatal rat hippocampus.

BACKGROUND: Infants born preterm due to chorioamnionitis are frequently affected by a fetal inflammatory response syndrome (FIRS) and then by subsequent postnatal infections. FIRS and postnatal systemic inflammatory events independently contribute to poor neurocognitive outcomes of preterm infants. Developmental integrity of the hippocampus is crucial for intact neurocognitive outcomes in preterms and hippocampally dependent behaviors are particularly vulnerable to preterm systemic inflammation. How FIRS modulates the hippocampal immune response to acute postnatal inflammatory events is not well understood. METHODS: Prenatal LPS exposed (FIRS) and control neonatal rats received i.p. LPS or saline at postnatal day (P) 5. On P7, immune response was evaluated in the hippocampus of four treatment groups by measuring gene expression of inflammatory mediators and cytosolic and nuclear NFκB pathway proteins. Microglial activation was determined by CD11b+ and Iba1+ immunohistochemistry (IHC) and inflammatory gene expression of isolated microglia. Astrocyte reactivity was measured using Gfap+ IHC. RESULTS: Postnatal LPS resulted in a robust hippocampal inflammatory response. In contrast, FIRS induced by prenatal LPS attenuated the response to postnatal LPS exposure, evidenced by decreased gene expression of inflammatory mediators, decreased nuclear NFκB p65 protein, and fewer activated CD11b+ and Iba1+ microglia. Isolated microglia demonstrated inflammatory gene upregulation to postnatal LPS without evidence of immune tolerance by prenatal LPS. CONCLUSION: Prenatal LPS exposure induced immune tolerance to subsequent postnatal LPS exposure in the hippocampus. Microglia demonstrate a robust inflammatory response to postnatal LPS, but only a partial immune tolerance response.

Ocular Injury Presenting to a Level-III Pediatric Trauma Center.

The purpose of this study is to describe pediatric ocular injuries presenting to a level-III pediatric trauma center and emergency department. METHODS: We performed a retrospective study and identified children from January 1, 2011, to January 1, 2016. Charts were reviewed for any subject, age from newborn to younger than 18 years, based on International Classification of Diseases, ninth and tenth revision, codes for any ocular injury. Data abstraction included age, sex, means of arrival, eye involved, mechanism of injury, type of ocular injury, imaging studies obtained, procedures performed, location of definitive repair (in the operating room or emergency department), and subspecialty services involved. RESULTS: In the 5-year period, we describe 356 injuries among 278 children. Males had a slightly higher rate of presentation than females (156 and 122, respectively). Forty-three children (15.46%) required repair in the operating room. Dog bites comprised of 7.19% children with outpatient follow-up, one patient (0.36%) eventually developed anophthalmia, and 30 children (10.79%) had long-term ophthalmological sequelae (ie, glaucoma and blindness). CONCLUSIONS: At our institution, a level-III trauma center, we evaluated and managed approximately 1 ocular injury case per week and children required surgical repair in the operating room at a higher rate than higher-level trauma centers. Injuries secondary to dog bites remain a clinically significant etiology.

Standardized irrigation technique reduces intraabdominal abscess after appendectomy.

PURPOSE: The utility of irrigation at the time of appendectomy for acute appendicitis has been debated, with recent studies showing no benefit to irrigation. In our practice, two techniques have been used; one in which irrigation was at the discretion of the surgeon, and one in which irrigation was standardized. The standardized irrigation technique involved large volume (3-12 l) irrigation in small, focused, directed aliquots to achieve optimal dilution. We sought to retrospectively assess whether the standardized large volume irrigation technique was associated with measurably reduced intraabdominal infection. We hypothesized that there would be no difference in intraabdominal infection rate. METHODS: Medical records for cases of appendectomies performed for acute appendicitis, years 2007 through 2017, were reviewed (n = 432). Rate of subsequent abdominal infection was compared between patients who underwent the standardized large volume irrigation technique compared to those who did not using Fisher's exact test; p < 0.05 was considered significant. RESULTS: For patients that underwent the standardized large volume irrigation technique there were no (0/140) subsequent abdominal infections within the study period, compared with a rate of 6.2% (18/292) for all other patients (p value 0.001). Among cases that had a perforated appendix (n = 105), the rates were 0% (0/31) compared to 18.9% (14/74; p value 0.009). CONCLUSIONS: Utilization of a standardized large volume irrigation technique with the objective of serial dilution is associated with a significantly lower rate of subsequent abdominal infection, even among cases with a perforated appendix. Prospective studies are needed to evaluate this technique. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Treatment study.

