scholarly journals Transplantation of bovine adrenocortical cells encapsulated in alginate

2015 ◽  
Vol 112 (8) ◽  
pp. 2527-2532 ◽  
Author(s):  
Mariya Balyura ◽  
Evgeny Gelfgat ◽  
Monika Ehrhart-Bornstein ◽  
Barbara Ludwig ◽  
Zohar Gendler ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Hpa Axis ◽  
Cell Biology ◽  
Treatment Options ◽  
Graft Function ◽  
3D Cell Culture ◽  
Normal Function ◽  
Acth Stimulation ◽  
Adrenocortical Cells ◽  
Tissue Organization

Current treatment options for adrenal insufficiency are limited to corticosteroid replacement therapies. However, hormone therapy does not replicate circadian rhythms and has unpleasant side effects especially due to the failure to restore normal function of the hypothalamic–pituitary–adrenal (HPA) axis. Adrenal cell transplantation and the restoration of HPA axis function would be a feasible and useful therapeutic strategy for patients with adrenal insufficiency. We created a bioartificial adrenal with 3D cell culture conditions by encapsulation of bovine adrenocortical cells (BACs) in alginate (enBACs). We found that, compared with BACs in monolayer culture, encapsulation in alginate significantly increased the life span of BACs. Encapsulation also improved significantly both the capacity of adrenal cells for stable, long-term basal hormone release as well as the response to pituitary adrenocorticotropic hormone (ACTH) and hypothalamic luteinizing hormone-releasing hormone (LHRH) agonist, [D-Trp6]LHRH. The enBACs were transplanted into adrenalectomized, immunodeficient, and immunocompetent rats. Animals received enBACs intraperitoneally, under the kidney capsule (free cells or cells encapsulated in alginate slabs) or s.c. enclosed in oxygenating and immunoisolating βAir devices. Graft function was confirmed by the presence of cortisol in the plasma of rats. Both types of grafted encapsulated cells, explanted after 21–25 d, preserved their morphology and functional response to ACTH stimulation. In conclusion, transplantation of a bioartificial adrenal with xenogeneic cells may be a treatment option for patients with adrenocortical insufficiency and other stress-related disorders. Furthermore, this model provides a microenvironment that ensures 3D cell–cell interactions as a unique tool to investigate new insights into cell biology, differentiation, tissue organization, and homeostasis.

Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis

2020 ◽  
Vol 33 (10) ◽  
pp. 1257-1263
Author(s):  
Justine Turmel-Roy ◽  
Marc-Antoine Bédard ◽  
Maude Millette ◽  
David Simonyan ◽  
Jean-Philippe Proulx-Gauthier ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Corticosteroid Injection ◽  
Significant Risk ◽  
Chronic Arthritis ◽  
Stimulation Test ◽  
Acth Stimulation ◽  
Common Procedure ◽  
Morning Cortisol ◽  
High Prevalence ◽  
Risks Factors

AbstractObjectivesIntra-articular and/or periarticular corticosteroid injection (IACI) is a common procedure in pediatric rheumatology. Despite many adult studies demonstrating a significant risk of adrenal insufficiency (AI) following the procedure, very little evidence is available in the pediatric literature regarding this risk. The main goal of this study is to evaluate the prevalence of AI in children with chronic arthritis following IACI.MethodsThis is a retrospective study including children aged 0-18 years who had an IACI from June 2017 to July 2019. An 8:00 morning cortisol (8MC) sample was drawn around two weeks after the injection, and an ACTH 1mcg stimulation test was performed if morning cortisol level was low. AI was defined as an 8MC under 50 nmol/L or an abnormal ACTH stimulation test. Risks factors for AI and its duration were assessed.ResultsSixty patients were included in this study. AI prevalence was 30% with 18 of 60 affected patients. The corticosteroid dose injected was statistically associated with the development of AI. Median duration of AI was 181 days for the nine patients who were followed up until resolution of AI. Four patients developed symptoms of AI, namely fatigue (2 of 4), nausea (2 of 4) and abdominal pain (3 of 4). None were hospitalized or died.ConclusionsIn this cohort of children with chronic arthritis who had an IACI, we found a high prevalence of AI. Monitoring and counseling of such complication is warranted until further evidence is available.

scholarly journals Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery?

