Paneth cell defensins: key effector molecules of innate immunity

2006 ◽  
Vol 34 (2) ◽  
pp. 263-266 ◽  
Author(s):  
C.L. Bevins
Keyword(s):  
Innate Immunity ◽  
Paneth Cell ◽  
Intestinal Wall ◽  
Intestinal Lumen ◽  
Murine Models ◽  
Key Factors ◽  
Effector Molecules ◽  
Wide Range ◽  
Key Factor ◽  
Inflammatory Bowel

Antimicrobial peptides are fundamental effector molecules of innate immunity, utilized in host defence by virtually all organisms studied. These gene-encoded peptides have direct antibiotic activity against a wide range of bacteria and other microbes. In humans and other mammals, defensins are a predominant class of such peptides. In the mammalian small intestine, Paneth cells, specialized secretory epithelial cells located at the base of the crypt invaginations lining the intestinal wall, produce defensins and other antibiotic proteins. Recent investigations in murine models provide compelling support for the hypothesis that enteric defensins play a pivotal role in defence from food- and water-borne pathogens in the intestinal lumen. Investigations by others indicate that intestinal commensal bacteria are key factors in the pathogenesis of IBD (inflammatory bowel disease) in genetically susceptible humans. Recent studies provide evidence that reduced expression of Paneth cell defensins may be a key factor in the pathogenesis of ileal Crohn's disease, a subgroup of IBD. Future studies to further define the function and regulation of Paneth cell defensins will enhance our understanding of normal small bowel physiology, and probably contribute to a better understanding of the pathogenesis of inflammatory and infectious diseases of the bowel. Such knowledge may provide new therapeutic targets and strategies.

Events at the Host-Microbial Interface of the Gastrointestinal Tract V. Paneth cell α-defensins in intestinal host defense

2005 ◽  
Vol 289 (2) ◽  
pp. G173-G176 ◽  
Author(s):  
Charles L. Bevins
Keyword(s):  
Small Intestine ◽  
Host Defense ◽  
Paneth Cell ◽  
Intestinal Wall ◽  
Chronic Inflammatory Bowel Disease ◽  
Cationic Peptides ◽  
Wide Range ◽  
Inflammatory Bowel ◽  
Chronic Inflammatory Bowel

Host defense of the small intestine is mediated, in part, by antimicrobial peptides, including α-defensins. In the small intestine, Paneth cells, specialized secretory epithelial cells located at the base of the crypt invaginations lining the intestinal wall, produce α-defensins. The α-defensins are cysteine-rich cationic peptides with antibiotic activity against a wide range of bacteria and other microbes. Studies of transgenic and knockout mice have supported a pivotal role of Paneth cell α-defensins in protection from bacterial pathogens. New data suggest that deficient expression of Paneth cell α-defensins may contribute to the pathophysiology of Crohn's disease, a chronic inflammatory bowel disease.

scholarly journals Primary exudative enteropathy: a clinical case

2021 ◽  
Vol 2 (2) ◽  
pp. 88-93
Author(s):  
I. Yu. Statsenko ◽  
O. Yu. Sviridenko ◽  
R. G. Myazin ◽  
D. N. Emelyanov ◽  
A. O. Sviridenko
Keyword(s):  
Plasma Proteins ◽  
Lymphatic Vessel ◽  
Clinical Case ◽  
Intestinal Wall ◽  
Clinical Syndrome ◽  
Lymph Flow ◽  
Intestinal Lumen ◽  
Resistance To Therapy ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Primary exudative enteropathy is a rare disease caused by the formation of lymphatic vessel abnormalities in the intestinal wall, the development of pathological lymph flow into the intestinal lumen, and increased loss of plasma proteins in the feces. The leading clinical syndrome of the disease is edema with the development of hypoalbuminemia and dysproteinemia. To establish the diagnosis, it took numerous studies with the exception of the patient’s pathology of the kidneys, liver, and inflammatory bowel diseases. The course of the disease was characterized by significant resistance to therapy.