Combined laparoscopic-fluoroscopic technique for primary gastrojejunostomy button tube placement.

BACKGROUND: Gastrojejunostomy (GJ) tubes are frequently used to provide pediatric enteral nutritional support for pediatric patients. Various placement methods have been described, each with attendant advantages and disadvantages. DESCRIPTION OF THE OPERATIVE TECHNIQUE: We present a technique for primary laparoscopic/fluoroscopic GJ button tube placement designed to avoid delay in placement of the jejunal limb, and difficulties associated with endoscopic-assisted and primary fluoroscopic placement. RESULTS: There were 52 gastrojejunostomy button tubes placed via this technique in patients ranging from 3.8 to 90.3 kg in weight. Three postoperative complications were identified; one bowel perforation on postoperative day two, and two tube dislodgements within 30 days. CONCLUSION: The described technique was uniformly effective and was associated with a low complication rate (5.8%).

Peritoneal dialysis catheter placement, outcomes and complications.

PURPOSE: Peritoneal dialysis (PD) is a commonly used method for renal support in pediatric patients and can be associated with the risk of post-surgical complications. We evaluated method of placement of PD catheters with regard to post-surgical complications. METHODS: PD catheters placed at two institutions between 2005 and 2017 were reviewed. Complication rates were evaluated based on method of placement, delayed usage, omentectomy, and patient age using Fisher's exact test, two-sided, with significance set at 0.05. Factors influencing complication were evaluated with multivariate logistic regression and Kaplan-Meier survival analysis. RESULTS: There were 130 patients with 157 catheters placed, ranging in age from 1 day to 23 years. There was no significant difference in complication rate by method of placement or delayed usage. Infants were significantly more likely to experience leakage (21% vs 8%, p 0.036) and hernias (15% vs 5%, p 0.030). Patients that underwent an omentectomy were less likely to require a catheter replacement (7% vs 27%, p 0.004), and the catheters had a significantly higher survival rate (p 0.009). We found that laparoscopic intervention resulted in catheter salvage. Lateral exit sites may be a risk factor for catheter migration in some patients. CONCLUSIONS: Omentectomy is associated with longer PD catheter survival. Laparoscopic salvage of dysfunctional catheters may be a valuable adjunct in management.

Radial umbilical dermatofasciolysis to invert the skin following umbilical herniorrhaphy.

BACKGROUND: Umbilical hernia is a common congenital anomaly, and can result in the appearance of a protuberant umbilicus. In select cases, inversion of the umbilical skin can be impaired by the presence of thickened dermis or fascial remnants of the umbilical stalk. DESCRIPTION OF OPERATIVE TECHNIQUE: After umbilical herniorrhaphy, the skin is everted over the left index finger and radial partial thickness incisions in the fascia and dermis of the undersurface of the umbilicus. The umbilical skin is then inverted and secured to the fascia. CONCLUSION: This operative technique can allow complete inversion of the umbilical skin creating an aesthetically appealing umbilical hernia repair.

Enteric glial-mediated enhancement of intestinal barrier integrity is compromised by morphine.

