scholarly journals Particularities of Experimental Models Used to Induce Gastric Ulcer

2019 ◽  
Vol 25 (4) ◽  
pp. 179-184
Author(s):  
Simona Fulga ◽  
Ana-Maria Pelin ◽  
Cristina Mihaela Ghiciuc ◽  
Elena Cătălina Lupușoru
Keyword(s):  
Gastric Ulcer ◽  
Hydrochloric Acid ◽  
Experimental Studies ◽  
Experimental Models ◽  
New Drugs ◽  
Laboratory Animals ◽  
Gastric Ulcers ◽  
Current Therapy ◽  
Surgical Methods

Abstract Introduction: Gastric ulcer is one of the most common gastrointestinal diseases, therefore the constant interest for new treatments is due to adverse effects induced by current therapy. The restricted number of in vivo experimental models is a challenge for researchers. Objectives: Identifying the particularities of different types of experimentally induced gastric ulcer in laboratory animals to facilitate their choise for the study of new antiulcer drugs. Material and method: A search in PubMed and Scopus using keywords ( “experimentally” AND “gastric ulcer” AND “rats/mice”) to include experimental studies with the description of local-induced changes. Review articles and in vitro studies were excluded. Results and discussions: Experimental researches on new drugs for gastric ulcer use chemical or surgical methods to induce gastric lesions in rats. Non-steroidal anti-inflammatory drugs (NSAIDs) and acetic acid models to investigate antisecretory and cytoprotective effects; ethanol models evaluate cytoprotective and/or antioxidant effects; pylorus ligature models to evaluate the effects on the secretion of aggressive gastric factors (hydrochloric acid or pepsin). NSAIDs (indomethacin, acetylsalicylic acid or ibuprofen) inhibit cyclooxygenase activity, resulting from reduced mucus and bicarbonate secretion, decreased mucosal blood flow, alteration of microvascular structures, causing epithelial damage Ethanol enhances the proteolytic and hydrolytic action of hydrochloric acid and pepsin; in addition, stimulates the acid secretion and disruptes vascular endothelium. Pylorus ligature determines the accumulation of gastric acid resulting in gastric ulcers due to the autodigestion of the mucosa. Conclusion: The knowledge of the mechanisms to induce experimental gastric ulcers is essential for choosing the model to evaluate new antiulcer agents.

scholarly journals In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 160
Author(s):  
Oliwia Koszła ◽  
Katarzyna M. Targowska-Duda ◽  
Ewa Kędzierska ◽  
Agnieszka A. Kaczor
Keyword(s):  
Experimental Studies ◽  
In Vitro Models ◽  
Experimental Models ◽  
Critical Discussion ◽  
New Drugs ◽  
Complex Nature ◽  
Cognitive Symptoms ◽  
In Vivo Models

Schizophrenia (SZ) is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, and is not satisfactorily treated by current antipsychotics. Progress in understanding the basic pathomechanism of the disease has been hampered by the lack of appropriate models. In order to develop modern drugs against SZ, efficient methods to study them in in vitro and in vivo models of this disease are required. In this review a short presentation of current hypotheses and concepts of SZ is followed by a description of current progress in the field of SZ experimental models. A critical discussion of advantages and limitations of in vitro models and pharmacological, genetic, and neurodevelopmental in vivo models for positive, negative, and cognitive symptoms of the disease is provided. In particular, this review concerns the important issue of how cellular and animal systems can help to meet the challenges of modeling the disease, which fully manifests only in humans, as experimental studies of SZ in humans are limited. Next, it is emphasized that novel clinical candidates should be evaluated in animal models for treatment-resistant SZ. In conclusion, the plurality of available in vitro and in vivo models is a consequence of the complex nature of SZ, and there are extensive possibilities for their integration. Future development of more efficient antipsychotics reflecting the pleiotropy of symptoms in SZ requires the incorporation of various models into one uniting model of the multifactorial disorder and use of this model for the evaluation of new drugs.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

scholarly journals MBRS-48. IDENTIFICATION OF NOVEL THERAPEUTIC APPROACHES FOR MYC-DRIVEN MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii406-iii406
Author(s):  
Kübra Taban ◽  
David Pauck ◽  
Mara Maue ◽  
Viktoria Marquardt ◽  
Hua Yu ◽  
...  
Keyword(s):  
New Drugs ◽  
Current Therapy ◽  
Cancer Drug ◽  
Mrna Levels ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Group 3 ◽  
Novel Therapeutic

