Rafael Frias

Karolinska Institutet | KI · Komparativ medicin

Intestinal permeability (IP) tests are used to assess intestinal damage in patients and research models. The probe iohexol has shown advantages compared to 51Cr-EDTA or absorbable/nonabsorbable sugars. During IP tests, animals are housed in metabolic cages (MCs) to collect urine. We examined the performance of an iohexol IP test in mice. Rag1-/- (C...

Background Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species. Methods Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of i...

Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemoth...

Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection ca...

Iohexol is a non-radioactive, iodinated, water-soluble radiographic contrast medium that is widely used in detection imaging for both clinical and scientific purposes. It has also been used as a marker for glomerular filtration rate (GFR) and intestinal permeability (IP) in both humans and animals, such as dogs, rats and cats. Currently, iohexol is...

Purpose: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT i...

Previous studies using a BALB/cOlaHsd model have shown the impact that the supplementation of infant formula with polyamines has on the modulation of microbial colonization and immune system development. To contribute to deciphering and identifying new complex interactions underlying the host response to polyamines, a systems biology approach integ...

Coeliac disease is hallmarked by an abnormal immune reaction against ingested wheat-, rye- and barley-derived gluten and the presence of transglutaminase 2 (TG2)-targeted autoantibodies. The small-bowel mucosal damage characteristic of the disorder develops gradually from normal villus morphology to inflammation and finally to villus atrophy with c...

Purpose: Gastrointestinal toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity...

Unlabelled: Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be pas...

The aim of this work was to study whether the proportion of polyamine found in human milk, administered with a commercial infant formula, affected the maturation of the immune system in a BALB/cOlaHsd mouse model. Forty-eight pups (14-days old) were randomly assigned to four-day intervention groups: 1) breast-fed (normal lactation); 2) fed infant f...

Introduction: Disturbances of the gut barrier function have been related to a variety of diseases, including intestinal and extra-intestinal diseases. The intestinal permeability tests are considered useful tools for evaluating disease severity and to follow-up patients after a therapeutic intervention and indirectly assess barrier function. Obje...

Collecting milk samples from mice (Mus musculus) may be interesting for a variety of preclinical research. References in the literature for protocols describing how to milk a dam are scarce, and a major limitation of such protocols is the small sample volume that is generally collected. The aim of our study was to develop a practical protocol to co...

Assessment of intestinal damage in laboratory rats with experimentally-induced enteropathies is usually carried out by collecting and morphological interpreting tissue samples obtained surgically, endoscopically or at necropsy. Alternatively, changes in the gut mucosa may be less invasively evaluated with intestinal permeability (IP) tests. In cont...

Infant microbiota is influenced by numerous factors, such as delivery mode, environment, prematurity and diet (breast milk or formula). In addition to its nutritional value, breast milk contains bioactive substances that drive microbial colonisation and support immune system development, which are usually not present in infant formulas. Among these...

Background and objectives: The development of the human microbiome is a complex process, which may begin during the perinatal period when the infant is exposed to the mother’s microbiota. Feeding practices (breast milk or formula) influence the establishment of microbiota, which is known to play an essential role for the maturation of the immune sy...

A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify t...

Three-dimensional endothelial cell tubule formation assay. Several angiogenic parameters quantified from human umbilical vein endothelial cells cultured inside matrigel for 48 h without any supplementation (basal) or in the presence of celiac patient-derived total IgA (CD IgA) or monoclonal antibodies (CD Mab), or their relevant controls (non-CD Ig...

The percentage of apoptotic cells in the presence of celiac antibodies Apoptotic human umbilical vein endothelial cells inside matrigel cultures without any supplementation (basal) or in the presence of celiac patient-derived total IgA (CD IgA) or its respective control (non-CD IgA), or monoclonal celiac or control antibodies (CD Mab or non-CD Mab,...

