Clinical Use of OKT3: The Role of Cytokine Release and Xenosensitization

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 PURINERGIC RECEPTORS IN CELL DEATH AND CYTOKINE RELEASE IN THE IMMUNE SYSTEM

Biochemical Society Transactions ◽

10.1042/bst024560sc ◽

1996 ◽

Vol 24 (4) ◽

pp. 560S-560S

Author(s):

Davide Ferrari ◽

Martin Villalba ◽

Paola Chiozzi ◽

Monica Dal Susino ◽

Simonetta Falzoni ◽

...

Keyword(s):

Cell Death ◽

Immune System ◽

Purinergic Receptors ◽

Cytokine Release

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Additional Diagnostic Yield of Adding Serology to PCR in Diagnosing Viral Acute Respiratory Infections in Kenyan Patients 5 Years of Age and Older

Clinical and Vaccine Immunology ◽

10.1128/cvi.00325-12 ◽

2012 ◽

Vol 20 (1) ◽

pp. 113-114 ◽

Cited By ~ 17

Author(s):

Daniel R. Feikin ◽

M. Kariuki Njenga ◽

Godfrey Bigogo ◽

Barrack Aura ◽

Stella Gikunju ◽

...

Keyword(s):

Respiratory Infections ◽

Diagnostic Yield ◽

Epidemiologic Studies ◽

Acute Respiratory Infections ◽

Clinical Use ◽

Paired Sample ◽

Parainfluenza Viruses ◽

Syncytial Virus ◽

Etiologic Diagnosis

ABSTRACTThe role of serology in the setting of PCR-based diagnosis of acute respiratory infections (ARIs) is unclear. We found that acute- and convalescent-phase paired-sample serologic testing increased the diagnostic yield of naso/oropharyngeal swabs for influenza virus, respiratory syncytial virus (RSV), human metapneumovirus, adenovirus, and parainfluenza viruses beyond PCR by 0.4% to 10.7%. Although still limited for clinical use, serology, along with PCR, can maximize etiologic diagnosis in epidemiologic studies.

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Role of IL-6 inhibitor in treatment of COVID-19-related cytokine release syndrome

International Journal of Medical Sciences ◽

10.7150/ijms.53564 ◽

2021 ◽

Vol 18 (6) ◽

pp. 1356-1362

Author(s):

Peng Du ◽

Jie Geng ◽

Feng Wang ◽

Xiaobo Chen ◽

Zhiwei Huang ◽

...

Keyword(s):

Cytokine Release ◽

Cytokine Release Syndrome

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Severe eosinophilic bronchial asthma: new therapeutic options

Medical Council ◽

10.21518/2079-701x-2018-15-44-52 ◽

2018 ◽

pp. 44-52 ◽

Cited By ~ 2

Author(s):

N. M. Nenasheva

Keyword(s):

Monoclonal Antibodies ◽

Severe Asthma ◽

Bronchial Asthma ◽

Biological Agents ◽

Therapeutic Options ◽

Clinical Use ◽

Eosinophilic Asthma ◽

Interleukin 5 ◽

Severe Eosinophilic Asthma

Eosinophilic asthma is a common phenotype of severe asthma, occurring in at least half of patients. In recent years, there have been significant changes in the approaches to the treatment of severe bronchial asthma and, above all, eosinophilic asthma. The article discusses the role of eosinophils in the pathogenesis of severe asthma, the detection of the phenotype of severe eosinophilic asthma, and modern approaches to targeting severe asthma with an eosinophilic phenotype using biological agents. A special emphasis is placed on preparations of monoclonal antibodies to interleukin-5, in particular, mepolizumab, recently approved for clinical use in our country.

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Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms20092241 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2241 ◽

Cited By ~ 27

Author(s):

Debarati Banik ◽

Sara Moufarrij ◽

Alejandro Villagra

Keyword(s):

Histone Deacetylase Inhibitors ◽

Critical Role ◽

Preclinical Studies ◽

Clinical Use ◽

Combination Therapies ◽

Drug Candidates ◽

Cellular Processes ◽

Fda Approval

Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. Finally, we have included examples of ongoing trials for each of the above categories of HDACis as standalone agents or in combination with immunotherapeutic approaches.