2010 ◽  
Vol 162 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Cristina Eller-Vainicher ◽  
Valentina Morelli ◽  
Antonio Stefano Salcuni ◽  
Massimo Torlontano ◽  
Francesca Coletti ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Tolerance Test ◽  
Surgical Removal ◽  
Acth Stimulation ◽  
Unilateral Adrenalectomy ◽  
Free Cortisol ◽  
Few Data

ObjectiveFew data are available regarding the need of steroid substitutive therapy after unilateral adrenalectomy for adrenal incidentaloma (AI). It is unknown whether, before surgery, the hypothalamic–pituitary–adrenal (HPA) axis secretion parameters can predict post-surgical hypocortisolism.AimThis study aimed to evaluate whether, in AI patients undergoing unilateral adrenalectomy, post-surgical hypocortisolism could be predicted by the parameters of HPA axis function.DesignProspective, multicenter.MethodsA total of 60 patients underwent surgical removal of AI (surgical indication: 29 subclinical hypercortisolism (SH); 31 AI dimension). Before surgery, SH was diagnosed in patients presenting at least three criteria out of urinary free cortisol (UFC) levels>60 μg/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 μg/dl, ACTH levels<10 pg/ml, midnight serum cortisol (MSC)>5.4 μg/dl.Two months after surgery, HPA axis function was assessed by low dose ACTH stimulation test or insulin tolerance test when needed: 39 patients were affected (Group B) and 21 were not affected (Group A) with hypocortisolism. The accuracy in predicting hypocortisolism of pre-surgical HPA axis parameters or their combinations was evaluated.ResultsThe presence of >2 alterations among 1 mg-DST>5.0 μg/dl, ACTH<10 pg/ml, elevated UFC and MSC has the highest odds ratio (OR) for predicting post-surgical hypocortisolism (OR 10.45, 95% confidence interval, CI 2.54–42.95, P=0.001). Post-surgical hypocortisolism was predicted with 100% probability by elevated UFC plus MSC levels, but not ruled out even in the presence of the normality of all HPA axis parameters.ConclusionPost-surgical hypocortisolism cannot be pre-surgically ruled out. A steroid substitutive therapy is indicated after unilateral adrenalectomy for SH or size of the adenoma.

scholarly journals Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Beate Gündel ◽  
Xinyuan Liu ◽  
Matthias Löhr ◽  
Rainer Heuchel
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ex Vivo ◽  
Treatment Options ◽  
3D Cell Culture ◽  
Therapy Resistance ◽  
Ductal Adenocarcinoma ◽  
The Past ◽  
Slow Progress

Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.

scholarly journals 662 MICROVASCULAR MYOCUTANEOUS AND CUTANEOUS FREE FLAP RECONSTRUCTION FOR PATIENTS WITH TERMINAL ESOPHAGOSTOMY AFTER COMPLICATED ONCOLOGICAL ESOPHAGUS RESECTION

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Lukas Pölsler ◽  
Jaroslav Presl ◽  
Christian Brandtner ◽  
Alexander Gaggl ◽  
Jörg Hutter ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Free Flap ◽  
Treatment Options ◽  
Graft Function ◽  
Oral Intake ◽  
Artificial Nutrition ◽  
Severe Problem ◽  
Promising Alternative ◽  
Number Of Patients

