Natural defense by saliva and mucosa against oral infection by Leptospira

Leptospirosis caused by drinking water has not been as frequently reported as percutaneous infection. Resistance to oral infection by pathogenic Leptospira was examined in an experimental hamster infection model. The results suggested some natural defenses against oral infection by Leptospira. First, we found that characteristic linear agglutination of Leptospira rapidly occurs when mixed with human saliva. That human saliva attenuated the infectivity of the treated leptospires by its agglutination activity suggested saliva to be the first line of defense against oral infection by leptospires. Second, only 101 Leptospira organisms caused death after submucosal injection into oral mucosa in hamsters, but oral infection with drinking water containing 105 organisms/mL did not cause death. This result showed that the mucosa plays the role of a physical barrier. Third, hamsters intragastrically infected by leptospires, with doses lethal to hamsters in oral infection, showed no signs of illness, which suggested that gastric acid plays an important role in preventing oral infection. Based on these results, saliva, mucosa, and gastric acid make up a natural defense, which confers high resistance to hosts against oral infection by leptospires.

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The Role of ST2 Receptor in the Regulation of Brucella abortus Oral Infection

Pathogens ◽

10.3390/pathogens9050328 ◽

2020 ◽

Vol 9 (5) ◽

pp. 328

Author(s):

Raiany Santos ◽

Priscila C. Campos ◽

Marcella Rungue ◽

Victor Rocha ◽

David Santos ◽

...

Keyword(s):

Intestinal Permeability ◽

Knockout Mice ◽

Brucella Abortus ◽

Immune Modulation ◽

Oral Infection ◽

Infection Model ◽

Bacterial Colony ◽

Epithelium Regeneration ◽

St2 Receptor

The ST2 receptor plays an important role in the gut such as permeability regulation, epithelium regeneration, and promoting intestinal immune modulation. Here, we studied the role of ST2 receptor in a murine model of oral infection with Brucella abortus, its influence on gut homeostasis and control of bacterial replication. Balb/c (wild-type, WT) and ST2 deficient mice (ST2−/−) were infected by oral gavage and the results were obtained at 3 and 14 days post infection (dpi). Our results suggest that ST2−/− are more resistant to B. abortus infection, as a lower bacterial colony-forming unit (CFU) was detected in the livers and spleens of knockout mice, when compared to WT. Additionally, we observed an increase in intestinal permeability in WT-infected mice, compared to ST2−/− animals. Breakage of the intestinal epithelial barrier and bacterial dissemination might be associated with the presence of the ST2 receptor; since, in the knockout mice no change in intestinal permeability was observed after infection. Together with enhanced resistance to infection, ST2−/− produced greater levels of IFN-γ and TNF-α in the small intestine, compared to WT mice. Nevertheless, in the systemic model of infection ST2 plays no role in controlling Brucella replication in vivo. Our results suggest that the ST2 receptor is involved in the invasion process of B. abortus by the mucosa in the oral infection model.

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Social Representations and Commitment

European Psychologist ◽

10.1027/1016-9040/a000317 ◽

2018 ◽

Vol 23 (3) ◽

pp. 233-249 ◽

Cited By ~ 4

Author(s):

Eric Bonetto ◽

Fabien Girandola ◽

Grégory Lo Monaco

Keyword(s):

Social Representations ◽

Social Representation ◽

Second Line ◽

Review Of The Literature ◽

First Line ◽

Research Perspectives ◽

The Social ◽

Bibliographic Search ◽

English Articles

Abstract. This contribution consists of a critical review of the literature about the articulation of two traditionally separated theoretical fields: social representations and commitment. Besides consulting various works and communications, a bibliographic search was carried out (between February and December, 2016) on various databases using the keywords “commitment” and “social representation,” in the singular and in the plural, in French and in English. Articles published in English or in French, that explicitly made reference to both terms, were included. The relations between commitment and social representations are approached according to two approaches or complementary lines. The first line follows the role of commitment in the representational dynamics: how can commitment transform the representations? This articulation gathers most of the work on the topic. The second line envisages the social representations as determinants of commitment procedures: how can these representations influence the effects of commitment procedures? This literature review will identify unexploited tracks, as well as research perspectives for both areas of research.

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A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

Era s journal of medical research ◽

10.24041/ejmr2020.34 ◽

2020 ◽

Vol 7 (2) ◽

pp. 205-211

Author(s):

Kaynat Fatima ◽

Syed Tasleem Raza ◽

Ale Eba ◽

Sanchita Srivastava ◽

Farzana Mahdi

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Protein Kinases ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Line Treatment ◽

First Line ◽

First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

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The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs

Current Medicinal Chemistry ◽

10.2174/0929867324666171012120937 ◽

2018 ◽

Vol 25 (23) ◽

pp. 2627-2636 ◽

Cited By ~ 2

Author(s):

Vincenzo Calderone ◽

Alma Martelli ◽

Eugenia Piragine ◽

Valentina Citi ◽

Lara Testai ◽

...

