scholarly journals Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology

2015 ◽  
Vol 308 (6) ◽  
pp. G459-G471 ◽  
Author(s):  
Alicia K. Olivier ◽  
Katherine N. Gibson-Corley ◽  
David K. Meyerholz
Keyword(s):  
Cystic Fibrosis ◽  
Gastrointestinal Tract ◽  
Animal Models ◽  
Liver Diseases ◽  
Multiple Organ ◽  
Hepatobiliary Disease ◽  
Future Directions ◽  
Organ Systems

Multiple organ systems, including the gastrointestinal tract, pancreas, and hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these changes begin early in life and are difficult to study in young CF patients. Recent development of novel CF animal models has expanded opportunities in the field to better understand CF pathogenesis and evaluate traditional and innovative therapeutics. In this review, we discuss manifestations of CF disease in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal models. We also compare the similarities and limitations of animal models and discuss future directions for modeling CF.

Management of the Child With Cystic Fibrosis

1996 ◽  
Vol 9 (1) ◽  
pp. 75-90
Author(s):  
Jennifer H. Tran ◽  
Karen M. Brennan
Keyword(s):  
Cystic Fibrosis ◽  
Gastrointestinal Tract ◽  
Neonatal Period ◽  
Pancreatic Insufficiency ◽  
Childhood Illness ◽  
Serum Concentrations ◽  
Enzyme Replacement ◽  
Organ Systems ◽  
Made In

Cystic fibrosis is one of the most common lethal inherited diseases among the Caucasian population, with an incidence of 1 in 2,000. With the progress made in the management of the disease, a once-regarded childhood illness has now an improved survival rate of up to 30 years. It is a multifaceted disease affecting a number of organ systems primarily pulmonary and gastrointestinal tract, with the former leading to most of the mortality. Therefore, good pulmonary toilet, including daily chest physiotherapy and appropriate antibiotic treatment for acute pulmonary exacerbations, remains the cornerstone of therapy. Disease-specific pharmacokinetics seen in these patients require special dosing considerations specifically for antibiotics to ensure adequate serum concentrations. In addition, bronchodilators, steroids, and mucolytics also play a role. With respect to the gastrointestinal tract, pancreatic insufficiency occurs and requires enzyme replacement. Intestinal obstruction may occur as early as the neonatal period, as "meconium ileus," and recur throughout the patient's lifespan. More recent modalities including chloride-channel facilitators, antiproteases, and gene therapy may hold promise to further improve the survival and quality of life in these individuals. The pharmacists' role is vital, especially with the unique pharmacokinetic considerations specific to this population and the complexity of medications necessary for appropriate management of the disease. Copyright © 1996 by W.B. Saunders Company

scholarly journals Toll like Receptor signalling by Prevotella histicola activates alternative NF-κB signalling in Cystic Fibrosis bronchial epithelial cells compared to P.aeruginosa

2020 ◽  
Author(s):  
A. Bertelsen ◽  
J.S. Elborn ◽  
B.C. Schock
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Multiple Organ ◽  
Bronchial Epithelial Cells ◽  
Toll Like Receptor ◽  
Bronchial Epithelial ◽  
Hek 293 ◽  
Organ Systems

AbstractCystic Fibrosis (CF), caused by mutations affecting the CFTR gene, is characterised by viscid secretions in multiple organ systems. CF airways contain thick mucus, creating a gradient of hypoxia, which promotes the establishment of polymicrobial infection. Such inflammation predisposes to further infection, a self-perpetuating cycle in mediated by NF-κB. Anaerobic Gram-negative Prevotella spp. are found in sputum from healthy volunteers and CF patients and in CF lungs correlate with reduced levels of inflammation. Prevotella histicola (P.histicola) can suppress murine lung inflammation, however, no studies have examined the role of P.histicola in modulating infection and inflammation in the CF airways. We investigated innate immune signalling and NF-kB activation in CF epithelial cells CFBE41o-in response to clinical stains of P.histicola and Pseudomonas aeruginosa (P.aeruginosa). Toll-Like Receptor (TLR) expressing HEK-293 cells and siRNA assays for TLRs and IKKa were used to confirm signalling pathways.We show that P.histicola infection activated the alternative NF-kB signalling pathway in CF bronchial epithelial cells inducing HIF-1α protein. TLR5 signalling was responsible for the induction of the alternative NF-kB pathway through phosphorylation of IKKα. The induction of transcription factor HIF-1α was inversely associated with the induction of the alternative NF-kB pathway and knockdown of IKKα partially restored canonical NF-kB activation in response to P.histicola.This study demonstrates that different bacterial species in the respiratory microbiome can contribute differently to inflammation, either by activating inflammatory cascades (P.aeruginosa) or by muting the inflammatory response by modulating similar or related pathways (P.histicola). Further work is required to assess the complex interactions of the lung microbiome in response to mixed bacterial infections and their effects in people with CF.