Abstract   Persisting anastomotic leak after oncological esophagectomy is a severe problem associated with high mortality and morbidity. Unfortunately, treatment options with promising results are scarce especially when conventional operative and endoscopic methods have failed. Due to limitation of oral intake and need for artificial nutrition quality of life is reduced. Microvascular myocutaneous and cutaneous free flap (MFF) reconstruction could be a promising alternative. Methods This retrospective cohort study presents seven patients treated between March 2017 and November 2020 at our surgical department, with terminal esophagostomy after complicated oncological esophagus resection without further feasible treatment options. All Patients received anastomotic MFF reconstruction. We have examined postoperative outcomes, complications according to Clavien-Dindo-Classification and patient contentment with a questionnaire. Additionally, we described important procedure related facts. Results The included seven male patients had median age of 65.15 years (range: 48–75). MFF function was adequate in six out of seven patients, graft rejection appeared in one patient. Five patients initially had good results, surgical revision was performed in one patient to ensure graft function. Postoperative complications appeared in 6/7 patients (Table 1). Mean duration of inpatient care was 63 days (Range: 24–156). At time of evaluation, one patient has died cancer related. No more additional nutrition was needed in 3/6 patients with adequate graft function. The majority of patients reported an improved quality of life compared to preoperatively. Conclusion MFF free flap can be a safe and feasible treatment option for patients with terminal esophagostomy after complicated oncological esophagus resection without further treatment options or in patients with complicated postoperative course with complex combined defects. The renewed ability of oral food intake results in a significant improvement of quality of life for the patients. No procedure related mortality was observed. Number of patients with regained ability of oral intake is encouraging.

scholarly journals OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Amit Kumar ◽  
Maria Ghosh ◽  
Jubbin Jagan Jacob
Keyword(s):  
Adrenal Insufficiency ◽  
Hormone Secretion ◽  
Stimulation Test ◽  
Acth Stimulation Test ◽  
Sheehan’S Syndrome ◽  
Acth Stimulation ◽  
Steroid Use ◽  
Inappropriate Antidiuretic Hormone Secretion ◽  
Inhaled Steroids ◽  
Sheehan's Syndrome

Abstract Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) &lt;135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na &gt;30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of &lt;18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.

scholarly journals Actin Cytoskeleton Manipulation by Effector Proteins Secreted by DiarrheagenicEscherichia coliPathotypes

2013 ◽  
Vol 2013 ◽  
pp. 1-22 ◽  
Author(s):  
Fernando Navarro-Garcia ◽  
Antonio Serapio-Palacios ◽  
Paul Ugalde-Silva ◽  
Gabriela Tapia-Pastrana ◽  
Lucia Chavez-Dueñas
Keyword(s):  
Actin Cytoskeleton ◽  
Host Cell ◽  
Virulence Factors ◽  
Cell Biology ◽  
Bacterial Species ◽  
Effector Proteins ◽  
Actin Binding ◽  
E Coli ◽  
Tissue Organization ◽  
Epithelial Barriers

The actin cytoskeleton is a dynamic structure necessary for cell and tissue organization, including the maintenance of epithelial barriers. Disruption of the epithelial barrier coincides with alterations of the actin cytoskeleton in several disease states. These disruptions primarily affect the paracellular space, which is normally regulated by tight junctions. Thereby, the actin cytoskeleton is a common and recurring target of bacterial virulence factors. In order to manipulate the actin cytoskeleton, bacteria secrete and inject toxins and effectors to hijack the host cell machinery, which interferes with host-cell pathways and with a number of actin binding proteins. An interesting model to study actin manipulation by bacterial effectors isEscherichia colisince due to its genome plasticity it has acquired diverse genetic mobile elements, which allow having differentE. colivarieties in one bacterial species. TheseE. colipathotypes, including intracellular and extracellular bacteria, interact with epithelial cells, and their interactions depend on a specific combination of virulence factors. In this paper we focus onE. colieffectors that mimic host cell proteins to manipulate the actin cytoskeleton. The study of bacterial effector-cytoskeleton interaction will contribute not only to the comprehension of the molecular causes of infectious diseases but also to increase our knowledge of cell biology.