BACKGROUND: The opioid epidemic is a growing concern, and emerging evidence suggests that morphine use may be associated with sepsis. Enteric glial cells (EGCs) are the most numerous cell type in the enteric nervous system and regulate gastrointestinal function through the production of trophic factors, including glial-derived neurotrophic factor (GDNF). We sought to determine the effect of morphine on enteric glia and hypothesized that morphine contributes to EGC dysfunction and increased gut permeability. MATERIALS AND METHODS: Rat intestinal epithelial cells (IECs) and EGC lines were purchased from ATCC. Immunocytochemistry was used to evaluate the impact of EGCs on IEC barrier proteins and detect the µ-opioid receptor. Co-culture assays were used to determine the effect of EGCs, GDNF, and morphine on barrier integrity. Quantitative polymerase chain reaction and western blotting were performed to determine the impact of morphine in GDNF production. Transepithelial resistance of IEC-6 cell monolayers was measured in the presence of EGC-conditioned media (EGC-CM) and morphine treated EGC-CM using electrical cell impedance sensing. RESULTS: EGC-CM enhanced tight junction organization in IECs. IEC barrier integrity was enhanced when co-cultured with unstimulated EGCs or with GDNF alone; this barrier protective effect was lost with morphine-treated EGCs. GDNF RNA and protein expression were decreased by morphine treatment. Transepithelial resistance was decreased in IEC confluent monolayers when exposed to morphine-treated EGC-CM compared with control. CONCLUSIONS: Morphine compromises intestinal epithelial cell barrier function through a mechanism which appears to involve GDNF. Further studies are warranted to delineate the role of enteric glial cell function in opioid signaling and sepsis.

An occult ectopic parathyroid adenoma in a pediatric patient: a case report and management algorithm.

BACKGROUND: Hyperparathyroidism (HPT) is a rare disease in the pediatric population, and optimal management may be unclear if it is due to an occult parathyroid adenoma. We present a case report of a pediatric patient with an occult, ectopic, supernumerary, parathyroid adenoma. CASE PRESENTATION: A 13-year-old female who initially presented with anxiety was diagnosed with HPT. Preoperative imaging and bilateral neck exploration with four-gland biopsy were negative for any parathyroid adenoma. Postoperative MRI identified a thymic mass. She subsequently underwent video-assisted thoracoscopic thymectomy with resection of an intrathymic parathyroid adenoma. CONCLUSIONS: The diagnosis of pediatric HPT is increasing. Supernumerary or occult parathyroid adenomas are rare and add complexity to presurgical planning and management. Our case represents the rare occurrence of a pediatric ectopic supernumerary occult parathyroid adenoma treated with a two-stage approach utilizing multiple imaging studies. We provide a review of the pathology and propose an algorithmic approach to manage these complex patients.

Experience with totally laparoscopic distal pancreatectomy with splenic preservation for pediatric trauma--2 techniques.

PURPOSE: Blunt pancreatic traumatic injury in children, although rare, can be managed with a variety of methods from nonoperative, early operative, or delayed operative strategies. In the appropriate setting, early operative intervention has been associated with shorter hospitalization and decreased morbidity for these patients. Case reports describe laparoscopic distal pancreatectomy for isolated pancreatic laceration in children. This article presents the experience and results of the first series of totally laparoscopic, spleen-preserving distal pancreatectomies for trauma in children. METHODS: Three children aged 8 to 13 years underwent laparoscopic distal pancreatectomy with splenic preservation for traumatic pancreatic transection within 72 hours of initial injury. Computed tomography imaging in all patients demonstrated complete pancreatic transection. The details of 2 operative techniques used for totally laparoscopic distal pancreatectomy are described. The data for associated injuries, amylase/lipase levels, operative management, postoperative course, length of stay, complications, and follow-up were collected for all patients. RESULTS: All 3 children aged 8, 10, and 13 years underwent laparoscopic distal pancreatectomy without splenectomy within 72 hours of injury (23, 48, and 72 hours). The mechanism of injury was from a bicycle handle, knee to abdomen, and dirt bike handle, respectively. The length of hospital stay was 6, 15, and 7 days with follow-up of 12, 35, and 34 months. The 2 older children underwent pancreatic transection with an endostapler, and the 8-year-old had the pancreatic remnant oversewn by hand. Use of postoperative total parenteral nutrition continued for 0, 13, and 7 days. Complications included an abdominal wall hematoma and prolonged ileus with mild pancreatitis. There were no pancreatic fistulae or insufficiency. All patients are doing well and are asymptomatic from prior injury and laparoscopic distal pancreatectomy. CONCLUSIONS: In the appropriate pediatric patient with traumatic pancreatic transection, a laparoscopic distal pancreatectomy with splenic preservation can be performed safely, with low morbidity and good outcomes. Further studies with larger series of patients with these injuries would be useful.