Keyword(s):

Physiological Role ◽

Clinical Use ◽

Diuretic Activity ◽

First Line ◽

Potassium Homeostasis ◽

Diuretic Drugs ◽

Pharmacological Target ◽

Diuretic Agents ◽

Effective Drugs

In the last four decades, the several classes of diuretics, currently available for clinical use, have been the first line option for the therapy of widespread cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable risk/benefit balance. However, they are not devoid of side effects. In particular, all the classes of diuretics cause alteration of potassium homeostasis. <p> In recent years, understanding of the physiological role of the renal outer medullary potassium (ROMK) channels, has shown an intriguing pharmacological target for developing an innovative class of diuretic agents: the ROMK inhibitors. This novel class is expected to promote diuretic activity comparable to (or even higher than) that provided by the most effective drugs used in clinics (such as furosemide), with limited effects on potassium homeostasis. <p> In this review, the physio-pharmacological roles of ROMK channels in the renal function are reported, along with the most representative molecules which have been currently developed as ROMK inhibitors.

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ROLE OF SCIENCE IN POLICY, SYSTEMS STRENGTHENING AND SUSTAINABLE SERVICE DELIVERY OF ARSENIC SAFE DRINKING WATER

10.1130/abs/2019am-335927 ◽

2019 ◽

Author(s):

Prosun Bhattacharya ◽

◽

Md. Tahmidul Islam ◽

Dara Johnston ◽

Nargis Akter ◽

...

Keyword(s):

Drinking Water ◽

Service Delivery ◽

Safe Drinking Water ◽

Policy Systems

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Deciphering the role of ttrA and pduA genes for Salmonella enterica serovars in a chicken infection model

Avian Pathology ◽

10.1080/03079457.2021.1909703 ◽

2021 ◽

pp. 1-41

Author(s):

MMS Saraiva ◽

LB Rodrigues Alves ◽

DFM Monte ◽

TS Ferreira ◽

VP Benevides ◽

...

Keyword(s):

Salmonella Enterica ◽

Infection Model

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Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide

Perfusion ◽

10.1177/0267659120986532 ◽

2021 ◽

pp. 026765912098653

Author(s):

Hafiz Naderi ◽

Shaun Robinson ◽

Martin J Swaans ◽

Nina Bual ◽

Wing-See Cheung ◽

...

Keyword(s):

Viral Load ◽

Potential Role ◽

Assessment Tool ◽

High Viral Load ◽

First Line ◽

Scanning Time ◽

Contagious Disease ◽

Core Dataset ◽

Clinical Questions

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

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Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications

Molecules ◽

10.3390/molecules26113418 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3418

Author(s):

Grzegorz Grześk ◽

Alicja Nowaczyk

Keyword(s):

Guanylate Cyclase ◽

Natriuretic Peptides ◽

Soluble Guanylate Cyclase ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Pharmacological Intervention ◽

First Line ◽

Phosphodiesterase Type ◽

Activity Mechanism

For years, guanylate cyclase seemed to be homogenic and tissue nonspecific enzyme; however, in the last few years, in light of preclinical and clinical trials, it became an interesting target for pharmacological intervention. There are several possible options leading to an increase in cyclic guanosine monophosphate concentrations. The first one is related to the uses of analogues of natriuretic peptides. The second is related to increasing levels of natriuretic peptides by the inhibition of degradation. The third leads to an increase in cyclic guanosine monophosphate concentration by the inhibition of its degradation by the inhibition of phosphodiesterase type 5. The last option involves increasing the concentration of cyclic guanosine monophosphate by the additional direct activation of soluble guanylate cyclase. Treatment based on the modulation of guanylate cyclase function is one of the most promising technologies in pharmacology. Pharmacological intervention is stable, effective and safe. Especially interesting is the role of stimulators and activators of soluble guanylate cyclase, which are able to increase the enzymatic activity to generate cyclic guanosine monophosphate independently of nitric oxide. Moreover, most of these agents are effective in chronic treatment in heart failure patients and pulmonary hypertension, and have potential to be a first line option.

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Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis

Cell Death and Disease ◽

10.1038/s41419-020-03346-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Min Lu ◽

Xinglei Qin ◽

Yajun Zhou ◽

Gang Li ◽

Zhaoyang Liu ◽

...

Keyword(s):

Acquired Resistance ◽

Transcriptional Regulators ◽

First Line ◽

Protein Coding ◽

Gemcitabine Resistance ◽

Non Coding Rna ◽

Sphere Formation ◽

Long Non Coding Rna ◽

Line Chemotherapy

AbstractGemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.

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