scholarly journals Management of tracheo-oesophageal fistula in adults

2020 ◽  
Vol 29 (158) ◽  
pp. 200094
Author(s):  
Hyun S. Kim ◽  
Danai Khemasuwan ◽  
Javier Diaz-Mendoza ◽  
Atul C. Mehta
Keyword(s):  
Clinical Manifestations ◽  
Therapeutic Strategies ◽  
Multiple Organ ◽  
Future Directions ◽  
Airway Stent ◽  
Organ Systems ◽  
Diagnostic Approaches ◽  
3D Printed ◽  
Stenting Procedure ◽  
Traumatic Damage

Tracheo-oesophageal fistula (TOF) is a pathological connection between the trachea and the oesophagus that is associated with various underlying conditions including malignancies, infections, inhalation injuries and traumatic damage. As the condition spans multiple organ systems with varying aetiologies and acuities, TOF poses unique diagnostic and management challenges to pulmonologists, gastroenterologists and thoracic surgeons alike. Although stents have been a cornerstone in the management of TOF, there exists a large gap in our understanding of their efficacy and precise methodology, making stenting procedure both art and science. TOFs relating to underlying oesophageal or tracheal malignancies require advanced understanding of the airway and digestive tract anatomy, dimensions of the fistula, stent characteristics and types, and the interplay between the oesophageal stent and the airway stent if dual stenting procedure is elected. In this review article, we review the most up-to-date data on risk factors, clinical manifestations, diagnostic approaches, management methods and prognosis. Consequently, this article serves to evaluate current therapeutic strategies and the future directions in the areas of 3D-printed stents, over-the-scope clipping systems, tissue matrices and atrial septal closure devices.

scholarly journals Beyond the Gastrointestinal Tract: The Emerging and Diverse Tissue Tropisms of Astroviruses

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 732
Author(s):  
Andrew B. Janowski
Keyword(s):  
Gastrointestinal Tract ◽  
Respiratory Tract ◽  
Causal Relationship ◽  
Rna Viruses ◽  
Neurological Diseases ◽  
Multiple Organ ◽  
Organ Systems ◽  
Positive Sense ◽  
Localized Disease ◽  
Tissue Tropisms

Astroviruses are single stranded, positive-sense RNA viruses that have been historically associated with diseases of the gastrointestinal tract of vertebrates, including humans. However, there is now a multitude of evidence demonstrating the capacity of these viruses to cause extraintestinal diseases. The most striking causal relationship is neurological diseases in humans, cattle, pigs, and other mammals, caused by astrovirus infection. Astroviruses have also been associated with disseminated infections, localized disease of the liver or kidneys, and there is increasing evidence suggesting a potential tropism to the respiratory tract. This review will discuss the current understanding of the tissue tropisms for astroviruses and their emerging capacity to cause disease in multiple organ systems.

scholarly journals Perioperative Management and Preemptive ECMO Cannulation of a Parturient with Cystic Fibrosis Undergoing Cesarean Delivery

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Thais Franklin Dos Santos ◽  
Andrea Rabassa ◽  
Oscar Aljure ◽  
Reine Zbeidy
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Failure ◽  
Cesarean Delivery ◽  
Perioperative Management ◽  
Pancreatic Insufficiency ◽  
Multiple Organ ◽  
Organ Systems ◽  
Cardiac Manifestations ◽  
Poor Nutrition ◽  
Physiologic Changes Of Pregnancy