A review of laparoscopic Nissen fundoplication in children weighing less than 5 kg.

PURPOSE: Minimally invasive procedures in small infants and neonates are being performed in increasing numbers. In this study, we describe our institution's experience with laparoscopic Nissen fundoplications (LNFs) in children weighing less than 5 kg. METHODS: All cases of LNF attempted in children weighing less than 5 kg since January 2003 at a tertiary-care pediatric hospital were reviewed after Institutional Review Board approval. RESULTS: One hundred twenty-two children weighing less than 5 kg underwent LNF during the study period. They ranged from 2 weeks to 3 years of age (mean, 94 +/- 61.3 days) and weighed 1.94 to 4.99 kg (mean, 3.68 +/- 0.77 kg). Twenty-nine percent (n = 35) were neurologically impaired. Eighty-eight percent (n = 107) had concurrent gastrostomy tube placement. Eight (7%) were converted to laparotomy. The average operative time was 112 +/- 46 minutes. Seventy-one percent (n = 87) required intensive care unit use for an average of 14.3 +/- 17.4 days. The average time to start enteral feeds was 2.6 +/- 2.6 days. Thirty-one percent (n = 38) required postoperative mechanical ventilation for an average of 12.0 +/- 20.6 days. The average hospital length of stay was 36.6 +/- 36.0 days (range, 3-175 days). Six patients (5%) had a complication or recurrent gastroesophageal reflux. Three patients had recurrent reflux, one of which underwent another LNF. One patient had a gastric perforation. Another required a redo LNF after a disrupted wrap was noted at a recurrent hiatal hernia repair. Lastly, one patient had bleeding from an accessory hepatic artery with liver retractor placement. CONCLUSIONS: Laparoscopic Nissen fundoplication can safely and effectively be performed in small children (<5 kg) with similar outcomes and rates of complication as previously published reports in larger children. These children, however, do have prolonged intensive care unit and mechanical ventilation use associated with their prematurity and significant comorbidities.

No free ride? The hidden costs of delayed operative management using a spring-loaded silo for gastroschisis.

PURPOSE: The ideal management of gastroschisis (primary vs staged closure) has not yet been established. Despite the ease of silo placement, anecdotal experience shows that silos do not always offer benefit. The aim of this study was to highlight concerns regarding use of spring loaded silos and compare outcomes to primary closure. METHODS: Thirty-seven neonates with gastroschisis treated with either primary (n = 10) or staged closure with a spring-loaded silo (n = 27) were reviewed (1998-2007). Variables included ventilator days, daily intravenous fluid, hospital days, and complication rates. SPSS (SPSS Inc, Chicago, Ill) was used to perform t test and chi(2) analyses (significance P < .05). RESULTS: Survival for primary closure was 100% (10/10) compared to 89% (24/27) for staged closure (P = .548). Patients managed with silos required prolonged ventilation (16.1 +/- 4 days vs 3.6 +/- 1 days; P < or = .05) and greater intravenous fluids on days 3, 4, and 5 of life (132 +/- 25 mL/kg per day vs 104 +/- 18 mL/kg per day; P < or = .01). Although there was no difference in the complication rates between the groups, several problems were evident in the silo group: 15% (4/27) required silo replacement, 44% (12/27) required fascial defect enlargement for silo placement, and 19% (5/27) required mesh at closure. No significant differences in recovery of intestinal function were observed. Three silo patients developed ischemic complications because of vascular insufficiency at the level of the abdominal wall, leading to significant intestinal loss, ventilator and total parenteral nutrition dependence, and increased hospital stay. CONCLUSIONS: Patients managed with a silo had longer ventilator requirements and greater fluid needs. This Specific technical complications leading to bowel ischemia were notable in the silo group. The silo should be carefully placed to avoid bowel twisting and the funnel effect. Larger prospective studies should be performed to provide decision-making criteria for the use of a silo vs primary closure.