Tubule dynamics of endothelial cells supplemented with celiac or control antibodies. Human umbilical vein endothelial cells were grown inside matrigel in the presence of celiac patient-derived total IgA (CD IgA) or monoclonal antibodies (CD Mab), or their relevant controls (non-CD IgA or non-CD Mab) for ten days in a Cell-IQ system. During the assa...

Positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) scanning 3D video from a mouse with matrigel implants. PET and PET/CT scanning video of a mouse with matrigel implants without any supplementation (basal) or supplemented with celiac disease-specific transglutaminase 2-targeted monoclonal autoantibodies...

Objective —To provide values for gastrointestinal permeability and absorptive function tests (GIPFTs) with chromium 51 ( ⁵¹ Cr)-labeled EDTA, lactulose, rhamnose, d -xylose, 3-O-methyl- d -glucose, and sucrose in Beagles and to evaluate potential correlations between markers. Animals —19 healthy adult male Beagles. Procedures —A test solution conta...

(51)Chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) is the gold standard probe for assessing intestinal permeability (IP) in dogs, but exposure to radioactivity is a disadvantage. Iohexol is a safe contrast medium commonly used for medical imaging purposes and has been successfully applied more recently for the assessment of IP in...

A 51-chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) permeability blood test was validated as a method to assess damage to the small intestine in dogs. The test was performed by calculating various percentages from sera after an orally ingested dose solution. The aim of the current study was to determine whether the use of serum or...

Permanent jejunal fistulas enable easy, noninjurious, repeated and direct administration to and collection from the small intestines of conscious laboratory dogs. This study aimed at identifying potential alterations in the small intestinal morphology and function of this canine model after the surgery required to establish the fistulas. Assays of...

Objectives and Study: Polyamines are organic compounds present in the human milk. Besides their nutritional role, polyamines are known to play a key role in the development of infant immune system during lactation. In general, the amount of polyamines included in infant formulas (IF) is around ten-fold less than in breast milk. The aim of this stud...

A rapid high-performance liquid chromatography UV method and a simple sample preparation for analyzing iohexol in canine plasma, for evaluating glomerular filtration rate (GFR) and intestinal permeability, were developed and validated. Trifluoroacetic acid (TFA) was used for protein precipitation and iohexol extraction from plasma, followed by vort...

Lactobacillus rhamnosus is one of the most widely used probiotic microorganisms. Although this microorganism is not known for its virulence some rare cases of bacteraemia and endocarditis have been observed. Thus, it is important to identify the possible risks associated with each strain. Comparison of clinical and probiotic strains may give inform...

Iohexol is a nonradioactive marker that has been used successfully to test intestinal permeability in humans with inflammatory bowel disease. There is evidence in dogs that iohexol shares a similar permeability pathway as (51)chromium-EDTA, the gold standard marker. The objective of this study was to determine an optimal oral iohexol dosage for an...

Viable microbes have been a natural part of human diet throughout the history of mankind. Today, different fermented foods and other foods containing live microbes are consumed around the world, including industrialized countries, where the diet has become increasingly sterile during the last decades. By definition, probiotics are viable microbes w...

Lactic acid bacteria have long been used to improve the safety of foods through fermentation. Some fermented products were also early used for their perceived health benefits, which lead to the development of probiotics as we now know them. Probiotics mainly belong to the genera Lactobacillus and Bifidobacterium. Most members of these genera are no...

Seven beagles in a colony of dogs had chronic diarrhea for at least 30 days. The dogs were subsequently treated with tylosin 20 mg/kg BW q24h PO for 10 days. During the treatment period, the feces became firmer but remained loose. When the treatment was discontinued, the diarrhea reappeared in 3 weeks. The feces remained abnormally loose in all dog...

The 51Cr-EDTA test is a valuable clinical tool for screening intestinal diseases in dogs. The test is performed by calculating the percentage of recovery from urine of a PO-ingested dose of 51Cr-EDTA after 6 or 24 hours. Careful urine collection is a practical limitation of this test in dogs, and our goal was to develop a simpler test that measures...

Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant beta-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing amp...