Physiologic changes of pregnancy and cystic fibrosis pathology provide a unique set of circumstances. Pulmonary disease accounts for over 90% of the morbidity and mortality of patients with cystic fibrosis. These abnormalities create anesthetic challenges due to multiple organ systems being affected including the respiratory, gastrointestinal, cardiovascular, and genitourinary tracts, where patients present with chronic respiratory failure, pancreatic insufficiency, poor nutrition, and cardiac manifestations. We present the perianesthetic management of a parturient with cystic fibrosis who successfully underwent preterm cesarean delivery under neuraxial anesthesia with preemptive bilateral femoral venous sheaths placed for potential extracorporeal membrane oxygenation (ECMO) initiation.

scholarly journals Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent.

1997 ◽  
Vol 8 (2) ◽  
pp. 352-355
Author(s):  
C M Bates ◽  
M Baum ◽  
R Quigley
Keyword(s):  
Cystic Fibrosis ◽  
Metabolic Alkalosis ◽  
Extracellular Fluid ◽  
Multiple Organ ◽  
Healthy Adolescent ◽  
Volume Contraction ◽  
Warm Weather ◽  
Organ Systems ◽  
Cystic Fibrosis Transmembrane ◽  
Sweat Sodium

Cystic fibrosis (CF) is an exocrine disease affecting multiple organ systems. Patients with CF usually present with respiratory or gastrointestinal abnormalities. This study presents a case of a previously healthy 17-yr-old man who was diagnosed with CF after presenting with metabolic alkalosis and hypokalemia. The defect associated with CF is in the cystic fibrosis transmembrane regulator (CFTR), which acts primarily as a chloride channel. Partially functional CFTR may be associated with less severe pulmonary and gastrointestinal manifestations, as in the case presented. Dysfunctional CFTR in the sweat ducts of CF patients are responsible for excessive chloride and sodium losses, especially in warm weather. Hypokalemia seen with heat stress is secondary to sweat as well as renal potassium wasting. Metabolic alkalosis is maintained by the excessive sweat sodium chloride losses which leads to extracellular fluid (ECF) volume contraction and chloride depletion. Generation of alkalosis may be related to dysfunctional CFTR in the kidney, but is most likely secondary to hypokalemia with ECF volume contraction. Finally, one must consider CF when confronted with hypokalemia and alkalosis in a previously healthy patient.

Cystic fibrosis and caseload midwifery

2021 ◽  
Vol 29 (12) ◽  
pp. 712-717
Author(s):  
Sophie Borges
Keyword(s):  
Cystic Fibrosis ◽  
Multiple Organ ◽  
Holistic Care ◽  
Health And Wellbeing ◽  
Caseload Midwifery ◽  
Organ Systems ◽  
Psychosocial Implications ◽  
Small Team ◽  
Improve Health ◽  
Made In

Midwives must provide woman-centred, holistic care for the diverse UK childbearing population. As the NHS moves to adopt the recommendations made in the ‘Better Births’ report, is there an argument to invest in protected caseload midwifery contacts for women with cystic fibrosis? Caseload midwifery refers to a continuity model where a small team of midwives provide care throughout the antenatal, intrapartum and postnatal continuum. Cystic fibrosis affects multiple organ systems and requires specialist medical management during pregnancy. Living with cystic fibrosis has many psychosocial implications and pregnancy presents additional challenges. Health and wellbeing outcomes are improved when individuals are treated holistically in the non-pregnant population; therefore, during pregnancy, birth and postnatally, caseload midwifery may provide a legitimate intervention to improve health outcomes in pregnant women with cystic fibrosis.

Cystic fibrosis - general review on sinonasal complications and case report

2017 ◽  
Vol 7 (25) ◽  
pp. 33-37
Author(s):  
Claudiu Manea ◽  
Alina Diaconescu
Keyword(s):  
Quality Of Life ◽  
Cystic Fibrosis ◽  
Case Report ◽  
Life Expectancy ◽  
Multiple Organ ◽  
Lower Airway ◽  
General Review ◽  
Organ Systems ◽  
Sinonasal Disease

