Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers.

Apraglutide (FE 203799) is a glucagon-like peptide-2 (GLP-2) analog under development for the treatment of intestinal failure associated with short bowel syndrome (SBS-IF) and graft-versus-host disease (GvHD). Compared with native GLP-2, apraglutide has slower absorption, reduced clearance, and higher protein binding, enabling once-weekly dosing. This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) profile of apraglutide in healthy adults.

Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial.

Background: A defining feature of prolonged critical illness is muscle wasting, leading to impaired recovery. Supplementation with a tailored blend of amino acids may bolster the innate gut defence, promote intestinal mucosa repair and limit muscle loss.

Methods: This was a monocentric, randomized, double-blind, placebo-controlled study that included patients with sepsis or acute respiratory distress syndrome.

Complications Requiring Intensive Nutritional Care After Bariatric Surgery Result in More Long-Term Weight Loss but Has No Impact on Nutritional Deficiencies and Depression-Anxiety Scores.

Purpose: Bariatric surgery is associated with significant weight loss and improvement in comorbid conditions but in rare cases can expose to complications requiring intensive nutritional care (INC). INC in this context is poorly described and no data are available concerning long-term impact.

Materials And Methods: We retrospectively reviewed charts of bariatric patients who were hospitalized in our institution between 2013 and 2018.

Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use.

L-Citrulline is a non-essential but still important amino acid that is released from enterocytes. Because plasma levels are reduced in case of impaired intestinal function, it has become a biomarker to monitor intestinal integrity. Moreover, oxidative stress induces protein citrullination, and antibodies against anti-citrullinated proteins are useful to monitor rheumatoid diseases.

Nutritional status, swallowing disorders, and respiratory prognosis in adult Duchenne muscular dystrophy patients.

Malnutrition and swallowing disorders are common in Duchenne muscular dystrophy (DMD) patients. We assessed, in adult DMD with home mechanical ventilation (HMV) and cough assist device, its prevalence and the relationships with respiratory muscle strength and long-term respiratory prognosis. We reviewed the patients (n = 117, age 18-39 years [median 24]), followed in a reference center, from 2006 to 2015, to obtain clinical baseline, nutritional status, vital capacity (VC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP).

Plasma citrulline correlates with basolateral amino acid transporter LAT4 expression in human small intestine.

Background & Aims: Plasma citrulline, a non-protein amino acid, is a biochemical marker of small intestine enterocyte mass in humans. Indeed, citrulline is highly correlated with residual bowel length in patients with short bowel syndrome. It is known to be synthesised in epithelial cells of the small intestine from other amino acids (precursors).

Diaphragm sniff ultrasound: Normal values, relationship with sniff nasal pressure and accuracy for predicting respiratory involvement in patients with neuromuscular disorders.

Background: In patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders.

Echographic Assessment of Diaphragmatic Function in Duchenne Muscular Dystrophy from Childhood to Adulthood.

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function.

Role of nutritional status in the early postoperative prognosis of patients operated for retroperitoneal liposarcoma (RLS): A single center experience.

Purpose: To assess the nutritional status and its role in the outcome of patients operated for retroperitoneal liposarcoma (RLS).

Material And Methods: Retrospective study on consecutive patients operated with en bloc compartment resection for primary or local recurrence of RLS between 2016 and 2017. Preoperative nutritional and laboratory assessment comprising serum albumin, serum transthyretin, orosomucoid, and CRP was systematically performed.

Feasibility and results of pull-percutaneous endoscopic gastrostomy for enteral nutrition in adults with severe cerebral palsy.

Background & Aims: Eating and swallowing impairments often get worse as patients with severe cerebral palsy (CP) get older, creating increased demand for percutaneous endoscopic gastrostomy (PEG) tube placement. Here we investigated the feasibility, safety, adverse events (AEs) and outcomes of PEG in adult CP.

Methods: We performed a retrospective study of 26 consecutive severe adult (age: 28 [19-48] yrs) CP patients who underwent pull-PEG tube placement under general anesthesia between 2005 and 2012 (median follow-up: 23 [6-64] months) at the same tertiary hospital centre.

Plasma L-citrulline concentrations and its relationship with inflammation at the onset of septic shock: a pilot study.

Purpose: Hypocitrullinemia has been suggested to be a prognostic factor for patients in intensive care. The aim of this ancillary study of the Corticosteroids and Intensive Insulin Therapy for Septic Shock prospective study was to investigate plasma L-citrulline concentrations and its relationship with inflammation and digestive bacterial translocation in patients with septic shock multiorgan failure and without primary intestinal disease or chronic renal failure.

Methods: Sixteen adult patients were selected.

Changes in weight after traumatic brain injury in adult patients: a longitudinal study.

Background & Aims: Although changes in weight have been reported after traumatic brain injury (TBI), their frequency and underlying factors are little known. Our aim was to determine the prevalence of weight changes and the associated factors during the recovery phase after TBI.

Methods: Longitudinal follow-up of adults with TBI.

Citrulline: from metabolism to therapeutic use.

Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver. The administration of citrulline may be used to deliver available nitrogen for protein homeostasis in peripheral tissues and as an arginine precursor synthesized de novo in the kidneys and endothelial and immune cells. Fresh research has shown that citrulline is efficiently transported across the intestinal luminal membrane by a set of transporters belonging to the B⁰,⁺, L, and b⁰,⁺ systems.

