Microbicidal activities of Salmonella typhimurium- and interferon-gamma-activated mouse peritoneal macrophages

Activation of mouse peritoneal macrophages during infection of mice by various facultative intracellular bacteria and after intravenous injection of recombinant interferon-gamma (rIFN-gamma) was studied. Macrophage activation was demonstrated on the basis of three different criteria, i.e. inhibition of Toxoplasma gondii proliferation, enhanced release of H2O2 and increased expression of Ia antigen. Macrophages activated during an infection with Salmonella typhimurium showed no enhanced salmonellacidal or listericidal activity relative to control macrophages, whereas Listeria-activated macrophages killed Listeria but not Salmonella faster than control macrophages. The rate of proliferation of Salmonella in spleen and liver of activated mice was comparable to the proliferation in the organs of control mice. rIFN-gamma-activated macrophages displayed neither an enhanced salmonellacidal nor an enhanced listericidal activity. When high numbers of Listeria were injected intravenously the proliferation in spleen and liver of rIFN-gamma-treated and control mice was similar. The proliferation of Listeria in the liver of rIFN-gamma-treated mice was less than in control mice when 1 LD50 or lower numbers of bacteria were injected. It is concluded that peritoneal macrophages become activated during infections of mice with various intracellular pathogens. However, these activated macrophages do not show enhanced bactericidal activity against all bacteria. Furthermore, rIFN-gamma is not sufficient to enhance the listericidal activity of macrophages.     

Determinants of attrition in a pediatric healthy lifestyle intervention: The CIRCUIT program experience

IntroductionAttrition in pediatric weight management programs is notoriously high. Greater understanding of its determinants is needed to inform retention strategies. We identified determinants of attrition in CIRCUIT, a healthy lifestyle intervention program for youth at risk of cardiovascular disease.MethodsA one-arm intervention study of children aged 4-18 years who initiated the CIRCUIT program in the first five years of its existence (N = 403). We defined attrition as attending the baseline visit but ceasing attendance prior to the 1-year follow-up. Potential determinants of dropout included the child’s age, sex, ethnicity, body mass index (BMI) z-score, family socio-demographic characteristics, and estimated driving time to the program, all measured at baseline. Associations were estimated bivariately, using chi-squared- and t-tests, and simultaneously in a multivariable logistic regression model.ResultsOf the 403 participants who started the program, 198 (49%) dropped out within 12 months of enrollment. Youth who dropped out were older (mean age 12.8y vs. 11.3y; p < 0.01), were less likely to live with both parents (62% vs. 71%; p = 0.05), and to have mothers who had completed high school (79% vs. 88%; p = 0.01). No group differences were observed for sex, ethnicity, baseline BMI z-score, fathers’ education, or driving time to the program. In multivariate models, only older age at initiation of the intervention (OR: 1.2; CI: 1.1,1.3) and lower maternal education (OR: 2.0; CI: 1.0,3.8) were associated with dropout.ConclusionImproved tailoring of interventions to older pediatric participants and to families of lower maternal education may help reduce attrition in CIRCUIT and similar lifestyle intervention programs.     

Dampened Muscle mTORC1 Response Following Ingestion of High-Quality Plant-Based Protein and Insect Protein Compared to Whey

Increased amino acid availability acutely stimulates protein synthesis partially via activation of mechanistic target of rapamycin complex 1 (mTORC1). Plant-and insect-based protein sources matched for total protein and/or leucine to animal proteins induce a lower postprandial rise in amino acids, but their effects on mTOR activation in muscle are unknown. C57BL/6J mice were gavaged with different protein solutions: whey, a pea–rice protein mix matched for total protein or leucine content to whey, worm protein matched for total protein, or saline. Blood was drawn 30, 60, 105 and 150 min after gavage and muscle samples were harvested 60 min and 150 min after gavage to measure key components of the mTORC1 pathway. Ingestion of plant-based proteins induced a lower rise in blood leucine compared to whey, which coincided with a dampened mTORC1 activation, both acutely and 150 min after administration. Matching total leucine content to whey did not rescue the reduced rise in plasma amino acids, nor the lower increase in mTORC1 compared to whey. Insect protein elicits a similar activation of downstream mTORC1 kinases as plant-based proteins, despite lower postprandial aminoacidemia. The mTORC1 response following ingestion of high-quality plant-based and insect proteins is dampened compared to whey in mouse skeletal muscle.     