Late presentation of congenital diaphragmatic hernia in patients with cystic fibrosis.

Late presentation of congenital diaphragmatic hernia (CDH) is unusual, especially in patients with cystic fibrosis (CF). To our knowledge, cases of CDH in CF patients and the combined effects on lung function have not been previously described. Here we report two cases of late presenting CDH in CF patients and describe effects on lung function. Late presentation of CDH in CF patients can cause gastrointestinal or respiratory symptoms and requires a high index of suspicion as well as proper interpretation of imaging. In patients with CF and CDH, lung function abnormalities could include obstructive, restrictive defects, or combined defects.

Surgical management of ovarian disease in infants, children, and adolescents: a 15-year review.

BACKGROUND: Despite the reported efficacy and the presumed benefits of minimally invasive surgery (MIS) for ovarian lesions in adults, questions remain as to the surgical indications, results, and outcomes for these procedures across pediatric age groups. The aim of this study was to review our experience with the management of ovarian disease in children to determine if there has been a shift in the management of these lesions from open surgery (OS) to an MIS approach in the pediatric population. METHODS: An institutional review board (IRB)-approved retrospective chart review included all patients who underwent surgical management of ovarian disease from January 1, 1992 to July 10, 2007. Patients with ectopic pregnancy, known pelvic inflammatory disease, or concomitant illness requiring operative management at the time of ovarian surgery were excluded. Demographics, clinical signs and symptoms, diagnosis, surgical outcomes, and history of prior abdominal procedures were obtained. Statistical analysis included comparison of means, paired t-test, chi-squared test, and multivariate analysis, where indicated. RESULTS: A total of 231 patients were evaluated in this study, with a mean age of 12.8 years (range, 3 weeks to 20 years). There were 221 (95.7%) benign lesions and 10 (4.3%) were malignant. There were 156 simple or hemorrhagic cysts (70.5%) and 46 mature teratomas (20.8%). Three complications (1.3%) occurred, which were associated with surgery and no mortalities. Abdominal pain (82.3%), nausea or vomiting (24.2%), and abdominal tenderness (10.0%) were the most common presenting symptoms or signs. Operative outcomes for benign disease (n = 221) were compared between MIS and open cases over the entire time period as well as within three consecutive 5-year time intervals. CONCLUSIONS: There was a notable shift toward the management of benign ovarian disease in using MIS techniques over the course of three different 5-year intervals. This approach was also associated with shorter hospital stay, less operative blood loss, and shorter operative times, when compared to an open approach. When indicated, a laparoscopic approach should be performed for presumed benign ovarian disease in children.

Sphingosine-1-phosphate induces early response gene expression in C6 glioma cells.

Sphingosine-1-phosphate (S1P) caused dose-dependent and time-dependent increases in c-fos mRNA. Pretreatment with pertussis toxin (PTX; 100 ng/mlx24 h) reduced c-fos activation by S1P (100 microM-187+/-6% vs. 411+/-27%) and lysophosphatidic acid (LPA; 100 microM-90+/-34% vs. 188+/-41%), but not by sphingosylphosphorylcholine (SPC; 100 microM-390+/-47% vs. 420+/-44%). RT-PCR analysis and sequencing demonstrated the presence of previously unidentified LPA-responsive Endothelial Differentiation Gene (EDG) receptor mRNAs in C6 cells: EDG-2 and EDG-4.

Intercellular calcium waves in cultured enteric glia from neonatal guinea pig.