Hypertransaminasemia in severely malnourished adult anorexia nervosa patients: risk factors and evolution under enteral nutrition.

Background & Aims: Aminotransferase abnormalities have been reported in malnourished patients with anorexia nervosa (AN). The aim of this study was to identify prevalence and risk factors of hyperaminotransferasemia in an adult cohort of AN patients and to describe evolution during nutritional rehabilitation with enteral nutrition for a period of 4 weeks.

Methods: Retrospective study of all consecutive malnourished (BMI <16) AN adult patients, without previous liver diseases or hepatotoxic drugs or alcohol consumption, hospitalized for enteral nutrition in a single center between 1998 and 2008.

Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease.

The intestinal permeability of undegraded α9-gliadin peptide 31-49 (p31-49) and 33-mer gliadin peptides is increased in active celiac disease. Two distinct transport pathways have been proposed: paracellular leakage through epithelial tight junctions and protected transcellular transport. To analyze the relative contribution of these pathways, we compared mucosa-to-serosa permeability of small and large permeability markers [ionic conductance (G), mannitol, 182 Da; horseradish peroxidase, 40 kDa] and gliadin peptides [33-mer (p56-88, 3900 Da), 19-mer (p31-49, 2245 Da; and p202-220, 2127 Da), and 12-mer (p57-68, 1453 Da)] in duodenal biopsy specimens mounted in Ussing chambers.

[Circulating citrulline levels: a biomarker for intestinal functionality assessment].

Circulating citrulline is emerging as an innovating biomarker candidate for assessment of intestinal function. Amino acid synthesized by enterocytes of intestinal mucosal, citrulline is not included in proteins or nutrition products and is a precursor for production of arginine by the kidney. Plasma citrulline is, in clinical situation, an established biomarker of enterocyte functional metabolic mass (trophicity) in children and in adult patients due to its high relation to active functional small bowel remnant length in intestinal diseases (short bowel, extensive enteropathies, intestinal toxicity of chemotherapy and radiotherapy.

Effect of intestinal resections on arginine metabolism: practical implications for nutrition support.

Purpose Of Review: The present review relates recent developments in the understanding of arginine and citrulline metabolism and complementation after intestinal resection.

Recent Findings: Arginine metabolism is disturbed after significant intestinal resection, with reduced fluxes and circulating and tissue concentrations. There is also a reduction in citrulline production, a major source of endogenous arginine by enterocyte metabolism.

Plasma citrulline is a biomarker of enterocyte mass and an indicator of parenteral nutrition in HIV-infected patients.

Background: Plasma citrulline is a biomarker of enterocyte mass and function in humans.

Objective: We evaluated citrulline in the reemerging context of diarrhea in HIV-infected patients receiving highly active antiretroviral therapy.

Design: This study prospectively measured citrulline in 6 groups of HIV-1 patients (n = 115): 1) undetectable viral load without chronic diarrhea (a; n = 40) and with protease inhibitor-associated toxic chronic diarrhea (b; n = 26), 2) detectable viral load and CD4 > 200/mm(3) without (a; n = 6) and with (b; n = 11) chronic diarrhea, and 3) detectable viral load and CD4 <200/mm(3) without chronic diarrhea (a; n = 7) and with opportunistic intestinal infections or HIV enteropathy (b; n = 25).

Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction.

Background & Aims: In human, citrulline (plasma concentration about 40 micromol/L) is an amino acid involved in intermediary metabolism and that is not incorporated in proteins. Circulating citrulline is mainly produced by enterocytes of the small bowel. For this reason plasma or serum citrulline concentration has been proposed as a biomarker of remnant small bowel mass and function.

Citrulline and the gut.

Purpose Of Review: Citrulline, a nonprotein amino acid, is an important source of endogenous arginine. The gut is the main source of citrulline in humans. Hence, citrulline is a potential biomarker of short bowel function.

Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation.

We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation.

Hyperphagia contributes to the normal body composition and protein-energy balance in HIV-infected asymptomatic men.

Wasting can occur at an early stage of HIV infection. Both reduced energy intake and increased resting energy expenditure (REE) have been considered as factors in wasting with predominant lean body mass loss, suggesting disturbances of protein metabolism. Our aim was to study protein-energy metabolism in relation to body composition and oral energy intake in asymptomatic patients with HIV infection but receiving no active antiretroviral therapy.

Taurine kinetics assessed using [1,2-13C2]taurine in healthy adult humans.

To assess the dynamics of taurine metabolism in vivo, two sets of studies were carried out in healthy volunteers. First, pilot studies were carried in a single human subject to determine the time course of plasma and whole blood isotope enrichment over the course of an 8-h, unprimed continuous infusion of [1,2-(13)C(2)]taurine. Second, five healthy adult males received two tracer infusions on separate days and in randomized order: 1) a 6-h continuous infusion of [1,2-(13)C(2)]taurine (3.

Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease.

Background & Aims: Plasma citrulline, a nonprotein amino acid produced by enterocytes, was suggested as a marker of remnant enterocyte mass in patients with short bowel. Our objective was to evaluate citrulline as a marker of severity and extent of villous atrophy in patients without intestinal resection.

Methods: Forty-two patients with celiac disease and 10 patients with non-celiac villous atrophy disease were studied by plasma postabsorptive citrulline and biological dosages, biopsies of proximal (duodenojejunal) small bowel and distal ileum (n = 25), or measurement of vitamin B(12) absorption (n = 4).