Decrease of mucosal glutamine concentration in the nutritionally depleted patient

A diminished glutamine delivery by peripheral tissues is suggested to play an important role in the etiology of postoperative complications of nutritionally depleted patients. Decreased glutamine supply to the gut mucosa in these nutritionally depleted patients may have important consequences for the integrity of the gut mucosa barrier. To evaluate whether glutamine concentration in the gut mucosa of depleted patients is altered, patients with either a fat-free mass index below 90% or percentage ideal body weight below 90% as a result of weight loss were studied. 22 patients admitted to the University Hospital Maastricht and 14 controls were studied. After an overnight fast, venous blood was sampled and duodenal biopsies were obtained by endoscopy. Plasma and tissue amino acids were measured. Fat-free mass was determined by bioelectrical impedance measurement. In 10 depleted patients glutamine concentration in the duodenal mucosa was 2883 +/- 250 mumol/kg dry weight. Concentration of alanine was 2570 +/- 263 mumol/kg dry weight. In the non-depleted patients glutamine and alanine concentrations were respectively 3463 +/- 171 mumol/kg dry weight and 3540 +/- 315 mumol/kg dry weight. Concentrations in controls were 3296 +/- 176 mumol/kg dry weight for glutamine and 3682 +/- 372 mumol/kg dry weight for alanine. Concentrations for alanine and glutamine were significantly lower in depleted patients compared to non-depleted patients (p < 0.05). Also, alanine and glutamine concentrations were significantly correlated with percentage ideal body weight (r=0.43, p < 0.005 for glutamine and r=0.62, p < 0.001 for alanine) and fat-free mass index (r=0.42, p < 0.05 for glutamine and r=0.48, p < 0.01 for alanine) This study suggests that in patients depletion appears to be related to decreased plasma and mucosa glutamine and alanine concentrations.     

Laser assisted ratio analyser 13C-urea breath testing, for the detection of H. pylori: a prospective diagnostic European multicentre study

BACKGROUND: Novel technology based on laser optogalvanic spectroscopy called the LARA (Laser Assisted Ratio Analyser) system was developed to measure 12C/13C ratios in breath samples using stable 13C isotopes, to detect Helicobacter pylori infection. AIM: To determine the sensitivity and specificity of the 13C-LARA-urea breath test in the detection of H. pylori infection in a prospective European multicentre trial; FDA-and EMEA-approved. METHODS: Consecutive dyspeptic patients underwent diagnostic gastroscopy with biopsies for culture and histopathology, to detect H. pylori infection (gold standard). Subsequently, the LARA-urea breath test was performed using either a system without a cold trap (part I) or a system with a cold trap (part II). In both instances baseline, 30-min and 60-min breath samples were collected. The optimum cut-off level for 12C/13C ratios was determined by Receiver Operator Characteristics analysis. RESULTS: In part I, 544 out of 604 patients were evaluable (low CO2: 47; withdrawn: 13). 284 out of 544 patients (52%) were H. pylori-positive according to the gold standard. The sensitivity of the LARA-urea breath test was 95% and the specificity 94%. In part II, 257 out of 272 were evaluable (low CO2: 14; withdrawn: 1). Sensitivity and specificity were 93% and 96%, respectively. CONCLUSION: The LARA-technology represents an accurate and non-invasive testing system for the detection of H. pylori infection. Its major advantages are the use of stable 13C isotope, the high throughput of samples and the easy means of collecting, storing and transporting the samples, thus making the system convenient to both patient and clinician.     

Helicobacter pylori and gastro-oesophageal reflux disease: association and clinical implications. To treat or not to treat with anti-H. pylori therapy?

BACKGROUND: It has been reported that patients are at risk of developing reflux oesophagitis after successful anti-Helicobacter pylori therapy, and the presence of the bacterium might be protective against the development of reflux oesophagitis. METHODS: Review of the literature. RESULTS: H. pylori is relevant to the management of oesophagitis because it increases the pH-elevating effect of proton-pump inhibitors. which increase the tendency of H. pylori gastritis to progress to atrophic gastritis, and because eradication of H. pylori increases the likelihood of oesophagitis. H. pylori increases basal gastrin levels, basal acid output, meal-stimulated maximal acid output and 24-h intragastric acidity. The effects on gastric acid production depend on the distribution of gastritis in the stomach. CONCLUSION: H. pylori eradication may induce or exacerbate gastro-oesophageal reflux by its influence on gastric acidity and the antisecretory action of proton-pump inhibitors.