Enteric glia are important participants in information processing in the enteric nervous system. However, intercellular signaling mechanisms in enteric glia remain largely unknown. We postulated that intercellular calcium waves exist in enteric glia. Primary cultures of enteric glia were isolated from neonatal guinea pig taenia coli. Intracellular calcium in individual cells was quantified with fura-2 AM microfluorimetry. Single-cell stimulation was performed with a micromanipulator-driven glass pipette. Data were expressed as mean +/- SEM and analyzed by Student's t-test. Mechanical stimulation of a single enteric glial cell resulted in an increase in intracellular calcium, followed by concentric propagation to 36% +/- 3% of neighboring cells. Intercellular calcium waves were blocked by depletion of intracellular calcium stores with thapsigargin (1 microM). Pretreatment of enteric glia with the phospholipase C inhibitor U73122 (1 microM) significantly decreased the percentage of cells responding to mechanical stimulation (6% +/- 4%), but had no effect on waves induced by microinjection of the inositol trisphosphate (67% +/- 13% vs. 60% +/- 4% for control). Antagonism of inositol trisphosphate receptor attenuated intercellular calcium waves induced by both mechanical stimulation and microinjection of inositol trisphosphate. Uncoupling of gap junctions with octanol or heptanol significantly inhibited intercellular calcium wave propagation. Pretreatment of enteric glia with apyrase partially attenuated intercellular calcium waves. Our data demonstrate that enteric glial cells are capable of transmitting increases in intracellular calcium to surrounding cells, and that intercellular calcium waves involve a sequence of intracellular and extracellular steps in which phospholipase C, inositol trisphosphate, and ATP play roles.

Regulation of carbachol-induced c-fos mRNA expression in AR42J cells by somatostatin receptor subtypes 1, 2, and 3.

INTRODUCTION: Somatostatin is an inhibitory peptide that exerts its effects tissue-specifically by activating one or more of five receptors (SSTR 1-5). Although several studies have examined which SSTR subtypes control gastrointestinal function, effects of somatostatin on pancreatic gene expression are not well defined. AIM: To examine the effects of somatostatin and newly synthesized selective SSTR agonists on the cholinergically stimulated expression of the immediate early response gene METHODOLOGY AND RESULTS: In pancreatic acinar AR42J cells, polymerase chain reaction analysis revealed that mRNAs for SSTR 1, 2, and 3 were expressed. SSTR 4 and 5 were not detected. When AR42J cells were exposed to the cholinergic agonist carbachol in the presence of somatostatin or selective SSTR agonists, significant and dose-dependent reductions in agonist-induced levels of mRNA were noted. Pretreatment with agonists specific for SSTR 4 or 5 had no inhibitory effects. The inhibitory actions of somatostatin were pertussis toxin-sensitive. In addition, since somatostatin did not affect intracellular calcium homeostasis, the inhibitory actions of somatostatin are independent of calcium signaling. CONCLUSION: The current studies demonstrate that somatostatin inhibits carbachol-induced increases in expression by interacting with somatostatin receptor subtypes 1, 2, and 3. In addition, because somatostatin did not affect intracellular calcium homeostasis, it can be concluded that SSTR actions are independent of carbachol-stimulated calcium signaling.

Cholecystokinin-8 induces intracellular calcium signaling in cultured myenteric neurons from neonatal guinea pigs.

The responsiveness of cultured myenteric neurons to cholecystokinin (CCK-8) was examined using fura-2-based digital microfluorimetric measurement of intracellular calcium ([Ca(2+)](i)). CCK-8 (10(-10)-10(-6)M) evoked concentration-dependent increases in percentage of neurons responding (8-52%) and delta[Ca(2+)](i) (76-169 nM). Gastrin (1 microM) also induced an increase in [Ca(2+)](i) in 29+/-6% of neurons (delta[Ca(2+)](i): 71+/-3 nM). L-364,718, an antagonist for the CCK-A receptor, blocked [Ca(2+)](i) response to CCK-8. Removal of extracellular calcium eliminated CCK-induced [Ca(2+)](i) increments, as did the addition of the calcium channel inhibitors nickel (1mM) and lanthanum (5mM). Nifedipine (1-50 microM) dose-dependently attenuated CCK-caused [Ca(2+)](i) responses. CCK evokes [Ca(2+)](i) signaling in myenteric neurons by the influx of extracellular calcium, likely through L-type calcium channels.