Pilot Study Measuring the Novel Satiety Hormone, Pro-Uroguanylin, in Adolescents With and Without Obesity.

OBJECTIVE: Disruption of satiety signaling may lead to increased caloric intake and obesity. Uroguanylin, the intestinal hormone, travels as a precursor to the central nervous system where it activates guanylyl cyclase C and stimulates pro-satiety neurons. Rodent studies have demonstrated that guanylyl cyclase C-knockout mice overeat and have increased weight gain versus wild-type mice and hyper-caloric obesity diminishes uroguanylin expression. We measured circulating plasma pro-uroguanylin, along with other gastrointestinal peptides and inflammatory markers, in human adolescents with and without obesity, as a pilot study. We hypothesized that adolescents with obesity would have less circulating pro-uroguanylin than adolescents without obesity have. METHODS: We recruited 24 adolescents (age 14-17 years) with and without obesity (body mass index >95% or body mass index <95%) and measured plasma pro-uroguanylin at fasting and successive time points after a meal. We measured 3 other satiety hormones and 2 inflammatory markers to characterize overall satiety signaling and highlight any link between uroguanylin and inflammation. RESULTS: Female adolescents with obesity had lower circulating pro-uroguanylin levels than female adolescents without obesity; we observed no difference in males. Other measured gastrointestinal peptides varied in their differences between cohorts. Inflammatory markers were higher in female participants with obesity. CONCLUSIONS: In adolescents with and without obesity, we can measure circulating pro-uroguanylin levels. In female adolescents without obesity, levels are particularly higher. Pro-uroguanylin secretion patterns differ from other circulating gastrointestinal peptides. In female adolescents with obesity, inflammation correlates with decreased pro-uroguanylin levels.

The role of gastric pepsin in the inflammatory cascade of pediatric otitis media.

IMPORTANCE: Otitis media is characterized as an ongoing inflammation with accumulation of an effusion in the middle ear cleft. The molecular mechanisms underlying the pathogenesis, particularly the inflammatory response, remain largely unknown. We hypothesize that aspiration of gastric contents into the nasopharynx may be responsible for the initiation of the inflammatory process or aggravate a preexisting condition. OBJECTIVE: To investigate the correlation of gastric pepsin A with inflammatory cytokines, bacterial infection, and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 129 pediatric patients undergoing myringotomy with tube placement for otitis media at a tertiary care pediatric hospital. MAIN OUTCOMES AND MEASURES: Ear samples were tested for pepsin A; cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor; and bacterial culture inoculation. Data were analyzed by descriptive statistics and regression analysis to identify risk factors for the presence of pepsin A and to correlate pepsin A levels with cytokine levels, infection status, and clinical outcomes. RESULTS: Of the 129 patients, 199 ear samples were obtained; 82 samples (41%) and 64 patients (50%) were positive for pepsin A as measured by immunoassay. Pepsin A positivity correlated with age younger than 3.0 years (mean [SD], 2.3 [2.1] years in the positive group vs 3.3 [3.0] years in the negative group) and with all 3 cytokine levels (mean [SD] tumor necrosis factor, 29.5 [45.9] pg/mL in the positive group vs 13.2 [21.6] pg/mL in the negative group; IL-6, 6791.7 [9389.1] pg/mL in the positive group vs 2849.9 [4066.3] pg/mL in the negative group; and IL-8, 6828.2 [8122.3] pg/mL in the positive group vs 2925.1 [3364.5] pg/mL in the negative group [all P < .05]); however, logistic regression analysis showed that only IL-8 (odds ratio, 3.96; 95% CI, 1.3-12.0; P = .02) and age (odds ratio, 3.83; 95% CI, 1.2-12.7; P = .03) were significant independent variables. No statistically significant association was found with other parameters. Multiple linear regressions revealed that the levels of pepsin A were correlated with IL-8 levels (R2 = 0.248; P < .001) and the need for second or third tubes 6 to 12 months after the first (R2 = 0.102; P = .006). The presence of pepsin A in the middle ear was not associated with increased bacterial infection. Interleukin 8 was independent and significantly associated with both pepsin A levels and bacterial infection (R2 = 0.144 and 0.263, respectively; P = .001 for both). CONCLUSIONS AND RELEVANCE: Extraesophageal reflux as indicated by the presence of pepsin A is closely involved in the middle ear inflammatory process and may worsen the disease in some children; however, a proof of cause and effect between extraesophageal reflux and middle ear inflammation requires further investigation.