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and is frequently metastatic at diagnosis. Treatment with surgery, radiation and multi-agent chemotherapy may leave survivors of these brain tumors with long-term deficits as a consequence. One of the four consensus molecular subgroups of MB is the MYC-driven group 3 MB, which is the most malignant type and has a poor prognosis under current therapy. Thus, it is important to discover more effective targeted therapeutic approaches. We conducted a high-throughput drug screening to identify novel compounds showing efficiency in group 3 MB using both clinically established inhibitors (n=196) and clinically-applicable compounds (n=464). More than 20 compounds demonstrated a significantly higher anti-tumoral effect in MYChigh (n=7) compared to MYClow (n=4) MB cell models. Among these compounds, Navitoclax and Clofarabine showed the strongest effect in inducing cell cycle arrest and apoptosis in MYChigh MB models. Furthermore, we show that Navitoclax, an orally bioavailable and blood-brain barrier passing anti-cancer drug, inhibits specifically Bcl-xL proteins. In line, we found a significant correlation between BCL-xL and MYC mRNA levels in 763 primary MB patient samples (Data source: “R2 https://hgserver1.amc.nl”). In addition, Navitoclax and Clofarabine have been tested in cells obtained from MB patient-derived-xenografts, which confirmed their specific efficacy in MYChigh versus MYClow MB. In summary, our approach has identified promising new drugs that significantly reduce cell viability in MYChigh compared to MYClow MB cell models. Our findings point to novel therapeutic vulnerabilities for MB that need to be further validated in vitro and in vivo.

scholarly journals EXPERIMENTAL STUDIES ON GASTRIC ULCER (4) SEQUENTIAL OBSERVATION AND EVALUATION OF GASTRIC ULCERS BY ENDOSCOPE IN THE RAT*

1983 ◽  
Vol 33 (1) ◽  
pp. 175-179
Author(s):  
Kazunaga FUKAWA ◽  
Osamu KAWANO ◽  
Noriyuki MISAKI ◽  
Masayuki UCHIDA ◽  
Osamu IRINO
Keyword(s):  
Gastric Ulcer ◽  
Experimental Studies ◽  
Gastric Ulcers

scholarly journals An Ethanolic Extract of Boehmeria caudata Aerial Parts Displays Anti-inflammatory and Anti-tumor Activities

2020 ◽  
Vol 7 (01) ◽  
pp. e17-e25 ◽  
Author(s):  
Paula Pereira de Paiva ◽  
Fabiana Regina Nonato ◽  
Ana Lúcia Tasca Gois Ruiz ◽  
Ilza Maria de Oliveira Sousa ◽  
Rafael Rosolen Teixeira Zafred ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Ethanolic Extract ◽  
Experimental Models ◽  
New Drugs ◽  
Antiproliferative Effects ◽  
Aerial Parts ◽  
Anti Inflammatory ◽  
Inflammatory Action ◽  
Effective Source

AbstractThe tumor microenvironment presents several therapeutic targets, with inflammation being one of them. In search of new drugs, plants have shown to be an effective source of potent anti-inflammatory and anticancer agents. This study aimed to evaluate the antitumoral and inflammatory activities of Boehmeria caudata aerial parts extract. Bioguided in vitro antiproliferative screening showed that phenanthroquinolizidine obtained from the aerial B. caudata ethanolic extract had a straight relationship with activity. Moreover, the orally administered ethanolic extract reduced Ehrlich solid tumor growth and displayed an anti-inflammatory effect in both evaluated experimental models (carrageenan-induced paw edema and croton oil-induced ear edema). These results suggest that the antitumor activity of the ethanolic extract could be explained by antiproliferative effects associated with anti-inflammatory action.