Abstract An irreversible disease, cystic fibrosis (CF), is responsible for affecting multiple organ systems containing epithelia. It is well known that the sinonasal disease caused by CF has consequences for the incidence of the lower airway exacerbations, as well as affecting the quality of life of those patients. This review provides an update by evaluating the available literature regarding pathogenesis, management and treatment of cystic fibrosis patients. To gain a better view of the disease and obtain a higher life expectancy, further studies are needed.

scholarly journals Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Filipe Palavra ◽  
Conceição Robalo ◽  
Flávio Reis
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Inhibitors ◽  
Multiple Organ ◽  
Future Directions ◽  
Cell Functions ◽  
Organ Systems ◽  
Tumor Like Lesions ◽  
Mtor Signalling

Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of benign, noninvasive, and tumor-like lesions called hamartomas that can affect multiple organ systems and are responsible for the clinical features of the disease. In the majority of cases, TSC results from mutations in the TSC1 and TSC2 genes, leading to the overactivation of the mammalian target of rapamycin (mTOR) signalling pathway, which controls several cell functions, including cell growth, proliferation, and survival. The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. However, the intrinsic characteristics of these drugs and their systemic effects in such a heterogeneous condition pose many challenges in clinical practice, so that some questions remain unanswered. This article provides an overview of the pharmacological aspects of mTOR inhibitors about the clinical trials leading to their approval in TSC-related conditions and exposes current challenges and future directions associated with this promising therapeutic line.

scholarly journals Multi-Organ System Dysfunction in Covid-19 – A Review

2021 ◽  
Vol 10 (9) ◽  
pp. 632-637
Author(s):  
Pooja Bhadoria ◽  
Harsha Rathore
Keyword(s):  
Nervous System ◽  
Gastrointestinal Tract ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Wide Distribution ◽  
Multiple Organ ◽  
Organ System ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Organ Systems

With a continuous increase in Covid-19 cases, patients infected with SARS-CoV-2 have shown a wide variety of symptoms including fever, shortness of breath, cough, myalgia, dizziness, headache, impaired consciousness, abdominal pain and diarrhoea. Lab studies have shown higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), decreased lymphocytes, increased prothrombin time and a partial thromboplastin time, increased serum lactate dehydrogenase, ferritin and various other markers, indicating multiple organ system dysfunction including respiratory system, immune system, nervous system and gastrointestinal tract. Apart from these, heart and kidneys are also found to be affected in some patients. Patients presenting with previous history of diseases such as cardiovascular diseases, kidney diseases, pregnant females, neonates, immunosuppressed patients, and aged people have shown poor prognosis of disease. Various studies suggest possible reasons of multiple organ dysfunctions including wide distribution of angiotensin-converting enzyme 2 (ACE-2) receptors, cytokine storm and hypercoagulability of blood. We have listed the various organ systems affected by the virus and possible explanations as to why and how these organ systems are affected. SARS-CoV-2 outbreak has caused a global pandemic, with more than 33,400,000 confirmed cases of Covid-19, including more than 1,000,000 deaths, reported to World Health Organization (WHO) globally till 30 September 2020. 1 with a basic reproductive number estimated to be 2.2 (1.4 - 3.9) the virus spread is very fast affecting many individuals across the globe. 2 One of the major causes of efficient spread of SARS-CoV-2 in humans is the angiotensin-converting enzyme 2 receptors, used by the virus to enter the cells. 3 Hence, wide distribution of angiotensin-converting enzyme 2 receptors in body including lungs, kidney, bladder, gastrointestinal tract, heart, central nervous system and peripheral nervous system4 and even placenta5 is one of the reasons the virus is found to affect these organs. Two closely related viruses causing Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) were also found to affect multiple organ systems. SARS‐CoV-1 was found in the respiratory pathway (trachea, bronchus, lung), gastrointestinal tract (stomach, small intestines), glands (sweat gland, liver, pancreas, parathyroid, pituitary, adrenal gland), renal system (convoluted renal tubules) and brain tissue (cerebrum) in the autopsy samples of patients who died because of severe acute respiratory syndrome. 6 Respiratory, circulatory, gastrointestinal, haematological, renal and hepatological symptoms were also found to be affected in patients with Middle East respiratory syndrome infection. 7 Though the virus is found to affect multiple organ systems, the underlying mechanisms are not clearly understood.

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