Ghrelin and obestatin levels in children with failure to thrive and obesity.

OBJECTIVES: Ghrelin and obestatin are 2 gastric hormones with opposite effects on food intake and body weight. We investigated plasma ghrelin and obestatin in children with failure to thrive (FTT) and obesity as compared with age-matched controls. METHODS: A total of 63 children were included in the study: 13 with FTT, 17 with obesity, and 33 age-matched controls. Children fasted for at least 8 hours before specimen collection. Both hormones were measured using commercially available enzyme immunoassay kits. RESULTS: Ghrelin and obestatin levels in children with FTT were not significantly different from that of the age-matched controls (P >0.05). In children with obesity, the total ghrelin levels were significantly lower (P = 0.0003) and the obestatin levels significantly higher (P = 0.029) compared with those in controls. In the control group, the fasting ghrelin level was significantly higher in the younger (<3 years) than in the older children (>3 years; P = 0.0004). Obestatin levels correlated positively with weight-for-age percentiles in the obese group (P = 0.011) and negatively in the control group >3 years (P = 0.019). CONCLUSIONS: Compared with the levels in age-matched controls, fasting ghrelin and obestatin levels did not differ significantly in children with FTT. In the children with obesity, the decreased ghrelin and increased obestatin levels suggest a possible adaptive process to positive energy balance. Ghrelin had pronounced age-related changes, and obestatin was associated with the weight status. This may suggest that these 2 hormones use different mechanisms to regulate energy balance and weight.

An automated method for the determination of intestinal disaccharidase and glucoamylase activities.

Determination of disaccharidase and glucoamylase activities is important for the diagnosis of intestinal diseases. We adapted a widely accepted manual method to an automated system that uses the same reagents reaction volumes, incubation times, and biopsy size as the manual method. A dye was added to the homogenates as the internal quality control to monitor the pipetting precision of the automated system. When the automated system was tested using human intestinal homogenates, the activities of all the routinely tested disaccharidases, including lactase, maltase, sucrase, and palatinase, as well as the activity of glucoamylase, showed perfect agreement with the manual method and were highly reproducible. The automated analyzer can perform the same routine assays of disaccharidases and glucoamylase with high consistency and accuracy and reduce testing costs by performing a larger sample size with the same number of staff. Additional developments, such as barcoding and built-in plate reading, would result in a completely automated system.

Cytokine release, pancreatic injury, and risk of acute pancreatitis after spinal fusion surgery.

Acute pancreatitis after posterior spinal fusion in children is associated with high intraoperative blood loss. Inflammation, oxidative stress, and pancreatitis markers were assessed during this period. Five of the 17 patients studied developed acute pancreatitis 3-7 days after surgery. Intraoperative blood loss (4850 +/- 2315 vs 1322 +/- 617 ml) and peak tumor necrosis factor alpha levels (15.29 +/- 5.3 vs 8.27 +/- 4.6 pg/ml) in the immediate postoperative period were significantly higher in these five patients than in controls, respectively. No differences were noted in serum interleukin 8, interleukin 6, pancreatis-associated protein, or urine malondialdehyde levels. Urine trypsin-associated peptide, elevated initially in all patients, was significantly higher in the acute pancreatitis group at diagnosis. Length of stay was significantly longer in the acute pancreatitis group. Greater blood loss and peak tumor necrosis factor alpha are associated with subsequent risk of acute pancreatitis, suggesting a role of ischemia-reperfusion injury.

Short-term effect of epidermal growth factor on glucose uptake in endoscopic biopsies.

Epidermal growth factor (EGF) up-regulation of glucose absorption via increased Na+/glucose co-transporter (SGLT-1) activity has previously been described in rabbit jejunal brush-border membrane and in differentiated Caco-2 cells. The goal of the present study was to assess the in vitro effect of EGF (200 ng/ml) on glucose uptake in human mucosal specimens, and we describe a simple procedure that uses endoscopic biopsies for short-term gludose uptake measurements. Uptake values for the EGF-treated biopsies ranged from 2.7 to 29.0, with a mean uptake of 10.65, while uptake values for the untreated biopsies ranged from 0.9 to 17.5, with a mean uptake of 7.99 (P < 0.05, paired t test). This early effect of EGF on human enterocytes may have important therapeutic implications. A role in increasing the rate of internal rehydration is suggested.