Clinical And Experimental Studies On FBG Heterogeneity And Fibrinogenolysis —Especially In DIC And UK Treatment

1981 ◽  
Author(s):  
M Yamauchi ◽  
H Takei ◽  
T Seya ◽  
Y Oguma ◽  
T Murakoshi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Fibrinolytic Activity ◽  
Experimental Studies ◽  
Experimental Models ◽  
Low Molecular Weight ◽  
Electrophoretic Patterns ◽  
Sds Page ◽  
Cirrhotic Patients ◽  
Partial Degradation

ABy means of SDS-PAGE (3.3% gel), Fbg heterogeneity originated from partial degradation of Aα chain was studied. Comparison of electrophoretic patterns of plasma and corresponding serum made it possible to identify 2 major Fbg bands designated as high-molecular-weight Fbg (HMW, MW 350,000) and low-molecular-weight Fbg (LMW, MW 310,000). LMW comprised 28×2% (mean×S.D) of total Fbg (HMW+LMW) in healty subjects. The elevation of fibrinolytic activity did not accompany the increase of percentages of LMW in various diseases, even in cirrhotic patients whose levels of α2;PI were low. In DIC patients percentages of LMW were decreased extremely (12×6%, mean×SD). Samples from animal experimental models of DIC exhibited the same pattern of Fbg heterogeneity as that of DIC patients.UK was added to the purified Fbg in vitro. On the earliest stage of the fibrinogenolysis. 2 bands appeared newly on SDS-PAGE, while the bands of HMW and LMW were decreased. One of these new bands (Band 1) corresponded with a major compornent of Fraction 1-9 of Mosesson. It was located in the slightly anodal position (MW 300,000) from LMW band. Another band (MW 270,000) migrated between Band 1 and the band of Frag X. The same pattern of Fbg heterogeneity was observed in patients recieving large dose of UK. After cessation of UK treatment these new bands disappeared, while the bands of HMW was increased extremelThese findings suggest that HMW is a freshly synthesized Fbg and that unknown mechanism without plasmin may present for the conversion HMW to LMW.

scholarly journals Potential and beneficial effects of Cinnamomum cassia on gastritis and safety: Literature review and analysis of standard extract

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Ji Hwan Lee ◽  
Do Hwi Park ◽  
Sanghyun Lee ◽  
Hye Jin Seo ◽  
Shin Jung Park ◽  
...  
Keyword(s):  
Literature Review ◽  
Evaluation System ◽  
Experimental Studies ◽  
Gastric Ulcers ◽  
Gastric Injury ◽  
Sprague Dawley ◽  
Gastric Mucus ◽  
Efficient Treatment ◽  
Cinnamomum Cassia

AbstractThe prevalence of gastritis in South Korea is rapidly increasing owing to the prevalence of Helicobacter pylori infection and fast eating habit. The usual treatment for acute gastritis following a long intake of non-steroidal anti-inflammatory drugs (NSAIDs) or alcohol is to stop the causal factors. Metronidazole and lansoprazole are recommended for the treatment of H. pylori infection gastritis. Omeprazole a proton pump inhibitor, is used to decrease gastric acid production. However, owing to the side effects and refractoriness of the drug, a safe and efficient treatment is required. Plant-derived phytochemicals have emerged as novel agents against chronic disorders. In this study, firstly, to explore the potential of pharmacological activities, including efficacy and mechanisms of Cinnamomum cassia against gastritis, a literature review was performed based on 20 studies out of a total of 749 records obtained using a search strategy. From the literature review, the therapeutic targets of C. cassia extract and cinnamaldehyde, a compound of C. cassia, were found to be related with NFκB activity, and their signaling pathway were verified by experiments. C. cassia extract plays a role in protection of gastric ulcers induced in four ways (immersion stress-induced, ethanol-induced, hydrochloric acid-induced, or NSAIDs-induced ulcer). None of the clinical studies on C. cassia extracts or compounds met our criteria. When the standardized extract of C. cassia (ECC) was orally administered repeatedly to Beagle Dog for 4 weeks, no toxicologically harmful changes were observed. Therefore, under the test condition, the no observed adverse effect level (NOAEL) of ECC was judged to be 1000 mg/kg/day for both sexes, and no toxic target organ was observed. Administration of ECC in the Sprague–Dawley rat model of acute gastric injury caused by indomethacin administration significantly increased gastric mucus volume. Administration of ECC in the acute gastric injury model caused by indomethacin administration is considered effective in improving gastric injury. However, research and efforts to develop a reliable ‘standardization of natural drugs’ by establishing the best quality evaluation system are limited. Despite the pharmacological potential of ECC, further well-designed experimental studies such as in vitro, in vivo, and clinical trials are required to validate these findings and the underlying mechanisms of ECC.

scholarly journals Experimental Model of Spinal Cord Injury (SCI) in rats: management guidelines

