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Maternal nutrition, gut microbiome composition, and metabolites derived from gut microbiota are closely related to the development of hypertension in offspring. A plethora of metabolites generated from diverse tryptophan metabolic pathways show both beneficial and harmful effects. Butyrate, one of the short-chain fatty acids (SCFAs), has shown vasodilation effects. We examined whether sodium butyrate administration in pregnancy and lactation can prevent hypertension induced by a maternal tryptophan-free diet in adult progeny and explored the protective mechanisms. Pregnant Sprague-Dawley rats received normal chow (CN), tryptophan-free diet (TF), sodium butyrate 400 mg/kg/d in drinking water (CNSB), or TF diet plus sodium butyrate (TFSB) in pregnancy and lactation. Male offspring were sacrificed at the age of 16 weeks (n=8 per group). Compared with normal chow, offspring exposed to the maternal tryptophan-free diet had markedly increased blood pressure, associated with activation of the renin-angiotensin system (RAS). Treatment with sodium butyrate rescued maternal TF-exposed offspring from hypertension. The protective effect of sodium butyrate is related to alterations to microbiome composition, increased renal expression of SCFA receptor G protein-coupled receptor 41 (GPR41) and GPR109A, and restoration of RAS balance. In summary, these results suggest that sodium butyrate protects against maternal TF-induced offspring hypertension, likely by modulating gut microbiota, its derived metabolites, and the RAS.

Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.

A maternal high-fat (HF) diet sensitizes offspring to the adverse effects of postnatal HF intake and can lead to metabolic dysregulation. Resveratrol, a natural polyphenolic compound found in grapes and red wine, could help to relieve metabolic syndrome dysregulation. Since the gut microbiota is known to be closely related to metabolic homeostasis, this study aimed to investigate the impact of a combination of maternal and postweaning HF diets on the gut microbiota and whether resveratrol could relieve the gut dysbiosis associated with metabolic dysregulation. Sprague-Dawley dams were sustained on either a chow or HF diet before mating, during pregnancy and during lactation. Their offspring were randomly fed chow or a HF diet after weaning. Four experimental groups were generated: CC (maternal/postnatal chow diet), HC (maternal HF/postnatal chow diet), CH (maternal chow/postnatal high-fat diet) and HH (maternal/postnatal HF diet). A fifth group consisted of HH with resveratrol treatment. We found that both maternal and postnatal HF exposure has a distinct effect on the gut microbiota metagenome of offspring. Maternal HF diet exposure decreased plasma acetate, propionate and butyrate level, while postnatal HF diet exposure decreased plasma acetate level in adult life. The metabolic dysregulation programed by the maternal and postnatal HF diets was related to the relevant gut microbiota. Resveratrol treatment ameliorated the altered plasma propionate level related to maternal HF and postnatal HF diet treatment. Resveratrol treatment also improved most of the altered metabolic dysregulation and related dysbiosis programmed by maternal and postnatal HF diet exposure.

Background/Purpose: Viral infections and innate immunity signaling, especially Toll-like receptor 7 (TLR7) have been implicated in the pathogenesis of biliary atresia (BA). Administration of rhesus rotavirus-type A to newborn Balb/c mice produces inflammatory obstruction of bile ducts, which resembles human BA. However, whether activation of TLR7 signaling plays a role in neonatal hepatobiliary injury remains to be investigated. Methods: TLR7 agonist, imiquimod (R837), was intraperitoneally administered to Balb/c mice within 24 hours of birth and then every other day. Morphological and histological injuries of liver and gallbladder were examined at 2 weeks. Hepatic messenger RNA expression of TLR7 signaling was studied. Terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling staining was used to delineate hepatobiliary apoptosis upon TLR7 stimulation. Results: TLR7 agonist, imiquimod, induced hypoplasia of the biliary system of neonatal Balb/c mice both in atrophic gallbladder and in paucity of intrahepatic bile ducts. There was significantly higher hepatic expression of TLR7 and downstream innate immunity-mediated interferon regulatory factor 7, interferon-α, and tumor necrosis factor-α. In addition, terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling-positive cells in the liver were increased after injections of TLR7 agonist. Conclusion: The results demonstrate that TLR7 activation may trigger innate immunity pathways and induce apoptosis and hypoplasia of neonatal biliary trees in Balb/c mice. The novel findings give an implication of pathogenesis of infantile cholestasis, such as BA. Keywords: animal model, Balb/c mice, biliary atresia, infantile cholestasis, innate immunity, toll-like receptor 7

Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality. Cholestatic liver injury is associated with a downregulation of hepcidin expression levels. In fact, hepcidin has an important antimicrobial effect, especially against Escherichia coli. It is unknown whether supplementing recombinant hepcidin is effective in alleviating cholestasis-induced liver injury and mortality in mice with superimposed sepsis. A mouse model of cholestasis was developed using extrahepatic bile duct ligation for 3 days. In addition, sepsis due to E. coli 0111:B4 lipopolysaccharide (LPS) was induced in the model. The serum levels of total bilirubin, AST, ALT, and LDH and the mRNA levels of IL-1β, TNF-α, and MCP-1 in the liver were significantly higher in the OJ mice receiving LPS than in the sham-operated mice receiving LPS. Compared to the OJ mice receiving LPS, the hepcidin-pretreated OJ mice receiving LPS showed a significant decrease in the above mentioned parameters, as well as a reversal in the downregulation of LC3B-II and upregulation of cleaved caspase-3; this, in turn, led to significantly decreased lethality in 24h. In conclusion, these results indicate that hepcidin pretreatment significantly reduced hepatic proinflammatory cytokine expression and liver injury, leading to reduced early lethality in OJ mice receiving LPS. Enhanced autophagy and reduced apoptosis may account for the protective effects of hepcidin.

