Structure-activity relation among macrolide antibiotics in initiation of interdigestive migrating contractions in the canine gastrointestinal tract

1985 ◽  
Vol 248 (3) ◽  
pp. G320-G325 ◽  
Author(s):  
Z. Itoh ◽  
T. Suzuki ◽  
M. Nakaya ◽  
M. Inoue ◽  
H. Arai ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Chemical Structure ◽  
Conscious Dogs ◽  
Macrolide Antibiotics ◽  
Glycosidic Linkage ◽  
Structure Activity ◽  
Endogenous Release ◽  
Interdigestive Migrating Contractions

The relation between the chemical structure of commercially available macrolide antibiotics and their activity in inducing interdigestive migrating contractions (IMC) was studied in conscious dogs. It was found that the 14-membered macrolides erythromycin and oleandomycin are active in inducing IMC in the stomach in association with the endogenous release of motilin. These erythromycin- and oleandomycin-induced contractions in the stomach migrated through the small intestine in a caudad direction. Conversely, 16-membered macrolide antibiotics such as leucomycin, acetylspiramycin, and tylosin do not induce any contractions in the stomach or stimulate endogenous release of motilin. These findings suggest that the IMC-inducing activity in macrolides seems to be closely related to their chemical configuration, i.e., the structure of 14-membered macrolides with dimethylaminosugar (desosamine) bound at C-5 and neutralsugar at C-3 in glycosidic linkage in parallel is likely to be necessary for IMC-inducing activity. The mechanisms by which erythromycin and oleandomycin stimulate endogenous motilin release are not known.

Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog

1984 ◽  
Vol 247 (6) ◽  
pp. G688-G694 ◽  
Author(s):  
Z. Itoh ◽  
M. Nakaya ◽  
T. Suzuki ◽  
H. Arai ◽  
K. Wakabayashi
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Intravenous Infusion ◽  
Contractile Activity ◽  
Contractile Force ◽  
Naturally Occurring ◽  
Gastrointestinal Motor ◽  
Plasma Motilin ◽  
Interdigestive Migrating Contractions ◽  
Gastrointestinal Contractile Activity

The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs. It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50–100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum. The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration. The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions. Like motilin, EM stimulated motor activity only during the interdigestive state. We conclude that EM induces IMC associated with the release of endogenous motilin in the dog.

CHANGES IN SMALL INTESTINE MICROFLORA IN PATIENTS WITH ACUTE INTESTINAL OBSTRUCTION

2020 ◽  
pp. 16-18
Author(s):  
V. M. Lykhman ◽  
O. M. Shevchenko ◽  
Ye. O. Bilodid ◽  
Igor Vladimirovich Volchenko ◽  
I. A. Kulyk ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Species Composition ◽  
Intestinal Obstruction ◽  
Bacterial Flora ◽  
Anaerobic Bacteria ◽  
Acute Intestinal Obstruction ◽  
Gram Positive ◽  
Mechanical Intestinal Obstruction ◽  
Facultative Anaerobic Bacteria

Among urgent surgical diseases of abdominal cavity, an acute intestinal obstruction is the most difficult to be diagnosed and treated. Leading factor, determining the development of pathophysiological processes is considered to be the progressive manifestations of enteric insufficiency syndrome, resulting in intestinal barrier impairment, negative changes in ecology of intestinal flora, increased endotoxins. To identify the small intestine microflora in acute intestinal obstruction and determine the role of dysbiotic disorders in clinical manifestations of main pathological process, a study was conducted in 60 patients with mechanical intestinal obstruction. The small intestine has a relatively rare microflora, consisting mainly of gram−positive facultative aerobic microorganisms, streptococci, lactobacilli. The distal ileum in nearly 30−55 % of healthy people contains scanty microflora, and yet the flora of this area differs from the microbial population of the higher gastrointestinal tract due to higher concentration of gram−negative bacteria. Optional−anaerobic coliform bacilli, anaerobic bifidobacteria and fusobacteria, bacteroids, the number of which starts exceeding the one of gram−positive species, are presented in significant quantities. Distal to the ileocecal valve there are significant changes in the microflora quantitative and species composition. Obligatory anaerobic bacteria become the predominant part of microflora, exceeding the number of aerobic and facultative anaerobic bacteria. The bacterial flora in different parts of gastrointestinal tract has its own specifics and is quite constant, as a result of the interaction of many factors, regulating the bacterial population in small intestine. The most important among them are: acidity of gastric juice, normal peristaltic activity of the intestine, bacterial interactions and immune mechanisms. Disorders of the intestine motor and evacuation function with its obstruction lead to slow passage of the chyme and contamination of the upper gastrointestinal tract with new types of microbes. There is a syndrome of small intestine excessive colonization, which means an increased concentration of bacterial populations in it, similar in species composition to the colon microflora. Pathological intra−intestinal contents become a source of endogenous infection and re−infection of the patient, leads to internal digestive disorders, which is manifested by syndrome of malabsorption of proteins, carbohydrates and vitamins. Key words: acute intestinal obstruction, small intestinal microflora, conditionally pathogenic microorganisms, intestinal biocenosis.