2013 ◽  
Vol 12 (1) ◽  
pp. 70-72 ◽  
Author(s):  
Asdrubal Falavigna ◽  
Fernanda Cechetti ◽  
Guilherme Finger ◽  
Leonardo Gilmone Ruschel ◽  
Grasiela Marcon ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Postoperative Management ◽  
Experimental Models ◽  
New Drugs ◽  
Laboratory Animals ◽  
Standard Protocol ◽  
New Techniques ◽  
Management Guidelines ◽  
Cord Injury

Surgical experiments with laboratory animals are necessary for medical research. These studies aim to clarify the mechanism of disease, investigate the action and efficacy of new drugs or biological markers, as well as develop and enhance new therapies and apply new techniques. Regarding the models of spinal cord injury (SCI), there are several different methods that address the handling of the animals, especially concerning the use of analgesics, antibiotics and pre- and postoperative management. The lack of uniformity and standardization among the studies does not allow the understanding of the model of SCI or the proper handling of the paraplegic animals, hampering the adequate interpretation and comparison of results. The goal of this study is to establish a standard protocol on the handling of animals subjected to experimental models of SCI.

scholarly journals Intestinal Anti-Inflammatory Activity of Terpenes in Experimental Models (2010–2020): A Review

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5430
Author(s):  
Maria Elaine Araruna ◽  
Catarina Serafim ◽  
Edvaldo Alves Júnior ◽  
Clelia Hiruma-Lima ◽  
Margareth Diniz ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Biological Activities ◽  
Structural Diversity ◽  
Experimental Models ◽  
New Drugs ◽  
Inflammatory Activity ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Inflammatory bowel diseases (IBDs) refer to a group of disorders characterized by inflammation in the mucosa of the gastrointestinal tract, which mainly comprises Crohn’s disease (CD) and ulcerative colitis (UC). IBDs are characterized by inflammation of the intestinal mucosa, are highly debilitating, and are without a definitive cure. Their pathogenesis has not yet been fully elucidated; however, it is assumed that genetic, immunological, and environmental factors are involved. People affected by IBDs have relapses, and therapeutic regimens are not always able to keep symptoms in remission over the long term. Natural products emerge as an alternative for the development of new drugs; bioactive compounds are promising in the treatment of several disorders, among them those that affect the gastrointestinal tract, due to their wide structural diversity and biological activities. This review compiles 12 terpenes with intestinal anti-inflammatory activity evaluated in animal models and in vitro studies. The therapeutic approach to IBDs using terpenes acts basically to prevent oxidative stress, combat dysbiosis, restore intestinal permeability, and improve the inflammation process in different signaling pathways.

Potential Therapeutic Applications of P2 Receptor Antagonists: From Bench to Clinical Trials

2019 ◽  
Vol 20 (9) ◽  
pp. 919-937 ◽  
Author(s):  
Natiele C. da Silva Ferreira ◽  
Luiz A. Alves ◽  
Rômulo J. Soares-Bezerra
Keyword(s):  
Clinical Trials ◽  
P2 Receptors ◽  
Experimental Models ◽  
New Drugs ◽  
Receptor Subtype ◽  
P2 Receptor ◽  
Receptor Antagonists ◽  
Purines And Pyrimidines

Background: Extracellular purines and pyrimidines have important physiological functions in mammals. Purines and pyrimidines act on P1 and P2 purinergic receptors, which are widely expressed in the plasma membrane in various cell types. P2 receptors act as important therapeutic targets and are associated with several disorders, such as pain, neurodegeneration, cancer, inflammation, and thrombosis. However, the use of antagonists for P2 receptors in clinical therapy, with the exception of P2Y12, is a great challenge. Currently, many research groups and pharmaceutical companies are working on the development of specific antagonist molecules for each receptor subtype that could be used as new medicines to treat their respective disorders. Objective: The present review compiles some interesting findings on the application of P2 receptor antagonists in different in vitro and in vivo experimental models as well as the progress of advanced clinical trials with these compounds. Conclusion: Despite all of the exciting results obtained on the bench, few antagonists of P2 receptors advanced to the clinical trials, and once they reach this stage, the effectiveness of the therapy is not guaranteed, as in the example of P2X7 antagonists. Despite this, P2Y12 receptor antagonists have a history of success and have been used in therapy for at least two decades to prevent thrombosis in patients at risk for myocardial infarctions. This breakthrough is the motivation for scientists to develop new drugs with antagonistic activity for the other P2 receptors; thus, in a matter of years, we will have an evolution in the field of purinergic therapy.

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