Defensins and cathelicidins in inflammatory lung disease: beyond antimicrobial activity

2006 ◽  
Vol 34 (2) ◽  
pp. 276-278 ◽  
Author(s):  
P.S. Hiemstra
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Wound Repair ◽  
First Line ◽  
Gram Negative ◽  
Enveloped Viruses ◽  
Effector Molecules ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Micro Organisms

Innate immunity provides an effective first line of defence against infections. This is of particular importance in the lung, an organ that is exposed to a large number of pathogens that are inhaled. Antimicrobial peptides play an important role in the defence against these pathogens as effector molecules of innate immunity. These peptides are mainly produced by phagocytes and epithelial cells, and kill a wide range of micro-organisms: Gram-negative and Gram-positive bacteria, fungi and (enveloped) viruses. However, it is increasingly evident that these peptides not only act as endogenous antibiotics, but also display a range of other functions, including activities that are involved in regulating immune responses and inflammation, and wound repair. In this review, these activities are highlighted and their role in inflammatory lung disorders is discussed.

scholarly journals Clinical, Ultrasonographic and Histopathological Findings of Gastrointestinal Disorders in Cats

2018 ◽  
Vol 46 (1) ◽  
pp. 6
Author(s):  
Cristiane Aguero Da Silva ◽  
Simone Carvalhos dos Santos Cunha ◽  
Heloisa Justen Moreira De Souza ◽  
Amanda Chaves De Jesus ◽  
Ana Maria Reis Ferreira
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mast Cell ◽  
Wall Thickness ◽  
Bowel Disease ◽  
Clinical Signs ◽  
Intestinal Wall ◽  
Cell Tumor ◽  
Intestinal Lumen ◽  
Mast Cell Tumor ◽  
Inflammatory Bowel

Background: Gastrointestinal disorders are common in cats, and the differentiation between inflammatory and neoplastic disease is essential to determine therapy. Therefore, ultrasonographic evaluation is an important tool for intestinal diagnosis in cats. The aim of this study is to evaluate the clinical, ultrasonographic and histopathological characteristics of cats with intestinal diseases.Materials, Methods & Results: Forty cats with gastrointestinal clinical signs and abdominal ultrasound findings consistent with inflammatory bowel disease or gastrointestinal neoplasia were studied. Ultrasound evaluated all abdominal organs, with emphasis on the gastrointestinal tract, and parameters included the thickness of gastric and intestinal wall, the variations of its echogenicity, reduced intestinal lumen, mesenteric lymph nodes, involvement of other abdominal organs and presence of abdominal effusion. All cats were referred to exploratory laparotomy, in order to obtain biopsy samples. Mean age was 11.6 years and there were 23 females and 17 males. Clinical signs included weight loss (87.5%), vomiting (82.5%), hyporexia (75%), diarrhea (35%), constipation (10%), polyphagia (5%) and intestinal gases (5%). In abdominal ultrasound, the most common findings were increased thickness of the gastric and/or intestinal wall, decreased echogenicity of the intestinal wall, reduction of the intestinal lumen due to severe wall thickening or presence of obstructive mass, and lymphadenopathy. Histopathology revealed alimentary lymphoma (AL) in 19 cases, inflammatory bowel disease (IBD) in 10 cases, intestinal adenocarcinoma in 7 cases, mast cell tumor in 2 cases and intestinal hemangiosarcoma in 2 cases.Discussion: Weight loss and vomiting were the two main complaints of the owners. However, diarrhea, described by previous authors as one of the main clinical signs in cats with intestinal diseases, was present in only 35% of cats of this study. The intestinal segments that were presented more frequently with increased wall thickness were duodenum and jejunum, and the mean wall thickness was 0.51 cm. Cats diagnosed with AL had mean value of duodenum wall thickness/jejunum of 0.564 cm, while in patients with IBD the mean value was 0.462 cm. Whereas previous authors said that ultrasonographic findings in cats with lymphocytic lymphoma are usually indistinguishable from patients with inflammatory bowel disease and that the wall thickness in both cases may be normal or increased, the analysis presented in this study was considered representative since most cases of AL corresponded to lymphocytic lymphoma. Surgery was performed on 35 cats in the study. The choice for exploratory laparotomy (instead of endoscopy for example) was to collect all layers of the intestinal segment, and it was successful, as all samples were representative and allowed the definitive diagnosis. Histopathology revealed 19 cases of alimentary lymphoma, 10 cases of inflammatory bowel disease, 7 cases of intestinal adenocarcinoma, 2 cases of intestinal mast cell tumor and 2 cases of intestinal hemangiosarcoma. The prevalence of AL over IBD has been previously discussed, but the occurrence of adenocarcinoma and mast cell tumor was higher in the present study. On feline physical examination, attention should be directed to abdominal palpation, since this study showed that 47.5% of the animals had intestinal wall thickening. The ultrasonographic evaluation and histopathological diagnosis is essential for the clinical management of cats with intestinal diseases.

Histological examination of rat small intestine after surgical removal of obturation small bowel obstruction and peptide stimulation of lymph flow

2018 ◽  
pp. 157-162
Author(s):  
А.А. Коваленко ◽  
Г.П. Титова ◽  
В.К. Хугаева
Keyword(s):  
Small Intestine ◽  
Surgical Treatment ◽  
Survival Rate ◽  
Small Bowel ◽  
Goblet Cells ◽  
Intestinal Wall ◽  
Structure And Function ◽  
Lymph Flow ◽  
Intestinal Lumen ◽  
And Function

Оперативное лечение различных заболеваний кишечника сопровождается осложнениями в виде нарушений микроциркуляции в области анастомоза кишки. Ранее нами показана способность лимфостимуляторов пептидной природы восстанавливать нарушенную микроциркуляцию, что послужило основой для настоящего исследования. Цель работы - оценка влияния стимуляции лимфотока в стенке кишки на процессы восстановления микроциркуляции, структуры и функции тонкой кишки в области оперативного вмешательства. Методика. В экспериментах на наркотизированных крысах (хлоралгидрат в дозе 0,6 г/кг в 0,9% растворе NaCl) моделировали различные поражения тонкой кишки (наложение лигатуры, перевязка 1-3 брыжеечных артерий, перекрут петли кишки вокруг оси брыжейки, сочетание нескольких видов повреждений). Резекция поврежденного участка через 1 сут. с последующим созданием тонкокишечного анастомоза завершалась орошением операционного поля раствором пептида-стимулятора лимфотока (40 мкг/кг массы животного в 1 мл 0,9% раствора NaCl). На 7-е сут. после операции проводили гистологическое исследование фрагмента кишки в области анастомоза. Результаты. На 7-е сут. после резекции у выживших животных (летальность вследствие кишечной непроходимости составляла 30%) имеют место морфологические признаки острых сосудистых нарушений стенки кишки, изменений кровеносных и лимфатических микрососудов, интерстициальный отек всех слоев стенки кишки, дилатация просвета кишки, повреждение всасывающего эпителия ворсин с истончением щеточной каемки клеток, морфологические признаки гиперфункции бокаловидных клеток. Использование лимфостимулятора пептидной природы после операции увеличивало выживаемость животных на 24%. У части животных отмечалось уменьшение расширения просвета кишки, у других практически полная его нормализация. Восстанавливалась форма кишечных ворсин и распределение бокаловидных клеток. Отсутствовали признаки внутриклеточного и межмышечного отека. Отмечено умеренное полнокровие венул. Заключение. Использование лимфостимулятора при хирургическом лечении кишечной непроходимости увеличивает выживаемость животных на 24% по сравнению с контролем, способствует более раннему восстановлению структуры и функции тонкой кишки. Полученные результаты свидетельствуют о перспективности использования стимуляции лимфотока при операциях на кишечнике. Surgical treatment of bowel diseases is associated with complications that cause microcirculatory disturbances in the anastomosis area and may lead to a fatal outcome. This study was based on our previous finding that peptide-type lymphatic stimulators are able to restore impaired microcirculation. The aim of this work was stimulating the lymph flow in the intestinal wall to facilitate recovery of microcirculation, structure and function of the small intestine in the area of surgical intervention. Methods. In experiments on anesthetized rats (0.6 g/kg chloral hydrate in 0.9% NaCl), various small bowel lesions were modeled (bowel ligation, ligation of 1-3 mesenteric arteries, gut torsion, combination of several lesion types). In 24 h, the damaged area was resected, and a small intestine anastomosis was creased. The surgery was completed with irrigation of the operative field with a solution of lymph flow stimulating peptide (40 мg/kg body weight in 1 ml of 0.9% NaCl). A gut fragment from the anastomosis area was examined histologically on day 7 after the surgery. Results. On the 7th day after removing the intestinal obstruction, the surviving animals (lethality 30%) had morphological signs of acute vascular disorders in the intestinal wall; changes in blood and lymphatic microvessels; interstitial edema of all intestinal wall layers; dilatation of the intestinal lumen; damage to the absorptive epithelium of villi with thinning of the brush border, and hyperfunction of mucous (goblet) cells. The use of the peptide after surgery increased the survival rate of animals by 24% and provided a smaller dilatation of the intestinal lumen in some animals. In other animals, the lumen recovered. The shape of intestinal villi and distribution of goblet cells were restored. Signs of intracellular and intermuscular edema were absent. Moderate venular congestion was noticed. Conclusion. Using the lymphatic stimulator in surgical treatment of intestinal obstruction increases the survival rate of animals by 24% compared to the control, facilitates earlier restoration of the small intestine structure and function. The obtained results indicated the effectiveness of lymphatic stimulation in intestinal surgery.

Enzymes as a Reservoir of Host Defence Peptides

2020 ◽  
Vol 20 (14) ◽  
pp. 1310-1323
Author(s):  
Andrea Bosso ◽  
Antimo Di Maro ◽  
Valeria Cafaro ◽  
Alberto Di Donato ◽  
Eugenio Notomista ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Biological Activity ◽  
Internal Structure ◽  
Catalytic Properties ◽  
Cellular Responses ◽  
Host Defence ◽  
Present Review ◽  
Active Peptides ◽  
Wide Range

Host defence peptides (HDPs) are powerful modulators of cellular responses to various types of insults caused by pathogen agents. To date, a wide range of HDPs, from species of different kingdoms including bacteria, plant and animal with extreme diversity in structure and biological activity, have been described. Apart from a limited number of peptides ribosomally synthesized, a large number of promising and multifunctional HDPs have been identified within protein precursors, with properties not necessarily related to innate immunity, consolidating the fascinating hypothesis that proteins have a second or even multiple biological mission in the form of one or more bio-active peptides. Among these precursors, enzymes constitute certainly an interesting group, because most of them are mainly globular and characterized by a fine specific internal structure closely related to their catalytic properties and also because they are yet little considered as potential HDP releasing proteins. In this regard, the main aim of the present review is to describe a panel of HDPs, identified in all canonical classes of enzymes, and to provide a detailed description on hydrolases and their corresponding HDPs, as there seems to exist a striking link between these structurally sophisticated catalysts and their high content in cationic and amphipathic cryptic peptides.

scholarly journals Optimize Design of Run-Flat Tires by Simulation and Experimental Research

Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 474
Author(s):  
Huaqiao Liu ◽  
Yiren Pan ◽  
Huiguang Bian ◽  
Chuansheng Wang
Keyword(s):  
Stress Distribution ◽  
Energy Loss ◽  
Successful Implementation ◽  
Performance Tests ◽  
Key Factors ◽  
Heat Accumulation ◽  
Factors Affecting ◽  
Structural Rigidity ◽  
Key Factor ◽  
Durability Testing