An Update on JAK Inhibitors

2019 ◽  
Vol 26 (10) ◽  
pp. 1806-1832 ◽  
Author(s):  
Francesca Musumeci ◽  
Chiara Greco ◽  
Ilaria Giacchello ◽  
Anna Lucia Fallacara ◽  
Munjed M. Ibrahim ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinases ◽  
Chemical Structure ◽  
Receptor Tyrosine Kinases ◽  
Myeloproliferative Neoplasms ◽  
Pharmaceutical Companies ◽  
Jak Inhibitors ◽  
Pyrimidine Derivatives ◽  
Janus Kinases ◽  
Structure Activity

Janus kinases (JAKs) are a family of non-receptor tyrosine kinases, composed by four members, JAK1, JAK2, JAK3 and TYK2. JAKs are involved in different inflammatory and autoimmune diseases, as well as in malignancies, through the activation of the JAK/STAT signalling pathway. Furthermore, the V617F mutation in JAK2 was identified in patients affected by myeloproliferative neoplasms. This knowledge prompted researchers from academia and pharmaceutical companies to investigate this field in order to discover small molecule JAK inhibitors. These efforts recently afforded to the market approval of four JAK inhibitors. Despite the fact that all these drugs are pyrrolo[2,3-d]pyrimidine derivatives, many compounds endowed with different heterocyclic scaffolds have been reported in the literature as selective or multi-JAK inhibitors, and a number of them is currently being evaluated in clinical trials. In this review we will report many representative compounds that have been published in articles or patents in the last five years (period 2013-2017). The inhibitors will be classified on the basis of their chemical structure, focusing, when possible, on their structure activity relationships, selectivity and biological activity. For every class of derivatives, compounds disclosed before 2013 that have entered clinical trials will also be briefly reported, to underline the importance of a particular chemical scaffold in the search for new inhibitors.

Cytotoxic Constituents from the Bark of Erythrina poeppigiana Against the MCF-7 Breast Cancer Cell Lines

2020 ◽  
Vol 10 (3) ◽  
pp. 257-261
Author(s):  
Tati Herlina ◽  
Merlin ◽  
Mohd. Azlan ◽  
Unang Supratman
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Chemical Structure ◽  
Breast Cancer Cell Lines ◽  
Erythrina Poeppigiana ◽  
Structure Activity ◽  
Cancer Line ◽  
Cytotoxic Compounds ◽  
Ic50 Values ◽  
Mcf 7

Background: Erythrina poeppigiana (Leguminosae) is a high-growing plant with an orange flower that is widely distributed in tropical and subtropical countries. This particular plant is widely used in traditional medicine for gynecological complications and the treatment of various diseases. There exists no previous information regarding cytotoxic compounds from this plant. Objective: This research is to isolate cytotoxic compounds from E. poeppigiana. Methods: The isolation step was carried out using a combination of chromatographic techniques to obtain isolated three compounds (1, 2, and 3). Results: The chemical structure of isolated compounds was elucidated by spectroscopic methods and identified as β-erythroidine (1), 8-oxo-β-erythroidine (2), and 8-oxo-α-erythroidine (3). Compounds (1-3) showed cytotoxic activity against MCF-7 breast cancer line with IC50 values of 36.8, 60.8 and 875.4 μM, respectively. Conclusion: Three compounds have been successfully isolated from Erythrina poeppigiana (Leguminosae), showing cytotoxic properties against MCF-7 breast cancer line. Structure-activity relationship studies showed that the presence of enone moiety on compound 1 can reduce its cytotoxic activity towards MCF-7 breast cancer line.

scholarly journals A long-term survivor of clear cell sarcoma-like tumor of the gastrointestinal tract with liver metastasis: a case report

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Takuhisa Okada ◽  
Yasumitsu Hirano ◽  
Shintaro Ishikawa ◽  
Hiroka Kondo ◽  
Toshimasa Ishii ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lymph Node ◽  
Gastrointestinal Tract ◽  
Liver Metastasis ◽  
Surgical Resection ◽  
Clear Cell ◽  
Clear Cell Sarcoma ◽  
Cell Sarcoma

