piperidines and Celiac-Disease

Topics: Aflatoxins; Africa; Age Factors; Aged; Alcohol Drinking; Anemia, Hypochromic; Anemia, Pernicious; Blood Group Antigens; Carcinogens; Celiac Disease; Esophageal Achalasia; Esophageal Neoplasms; Europe; Female; Gastrectomy; Humans; Japan; Keratosis; Male; Molybdenum; Nitrosamines; Nitroso Compounds; Piperidines; Plants; Precancerous Conditions; Sex Factors; Smoking; Stomach Neoplasms

Refractory coeliac disease (RCD) occurs when patients with confirmed CD have continuous or recurrent malabsorption and enteropathy after at least 12 months on a gluten-free diet. Differentiating between type I and type II RCD is key as the latter is associated with T-cell aberrancy and considered prelymphoma, with high mortality rates. Current treatment regimens for type II RCD include corticosteroids, biologics and chemotherapy, but there are no proven therapies for this serious condition. Our patient is a middle-aged woman who developed postpartum type II RCD. When she failed multiple drug classes, we did a trial of tofacitinib. Our clinical experience with use of a janus kinase inhibitor was successful, with no associated adverse events. This is the first report in the literature of RCD remission in response to tofacitinib. The use of this novel agent shows promise in reversing this potentially fatal condition.

Topics: Celiac Disease; Diagnosis, Differential; Diet, Gluten-Free; Female; Humans; Middle Aged; Piperidines; Pyrimidines; T-Lymphocytes

Dermatitis herpetiformis (DH) is a rare autoimmune blistering disorder in which patients with celiac disease, a gluten-sensitive enteropathy, present with a severely pruritic papulovesicular eruption over extensor surfaces such as the knees, elbows, lower back, buttocks, and neck. Patients are instructed to adhere to a gluten-free diet for purposes of improving their skin disease and gluten-sensitive enteropathy; this is the only treatment that lowers risk of enteropathy-associated T cell lymphoma. Patients who adhere to a strict gluten-free diet often have remission of their skin disease over months to years. Dapsone is a rapid and extremely effective first-line treatment option and often used while transitioning to a gluten-free diet. Aside from gluten-free diet and dapsone, second-line treatment options include sulfapyridine, sulfasalazine, and colchicine. Some patients have difficulty adhering to a gluten-free diet or develop intolerable side effects to systemic therapies. Furthermore, there is limited data on the use of the second-line treatments. Recent studies have shed light on the role of JAK-STAT-dependent pathways in the pathogenesis of dermatitis herpetiformis. We present a patient treated with tofacitinib, 5mg twice daily, an oral JAK1/3 inhibitor, who demonstrated clinical improvement of DH and control of new lesion development.

Topics: Aged; Celiac Disease; Dapsone; Dermatitis Herpetiformis; Diet, Gluten-Free; Drug Administration Schedule; Humans; Janus Kinase 1; Janus Kinase 3; Male; Patient Compliance; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Remission Induction; Treatment Outcome

Topics: Adolescent; Anti-Inflammatory Agents; Celiac Disease; Humans; Male; Piperidines; Pyrimidines; Remission Induction; Young Adult

Celiac disease (CD) is an immune-mediated, inflammatory disorder of the small intestines with a defined genetic etiological component associated with the expression of HLA-DQ2 and/or HLA-DQ8 haplotypes. The dietary consumption of gluten-rich cereals triggers a gluten-specific immune response in genetically susceptible individuals leading to a spectrum of clinical manifestations ranging from an inapparent subclinical disease, to overt enteropathy that can in some individuals progress to enteropathy-associated T cell lymphoma (EATL). The tissue-destructive pathologic process of CD is driven by activated NK-like intraepithelial CD8(+) lymphocytes and the proinflammatory cytokine IL-15 has emerged to be pivotal in orchestrating this perpetual tissue destruction and inflammation. Moreover, transgenic mice that over-express human IL-15 from an enterocyte-specific promoter (T3(b)-hIL-15 Tg) recapitulate many of the disease-defining T and B cell-mediated pathologic features of CD, further supporting the evolving consensus that IL-15 represents a valuable target in devising therapeutic interventions against the form of the disease that is especially refractory to gluten-free diet. In the present study, we evaluated the potential efficacy of tofacitinib, a pan-JAK inhibitor that abrogates IL-15 signaling, as a therapeutic modality against CD using T3(b)-hIL-15 Tg mice. We demonstrate that tofacitinib therapy leads to a lasting reversal of pathologic manifestations in the treated mice, thereby highlighting the potential value of tofacitininb as a therapeutic modality against refractory CD for which no effective therapy exists currently. Additionally, the visceral adiposity observed in the tofacitinib-treated mice underscores the importance of continued evaluation of the drug's impact on the lipid metabolism.

Topics: Animals; Celiac Disease; Disease Models, Animal; Female; Humans; Immunophenotyping; Interleukin-15; Intestine, Small; Janus Kinases; Killer Cells, Natural; Lymphocyte Subsets; Mice; Mice, Transgenic; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Spleen; Time Factors

Oral alimemazine and cisapride, or diazepam and cisapride, or iv midazolam and metoclopramide were given as premedication for small bowel biopsy to three groups of children from a total population of 185 individuals. The biopsy procedures were performed under intermittent fluoroscopy and times for both were recorded. The median biopsy procedure time was significantly shorter in children given iv midazolam and metoclopramide (6 min) compared to those given oral premedication (10 min) (p < 0.001). The median fluoroscopy time was very short in all groups, ranging between 3 and 6 s. It is concluded that iv premedication is superior to oral premedication for small bowel biopsy in children because more effective sedation is obtained.

Topics: Administration, Oral; Adolescent; Biopsy; Celiac Disease; Child; Child, Preschool; Cisapride; Diazepam; Fluoroscopy; Humans; Infant; Infusions, Intravenous; Intestine, Small; Metoclopramide; Midazolam; Piperidines; Premedication; Serotonin Antagonists; Trimeprazine

Urinary excretion of piperidine, a heterocyclic pressor amine of gut bacterial origin and nicotine-like activity in the brain, has been estimated by a gas chromatography method in healthy men and women, in normal breast-fed and formula-fed infants and in infants with untreated coeliac disease. The excretion of piperidine cannot usually be detected during the first week of life. The amount present in urine increases upon weaning with higher excretion in formula-fed than in breast-fed infants at four to six months of age. When premature infants fed on human milk are weaned, the urinary content of piperidine rises from undetectable amounts to normal for age. The high content present in untreated coeliac disease may be responsible for the initial mental depression commonly seen in this disease and suggests that piperidine is one of the "auto-intoxicating" substances arising from the bacterial decomposition of protein postulated by Metchnikoff in 1903 but hitherto unidentified.

Topics: Adult; Brain; Celiac Disease; Depression; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Intestine, Small; Male; Milk Proteins; Piperidines

Topics: Amines; Anaerobiosis; Animals; Bacteria; Bile Acids and Salts; Blind Loop Syndrome; Celiac Disease; Female; Growth; Hippurates; Indican; Indoleacetic Acids; Intestine, Small; Lincomycin; Malabsorption Syndromes; Neomycin; Phenols; Piperidines; Proteins; Pyrrolidines; Rats

Topics: Celiac Disease; Cyanides; Digestion; Growth; Intestine, Small; Intestines; Lipid Metabolism; Minerals; Piperidines; Rats; Research; Sprue, Tropical; Surgical Procedures, Operative; Tooth