Ectopic pelvic kidney is a rare developmental anomaly. Ectopic pelvic kidney can present without the characteristic symptoms associated with the urinary tract pathology. Ectopic pelvic kidney is usually unknown, and nonspecific vague abdominal comfort maybe the only symptom. Early detection and recognition of an ectopic kidney can prevent long-term complications. We report a 3-year-5-month-old girl with ectopic pelvic kidney who experienced intermittent episodes of lower abdominal pain for about 1 month. Abdominal ultrasound, computed tomography, and intravenous pyelography demonstrated a pelvic kidney. Thereafter, the urinalysis showed pyuria (white blood cell 20/high power field), and urine culture grew Escherichia coli. We emphasize that pelvic kidney should be considered in patients presenting unexplained vague abdominal pain, especially in pediatric patients who had intermittent recurrent episodes.

Background: To investigate whether the effect of hyperglycemia on mitochondrial DNA (mtDNA) content is tissue-specific. Method: We compared the mtDNA contents in leg muscle, blood vessel, and peripheral leucocytes in seventeen patients with type 2 diabetes (T2DM) with those of seven controls. We measured 8-hydroxydeoxyguanosine (8-OHdG) expression in the muscles and thiobarbituric acid reactive substance (TBARS) in sera to evaluate oxidative stress. Immunohistochemical detection of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-a), mitochondrial transcription factor A (Tfam), and apoptosis were performed in the muscle tissue. Results: The mtDNA copy number was highest in muscle tissue, followed by blood vessel tissue, and lowest in leucocytes in both the diabetic and control subjects. The diabetic patients had less mtDNA content in the muscle than the controls (2.86 � 0.33 vs. 3.20 � 0.14, P = 0.025), but more mtDNA content in the leucocytes (2.25 � 0.26 vs. 1.98 � 0.06, P = 0.04). In both groups, there was a positive correlation between muscle tissue mtDNA content and the expression of 8-OHdG. Patients with T2DM had significantly increased 8-OHdG and TUNEL labeling index and non-significant increases in the expression of PGC1-a and Tfam. Conclusion: Oxidativestressstimulatesmitochondrialbiogenesisbutinducesagreaterdegree of apoptosis in diabetic patients, resulting in a decrease in muscle tissue mtDNA content.

Campylobacter has been recognized as the common cause of bacterial gastroenteritis in many countries. Increasing erythromycin resistance in Campylobacter jejuni infection is noted recently, but severe case was rarely reported. In this study, we aimed to clarify the clinical significance of the resistant strain of C jejuni in children. We reviewed the charts of children who were diagnosed with C jejuni enteritis in our hospital from January 2000 to December 2005, including 326 patients (117 males and 209 females). All the cases had positive stool culture. We divided them into two groups, the sensitive group (a total of 306 cases) and resistant group (a total of 20 cases), according to the drug sensitivity. We analyzed the clinical manifestations and laboratory data between the two groups. The mean age was 3.79±3.24 years in the sensitive group and 3.03±2.84 years in the resistant group. There was no significant difference between the two groups in clinical presentations and laboratory examinations. No mortality was found, and one case was initially presented with colonic perforation. This report demonstrates that infection by erythromycin-resistant strains of C jejuni has no clinical significance in children, despite the probably increased emergence of erythromycin resistance.

BackgroundOmental infarction is a rare occurrence in children. It is often diagnosed during surgery for suspected appendicitis. This study investigated the use of clinical and laboratory data for distinguishing between omental infarction and acute appendicitis.MethodsSeven patients with surgically and pathologically proven omental infarction and 28 age- and sex-matched patients with acute appendicitis were included in this study. The clinical characteristics, imaging study results and laboratory data were analyzed.ResultsAll 35 patients had right lower quadrant abdominal pain at presentation. The frequency of nausea and fever were significantly lower in the omental infarction group compared with the acute appendicitis group (p< 0.001 and p= 0.018, respectively). In laboratory studies, the white blood cell count, C-reactive protein value and neutrophil percentage were all higher in the acute appendicitis group compared with the omental infarction group (p= 0.001, p< 0.001, and p= 0.008, respectively). It was possible to separate patients with omental infarction from those with acute appendicitis based on a neutrophil percentage of less than 77% (sensitivity 100%, specificity 100%).ConclusionsResults of the current study suggest that omental infarction should be considered as a possible diagnosis in patients presenting with right lower quadrant abdominal pain without nausea or fever, and with a neutrophil percentage below 77%.

Background The incidence of end-stage renal disease (ESRD) in Taiwan is the highest in the world. However, epidemiological features of earlier chronic kidney disease (CKD) have not been investigated. Methods Since implementation of the National Health Insurance Program in 1995, more than 96% of the population in Taiwan has been enrolled. A nationally representative cohort of 200,000 individuals randomly sampled from the National Health Insurance enrollees was followed up from 1996 to 2003. Clinical conditions were defined by using diagnostic codes. The prevalence and incidence of clinically recognized CKD were assessed. We also identified risk factors associated with the development of CKD. Results The prevalence of clinically recognized CKD increased from 1.99% in 1996 to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100 person-years. The multivariate model indicates that age is a key predictor of CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with the group younger than 20 years. Other factors associated with increased risk for the development of CKD include diabetes, hypertension, hyperlipidemia, and female sex. Conclusion The prevalence and incidence of CKD in Taiwan are relatively high compared with other countries. Our finding provides a reasonable explanation for the subsequent epidemic of ESRD in Taiwan. Further study is needed to identify the entire burden of CKD and the effectiveness of risk-factor modification.

Departments of *Pediatrics, †Pathology, ‡Radiology, and §Pediatric Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan Reprint Address: Mao-Meng Tiao, MD, Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, 123 Ta-Pei Road, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan