Gut at Risk: Epithelial nutrient digestion and absorption, protection and defence

The newborn’s transition from intrauterine to extrauterine life is marked by a chain of rapid and complex physiological changes. For example, this adaptive process is characterised by the transition from foetal ‘respiratory’ activity to normal ventilation.1 Onset of respiration stimulates a series of cardiopulmonary changes – e.g. increase in pulmonary blood flow and closure of the foramen ovale and ductus arteriosus – as the newborn makes the transition from foetal to neonatal circulation. Furthermore, in utero, the foetus is dependent on the placenta and swallowed amniotic fluid for its nutrition. Pivotal, too, is the physiological transition that occurs as the foetus, once born, replaces the placenta with his gastrointestinal (GI) tract to obtain nutrition. Enteral feeding, preferably breast milk, is vital for optimal growth and d

Partial hexokinase II knockout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice

Cellular studies have demonstrated a protective role of mitochondrial hexokinase against oxidative insults. It is unknown whether HK protective effects translate to the in vivo condition. In the present study, we hypothesize that HK affects acute ischemia–reperfusion injury in skeletal muscle of the intact animal. Male and female heterozygote knockout HKII (HK(+/-)), heterozygote overexpressed HKII (HK(tg)), and their wild-type (WT) C57Bl/6 littermates mice were examined. In anesthetized animals, the left gastrocnemius medialis (GM) muscle was connected to a force transducer and continuously stimulated (1-Hz twitches) during 60 min ischemia and 90 min reperfusion. Cell survival (%LDH) was defined by the amount of cytosolic lactate dehydrogenase (LDH) activity still present in the reperfused GM relative to the contralateral (non-ischemic) GM. Mitochondrial HK activity was 72.6 ± 7.5, 15.7 ± 1.7, and 8.8 ± 0.9 mU/mg protein in male mice, and 72.7 ± 3.7, 11.2 ± 1.4, and 5.9 ± 1.1 mU/mg in female mice for HK(tg), WT, and HK(+/-), respectively. Tetanic force recovery amounted to 33 ± 7% for male and 17 ± 4% for female mice and was similar for HK(tg), WT, and HK(+/-). However, cell survival was decreased (p = 0.014) in male HK(+/-) (82 ± 4%LDH) as compared with WT (98 ± 5%LDH) and HK(tg) (97 ± 4%LDH). No effects of HKII on cell survival was observed in female mice (92 ± 2% LDH). In conclusion, in this mild model of acute in vivo ischemia–reperfusion injury, a partial knockout of HKII was associated with increased cell death in male mice. The data suggest for the first time that HKII mediates skeletal muscle ischemia–reperfusion injury in the intact male animal

Early Nutrition: Prevention of Celiac Disease?

Transplantation and immunomodulatio

Comparison of Patients' and Doctors' Reports on Health-related Quality of Life in Celiac Disease

Transplantation and immunomodulatio

The use of knowledge translation in developing evidence for public health policy and practice: a staged, multi-methods study in England, 2007-2009

We previously demonstrated that hexokinase (HK) II plays a key role in the pathophysiology of ischemia-reperfusion (I/R) injury of the heart (Smeele et al. Circ Res 108: 1165-1169, 2011; Wu et al. Circ Res 108: 60-69, 2011). However, it is unknown whether HKII also plays a key role in I/R injury and healing thereafter in skeletal muscle, and if so, through which mechanisms. We used male wild-type (WT) and heterozygous HKII knockout mice (HKII(+/-)) and performed in vivo unilateral skeletal muscle I/R, executed by 90 min hindlimb occlusion using orthodontic rubber bands followed by 1 h, 1 day, or 14 days reperfusion. The contralateral (CON) limb was used as internal control. No difference was observed in muscle glycogen turnover between genotypes at 1 h reperfusion. At 1 day reperfusion, the model resulted in 36% initial cell necrosis in WT gastrocnemius medialis (GM) muscle that was doubled (76% cell necrosis) in the HKII(+/-) mice. I/R-induced apoptosis (29%) was similar between genotypes. HKII reduction eliminated I/R-induced mitochondrial Bax translocation and oxidative stress at 1 day reperfusion. At 14 days recovery, the tetanic force deficit of the reperfused GM (relative to control GM) was 35% for WT, which was doubled (70%) in HKII(+/-) mice, mirroring the initial damage observed for these muscles. I/R increased muscle fatigue resistance equally in GM of both genotypes. The number of regenerating fibers in WT muscle (17%) was also approximately doubled in HKII(+/-) I/R muscle (44%), thus again mirroring the increased cell death in HKII(+/-) mice at day 1 and suggesting that HKII does not significantly affect muscle regeneration capacity. Reduced HKII was also associated with doubling of I/R-induced fibrosis. In conclusion, reduced muscle HKII protein content results in impaired muscle functionality during recovery from I/R. The impaired recovery seems to be mainly a result of a greater susceptibility of HKII(+/-) mice to the initial I/R-induced necrosis (not apoptosis), and not a HKII-related deficiency in muscle regeneration

Exigências de treonina digestível para leitoas mantidas em ambiente termoneutro dos 15 aos 30 kg Digestible threonine requirement for gilts maintained in thermoneutral environment from 15 to 30 kg

Este estudo foi conduzido com o objetivo de avaliar as exigências de treonina digestível em rações para leitoas no período de 15 aos 30 kg, mantidas em ambiente termoneutro. Setenta leitoas, mestiças, com peso inicial de 15,1 ± 0,4 kg, foram distribuídas em delineamento experimental de blocos ao acaso, com cinco tratamentos (níveis de treonina digestível), sete repetições e dois animais por unidade experimental. Os tratamentos corresponderam aos níveis de 0,54; 0,58; 0,61; 0,65 e 0,69% de treonina digestível. Os níveis de treonina digestível da ração aumentaram o ganho de peso diário de forma quadrática até o nível de 0,61% e a conversão alimentar até o nível de 0,62%. As deposições de proteína e gordura na carcaça dos animais também se elevaram de forma quadrática, atingindo valor máximo no nível de 0,61%. Constatou-se efeito linear dos tratamentos sobre os pesos absoluto e relativo do intestino. O nível calculado de 0,62% de treonina digestível, correspondente a uma relação com a lisina digestível de 67% e a um consumo diário de 7,11 g, proporcionou melhor desempenho de leitoas mantidas em ambiente termoneutro dos 15 aos 30 kg.<br>This study was carried out to evaluate the requirements of digestible threonine in diets of gilts from 15 to 30kg, maintained in thermoneutral environment. Seventy crossbreed gilts with an initial weight of 15.1 ± 0.4 kg were used in a randomized blocks design, with five treatments (levels of digestible threonine), seven replicates and two animals per experimental unity. The treatments corresponded to the levels of 0.54, 0.58, 0.61, 0.65, e 0.698% of digestible threonine. Digestible threonine levels in the diet increased the daily weight gain in a quadratic way up to the level of 0.61% and the feed:gain ratio up to the level of 0.62%. Protein and fat deposition rates also increased in a quadratic way reaching maximum value up to the level of 0.61%. A linear effect of the treatments was evidenced on the absolute and relative weights of the intestine. The calculated level of 0.62% of digestible threonine corresponding to a relation with digestible lysine of 67% and a daily intake of 7.11 g, provided better performance of gilts maintained in a thermoneutral environment from 15 to 30 kg

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice

Background &amp; Aims The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. Methods We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. Results Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61–99.99); the PPV was 100.00 (95% CI, 98.68–100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67–99.96) to 100.00 (95% CI, 99.23–100.00). Conclusions Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555. © 2017 AGA Institut