Perioperative Management of Patients on Steroids Requiring Surgery

2017 ◽  
Author(s):  
Alexandra Reiher ◽  
Rebecca S. Sippel ◽  
Dawn M. Elfenbein
Keyword(s):  
Adrenal Insufficiency ◽  
Hpa Axis ◽  
Hormone Secretion ◽  
Perioperative Period ◽  
Solid Organ ◽  
Glucocorticoid Treatment ◽  
Clinical Algorithm ◽  
Susceptibility To Infection ◽  
Inflammatory Bowel ◽  
Endogenous Steroid

Patients with chronic lung disease, inflammatory bowel disease, rheumatoid arthritis, and solid-organ transplantations are often on steroid supplementation either intermittently or chronically. Endogenous steroid use results in decreased adrenocorticotropic hormone secretion by the pituitary gland through negative feedback mechanisms. Over several weeks, this can result in adrenal gland atrophy, eventually leading to secondary adrenal insufficiency. Appropriate management of perioperative glucocorticoid replacement therapy can be challenging, but appropriate replacement is essential to optimize patient outcomes. Insufficient dosing of glucocorticoids during the perioperative period can result in hypotension and even death. Excessive treatment with glucocorticoids decreases wound healing, increases the risk of hyperglycemia, and increases susceptibility to infection. This review covers the historical perspective, the hypothalamic-pituitary-adrenal (HPA) axis, when to suspect an impaired HPA axis, an argument against supraphysiologic glucocorticoid treatment in the perioperative period, the rationale for treating patients with impaired renal function, guidelines for dosing glucocorticoids in the perioperative period, and consulting a specialist. Figures show a clinical algorithm for evaluation and treatment of adrenal insufficiency in the perioperative period and the HPA axis. Tables list steroid conversions and perioperative glucocorticoid treatment recommendations.   This review contains 2 highly rendered figures, 2 tables, and 22 references.

Thyroid Diseases

2019 ◽  
pp. 62-64
Author(s):  
Kevin B. Hoover
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Treatment Options ◽  
Normal Function ◽  
Thyroid Diseases ◽  
Hormone Levels ◽  
Musculoskeletal Manifestations ◽  
Hyperthyroid Patients ◽  
Serum Testing ◽  
Radioactive Iodine Ablation

Chapter 81 discusses thyroid diseases. Thyroid hormone is a regulator of normal physiology, including normal function of the musculoskeletal system. The most important causes of both elevated thyroid hormone levels (hyperthyroidism) and decreased hormone levels (hypothyroidism) are diseases of the thyroid gland. These are primarily diagnosed using serum testing and thyroid imaging. Muscle weakness is a common musculoskeletal complaint in both hyperthyroidism and hypothyroidism. In adults, osteoporosis is often evaluated in hyperthyroid patients using DXA, however, other musculoskeletal manifestations are often incidentally detected. Treatment options include radioactive iodine ablation of the thyroid gland, medical therapy, and surgery.

scholarly journals Multiscale mechanics of mucociliary clearance in the lung

2019 ◽  
Vol 375 (1792) ◽  
pp. 20190160 ◽  
Author(s):  
Janna C. Nawroth ◽  
Anne M. van der Does ◽  
Amy Ryan (Firth) ◽  
Eva Kanso
Keyword(s):  
Cell Biology ◽  
Mucociliary Clearance ◽  
Treatment Options ◽  
Diagnostic Tools ◽  
Regional Variability ◽  
Multiscale Mechanics ◽  
Airway Diseases ◽  
Open Questions ◽  
Human Lungs ◽  
The Relationship

Mucociliary clearance (MCC) is one of the most important defence mechanisms of the human respiratory system. Its failure is implicated in many chronic and debilitating airway diseases. However, due to the complexity of lung organization, we currently lack full understanding on the relationship between these regional differences in anatomy and biology and MCC functioning. For example, it is unknown whether the regional variability of airway geometry, cell biology and ciliary mechanics play a functional role in MCC. It therefore remains unclear whether the regional preference seen in some airway diseases could originate from local MCC dysfunction. Though great insights have been gained into the genetic basis of cilia ultrastructural defects in airway ciliopathies, the scaling to regional MCC function and subsequent clinical phenotype remains unpredictable. Understanding the multiscale mechanics of MCC would help elucidate genotype–phenotype relationships and enable better diagnostic tools and treatment options. Here, we review the hierarchical and variable organization of ciliated airway epithelium in human lungs and discuss how this organization relates to MCC function. We then discuss the relevancy of these structure–function relationships to current topics in lung disease research. Finally, we examine how state-of-the-art computational approaches can help address existing open questions. This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.

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