In this study, the two key factors affecting the thermal performance of the insert rubber and stress distribution on the tire sidewall were analyzed extensively through various performance tests and simulations to promote the development of run-flat tires. Four compounds and two structures of insert rubber were designed to investigate the effects of heat accumulation and stress distribution on durability testing at zero pressure. It was concluded that the rigidity and tensile strength of the compound were negatively correlated with temperature. The deformation was a key factor that affects energy loss, which could not be judged solely by the loss factor. The stress distribution, however, should be considered in order to avoid early damage of the tire caused by stress concentration. On the whole, the careful balance of mechanical strength, energy loss, and structural rigidity was the key to the optimal development of run-flat tires. More importantly, the successful implementation of the simulations in the study provided important and useful guidance for run-flat tire development.

Therapy discontinuation in a primary care psychological service: why patients drop out

2020 ◽  
Vol 13 ◽  
Author(s):  
Aisan Ghaemian ◽  
Mahdi Ghomi ◽  
Miles Wrightman ◽  
Colm Ellis-Nee
Keyword(s):  
Drop Out ◽  
Treatment Withdrawal ◽  
List Type ◽  
Structured Interviews ◽  
Group Settings ◽  
Psychological Therapies ◽  
Psychological Service ◽  
Wide Range ◽  
Key Factor ◽  
Therapy Services

Abstract The present study aimed to explore patients’ experience with an Improving Access to Psychological Therapies (IAPT) service, and to investigate the reasons for discontinuing their treatment. A qualitative approach was adopted using thematic analysis of semi-structured interviews carried out with 818 patients attending for treatment in Talking Change from November 2015 to January 2019, retrospectively. The five main themes that emerged from the study were: ‘Felt better’, ‘Issues with group settings’, ‘Therapeutic alliance breakdown’, ‘Miscommunication’ and ‘Impracticalities’. The qualitative study uncovered a wide range of reasons for people who had dropped out from their treatment. The findings mainly emphasised general dissatisfaction and inconvenient appointments. However, improvement in symptoms of depression and anxiety was also identified as a key factor among patients who discontinued their treatment. This recovery is known as ‘progress withdrawal’ in which patients withdraw from treatment early due to good therapeutic progress. We present clinical and procedural implications arising from these themes. Key learning aims (1) To explore what can cause discontinuation of therapy. (2) To obtain the experience of people who have received treatment and dropped out from Talking Change Psychological Therapy services. (3) To explore whether people recovered as part of the treatment withdrawal and what may have helped towards that recovery.

From detente to containment: the emergence of Iran's new Saudi strategy

2021 ◽  
Author(s):  
Hassan Ahmadian ◽  
Payam Mohseni
Keyword(s):  
Decision Making ◽  
Saudi Arabia ◽  
Middle East ◽  
Strategic Decision ◽  
Key Factors ◽  
Peace And Conflict ◽  
Key Factor ◽  
Decision Making Factors ◽  
Containment Strategy ◽  
The Persian Gulf

Abstract Iran's strategy with respect to Saudi Arabia is a key factor in the complex balance of power of the Middle East as the Iranian–Saudi rivalry impacts the dynamics of peace and conflict across the region from Yemen to Syria, Lebanon, Iraq and Bahrain. What is Iranian strategic thinking on Saudi Arabia? And what have been the key factors driving the evolution of Iranian strategy towards the Kingdom? In what marks a substantive shift from its previous detente policy, we argue that Tehran has developed a new containment strategy in response to the perceived threat posed by an increasingly prox-active Saudi Arabia in the post-Arab Spring period. Incorporating rich fieldwork and interviews in the Middle East, this article delineates the theoretical contours of Iranian containment and contextualizes it within the framework of the Persian Gulf security architecture, demonstrating how rational geopolitical decision-making factors based on a containment strategy, rather than the primacy of sectarianism or domestic political orientations, shape Iran's Saudi strategy. Accordingly, the article traces Iranian strategic decision-making towards the Kingdom since the Islamic Revolution of 1979 and examines three cases of Iran's current use of containment against Saudi Arabia in Syria, Yemen and Qatar.

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