Abstract Background Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLTGT) is extremely rare. It is a mesenchymal neoplasm that usually forms in the small intestine of adolescents and young adults, is prone to local recurrence and metastasis, and has a high mortality rate. We report a patient with CCSLTGT with lymph node- and liver metastases, who continues to survive 6 years after initial surgical resection. Case presentation A 38-year-old woman presented with lightheadedness. Laboratory analysis revealed anemia (hemoglobin, 6.7 g/dL), and enhanced computed tomography (CT) demonstrated a mass in the small intestine, about 6 cm in diameter, with swelling of 2 regional lymph nodes. Double-balloon small intestine endoscopic examination revealed a tumor accompanied by an ulcer; the biopsy findings suggested a primary cancer of the small intestine. She was admitted, and we then performed a laparotomy for partial resection of the small intestine with lymph node dissection. Pathologic examination revealed CCSLTGT with regional lymph node metastases. About 3 years later, follow-up CT revealed a single liver metastasis. Consequently, she underwent a laparoscopic partial liver resection. Histopathologic examination confirmed that the liver metastasis was consistent with CCSLTGT. It has now been 3 years without a recurrence. Conclusion Repeated radical surgical resection with close follow-up may be the only way to achieve long-term survival in patients with CCLSTGT.

scholarly journals Metastatic Melanoma Presenting as Intussusception in an 80-Year-Old Man: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Sarah Alghamdi ◽  
Yumna Omarzai
Keyword(s):  
Differential Diagnosis ◽  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Metastatic Melanoma ◽  
Clinical Presentation ◽  
Gastrointestinal Symptoms ◽  
Common Site ◽  
Neoplastic Process ◽  
History Of ◽  
Uncommon Neoplasm

Malignant melanoma of the gastrointestinal tract is an uncommon neoplasm that could be primary or metastatic. Small intestine represents the most common site for the metastatic melanoma; however, it could be found anywhere in the gastrointestinal tract. Intussusception is a rare cause of intestinal obstruction in adults compared to children. In 90% of the cases, the underlying cause can be found, and in 65% of the cases, intussusception is caused by the neoplastic process. The majority of the neoplasms are benign, and about 15% are malignant. Metastatic melanoma is one of the most common metastatic malignancies to the gastrointestinal tract; however, the premortem diagnosis is rarely made. Here, we report an uncommon clinical presentation of metastatic melanoma causing intussusception in an 80-year-old man. This diagnosis should be considered in a differential diagnosis in any patient who presents with gastrointestinal symptoms and a history of melanoma.

WZsGreen/+: a new green fluorescent protein knock-in mouse model for the study of KIT-expressing cells in gut and cerebellum

2005 ◽  
Vol 22 (3) ◽  
pp. 412-421 ◽  
Author(s):  
Mira Wouters ◽  
Karine Smans ◽  
Jean-Marie Vanderwinden
Keyword(s):  
Small Intestine ◽  
Green Fluorescent Protein ◽  
Gastrointestinal Tract ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Molecular Layer ◽  
Transgenic Animals ◽  
The Novel ◽  
Suitable Alternative ◽  
Green Fluorescent

In the small intestine, interstitial cells of Cajal (ICC) surrounding the myenteric plexus generate the pacemaking slow waves that are essential for an efficient intestinal transit. The underlying molecular mechanisms of the slow wave are poorly known. KIT is currently the sole practical marker for ICC. Attempts to purify living ICC have so far largely failed, due to the loss of the KIT epitope during enzymatic dissociation. Aiming to identify and isolate living ICC, we designed a knock-in strategy to express a fluorescent tag in KIT-expressing cells by inserting the sequence of the novel green fluorescent protein ZsGreen into the first exon of the c-Kit gene, creating a null allele called WZsGreen. In the gastrointestinal tract of heterozygous WZsGreen/+ mice, tiny ZsGreen fluorescent dots were observed in all KIT-expressing ICC populations, with exception of ICC at the deep muscular plexus in small intestine. During development of the gastrointestinal tract, ZsGreen expression followed KIT expression in a spatiotemporal way. Stellate and basket KIT-expressing cells in the molecular layer of the cerebellum also exhibited ZsGreen dots, whereas no ZsGreen was detected in skin, testis, and bone marrow. ZsGreen dot-containing intestinal cells could be isolated from jejunum and maintained alive in culture for at least 3 days. ZsGreen is a suitable alternative to EGFP in transgenic animals. The novel WZsGreen/+ model reported here appears to be a promising tool for live studies of KIT-expressing cells in the gastrointestinal tract and cerebellum and for the further analysis of pacemaker mechanisms.

Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract in the small intestine: A case report

2017 ◽  
Vol 45 (12) ◽  
pp. 1137-1141 ◽  
Author(s):  
Takashi Kato ◽  
Shin Ichihara ◽  
Hiroko Gotoda ◽  
Shunji Muraoka ◽  
Terufumi Kubo ◽  
...  
Keyword(s):  
Small Intestine ◽  
Case Report ◽  
Gastrointestinal Tract ◽  
Clear Cell ◽  
Clear Cell Sarcoma ◽  
Imprint Cytology ◽  
Cell Sarcoma
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