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Polarized Cytokine Release Triggered by P2X7 Receptor from Retinal Pigmented Epithelial Cells Dependent on Calcium Influx

Cells ◽

10.3390/cells9122537 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2537

Author(s):

Xiaolei Shao ◽

Sonia Guha ◽

Wennan Lu ◽

Keith E. Campagno ◽

Jonathan M. Beckel ◽

...

Keyword(s):

P2x7 Receptor ◽

Calcium Influx ◽

Inflammatory Cells ◽

Cytokine Signaling ◽

Cytokine Release ◽

Rpe Cells ◽

Primary Mouse ◽

Retinal Neurodegeneration ◽

Apical Membranes

Cytokine release from non-inflammatory cells is a key step in innate immunity, and agonists triggering cytokine release are central in coordinating responses. P2X7 receptor (P2X7R) stimulation by extracellular ATP is best known to active the NLRP3 inflammasome and release IL-1β, but stimulation also leads to release of other cytokines. As cytokine signaling by retinal pigmented epithelial (RPE) cells is implicated in retinal neurodegeneration, the role of P2X7R in release of cytokine IL-6 from RPE cells was investigated. P2X7R stimulation triggered IL-6 release from primary mouse RPE, human iPS-RPE and human ARPE-19 cells. IL-6 release was polarized, with predominant rise across apical membranes. IL-6 release was inhibited by P2X7R antagonists A438079, A839977, and AZ10606120, but not the NRTI lamivudine (3TC), P2X1R antagonist NF279, or P2Y1R antagonist MRS2179. P2X7R-mediated IL-6 release required extracellular Ca2+ and was blocked by Ca2+ chelator BAPTA. IL-6 release and Ca2+ elevation occurred rapidly, consistent with vesicular IL-6 staining in unstimulated cells. P2X7R stimulation did not trigger IL-1β release in these unprimed cells. P2X7R-mediated IL-6 release was enhanced in RPE cells from the ABCA4−/− mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca2+-dependent IL-6 release across the apical membrane of RPE cells.

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Neurohormonal Modulation as a Therapeutic Target in Pulmonary Hypertension

Cells ◽

10.3390/cells9112521 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2521

Author(s):

Inés García-Lunar ◽

Daniel Pereda ◽

Borja Ibanez ◽

Ana García-Álvarez

Keyword(s):

Pulmonary Hypertension ◽

State Of The Art ◽

Beta Blockers ◽

Cardiovascular Disorders ◽

Clinical Use ◽

Invasive Procedures ◽

Renin Angiotensin ◽

Current Review ◽

Adrenoceptor Agonists

The autonomic nervous system (ANS) and renin-angiotensin-aldosterone system (RAAS) are involved in many cardiovascular disorders, including pulmonary hypertension (PH). The current review focuses on the role of the ANS and RAAS activation in PH and updated evidence of potential therapies targeting both systems in this condition, particularly in Groups 1 and 2. State of the art knowledge in preclinical and clinical use of pharmacologic drugs (beta-blockers, beta-three adrenoceptor agonists, or renin-angiotensin-aldosterone signaling drugs) and invasive procedures, such as pulmonary artery denervation, is provided.

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COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa114 ◽

2020 ◽

Vol 75 (7) ◽

pp. 1667-1670 ◽

Cited By ~ 203

Author(s):

Dan Zhou ◽

Sheng-Ming Dai ◽

Qiang Tong

Keyword(s):

T Cell Activation ◽

Cell Activation ◽

Distress Syndrome ◽

Antiviral Effect ◽

Inhibitory Effect ◽

Clinical Use ◽

Cytokine Release ◽

Novel Coronavirus ◽

Effective Drugs ◽

Preventive Effects

Abstract A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide. The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release. There is an urgent need to identify safe and effective drugs for treatment. Chloroquine (CQ) exhibits a promising inhibitory effect. However, the clinical use of CQ can cause severe side effects. We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation. It has a safer clinical profile and is suitable for those who are pregnant. It is cheaper and more readily available in China. We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression.

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