scholarly journals Remdesivir: A Closer Look at Its Effect in COVID-19 Pandemic

Pharmacology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Huda R. Taha ◽  
Nour Keewan ◽  
Farah Slati ◽  
Nour A. Al-Sawalha
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Clinical Evidence ◽  
High Selectivity ◽  
Lavage Fluid ◽  
In Vivo Studies ◽  
Nucleotide Analog ◽  
Positive Results ◽  
Adenosine Nucleotide

<b><i>Background:</i></b> The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide. <b><i>Summary:</i></b> Remdesivir, a prodrug of adenosine nucleotide analog, is an antiviral with a broad spectrum of activity that was tested on SARS and Middle East respiratory syndrome infections. In vitro studies conducted on SARS-CoV-2 revealed that remdesivir inhibited viral replication with high selectivity index in cell cultures. In vivo studies showed that remdesivir reduced viral load in bronchoalveolar lavage fluid and attenuated pulmonary infiltrates in infected animals. Further, remdesivir showed promising results in terms of clinical improvement, shortening the recovery time, mortality rate, and the duration of oxygen need, despite that some clinical trials did not reveal significant effect on remdesivir use. Several studies showed positive results of remdesivir against the new variants. <b><i>Key Messages:</i></b> Remdesivir showed a promising beneficial effect against new variants of SARS-CoV-2, but more clinical evidence is needed to confirm this effect.

scholarly journals Behavior of Mesenchymal Stem Cells Obtained From Dental Tissues: A Review of the Literature

2019 ◽  
Vol 21 (1) ◽  
pp. 31-40
Author(s):  
Mariné Ortiz-Magdaleno DDS, MSc, PhD ◽  
Ana Isabel Romo-Tobías DDS ◽  
Fernando Romo-Ramírez DDS, MSc ◽  
Diana María Escobar DDS, MSc, PhD ◽  
Héctor Flores-Reyes DDS, MSc, PhD ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Evidence ◽  
Periodontal Regeneration ◽  
In Vivo Studies ◽  
Specific Cell ◽  
Key Factors ◽  
Dental Tissues

The success of tissue engineering in combination with tissue regeneration depends on the behavior and cellular activity in the biological processes developed within a structure that functions as a support, better known as scaffolds, or directly at the site of the injury. The cell-cell and cell-biomaterial interaction are key factors for the induction of a specific cell behavior, together with the bioactive factors that allow the formation of the desired tissue. Mesenchymal Stem Cells (MSC) can be isolated from the umbilical cord and bone marrow; however, the behavior of Dental Pulp Stem Cells (DPSC) has been shown to have a high potential for the formation of bone tissue, and these cells have even been able to induce the process of angiogenesis. Advances in periodontal regeneration, dentin-pulp complex, and craniofacial bone defects through the induction of MSC obtained from tooth structures in in vitro-in vivo studies have permitted the obtaining of clinical evidence of the achievements obtained to date.

scholarly journals Effects of Roflumilast, Selective PDE4 Inhibitor, on Airway Reactivity in Ovalbumin-Sensitized Guinea Pigs

2015 ◽  
Vol 5 (1) ◽  
pp. 12-19
Author(s):  
Nirmathan Tharmalingam ◽  
I. Medvedova ◽  
A. Eichlerova ◽  
M. Prso ◽  
D. Mokra ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Whole Body ◽  
Pde4 Inhibitor ◽  
Airway Reactivity

Abstract Background: Roflumilast as a phosphodiesterase 4 inhibitor has shown to increase lung functions and decrease the number of exacerbations in chronic obstructive lung disease. In this study, its ability to decrease the airway hyperresponsiveness in a model of eosinophil inflammation was evaluated. Methods: Healthy adult male guinea pigs were divided into groups as follows: the first group was considered as a healthy control group (without sensitization and therapy), animals in the second group were sensitized with ovalbumin, but left without further treatment, and the animals in the third group were sensitized with ovalbumin and treated with roflumilast perorally for 7 consecutive days. In vivo airway reactivity was evaluated using double-chamber whole body plethysmograph and measuring the specific airway resistance after nebulization of histamine aerosol. In vitro experiments were performed with tissue strips of trachea and lungs in organ bath, where their contractile responses to cumulative doses of acetylcholine and histamine were registered. The numbers of inflammatory cells in blood and bronchoalveolar lavage fluid were measured using standard staining. Results: Guinea pigs with roflumilast treatment showed decreased in vivo and in vitro airway reactivity associated with suppressed recruitment of inflammatory cells (especially eosinophils) in blood and bronchoalveolar lavage fluid. Conclusion: Roflumilast has demonstrated the therapeutic potential in the model of ovalbumin induced eosinophil inflammation typically present in patients with bronchial asthma.

Immunoregulatory effects of regulated, lung-targeted expression of IL-10 in vivo

2005 ◽  
Vol 288 (2) ◽  
pp. L251-L265 ◽  
Author(s):  
Donn Spight ◽  
Bin Zhao ◽  
Michael Haas ◽  
Susan Wert ◽  
Alvin Denenberg ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Targeted Expression ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Regulation of pulmonary inflammation involves an intricate balance of both pro- and anti-inflammatory mediators. Acute lung injury can result from direct pulmonary insults that activate alveolar macrophages to respond with increased cytokine expression. Such cytokine gene expression is mediated in part via NF-κB. IL-10 has been previously identified as an important endogenous anti-inflammatory cytokine in vivo on the basis of inhibiting NF-κB activation; however, the mechanism of this inhibition remains incompletely defined. We hypothesized that IL-10 regulated NF-κB activation in vivo via IκK inhibition. A bitransgenic mouse that allowed for externally regulated, lung-specific human IL-10 overexpression was generated. In the bitransgenic mice, introduction of doxycycline induced lung-specific, human IL-10 overexpression. Acute induction of IL-10 resulted in significant decreases in bronchoalveolar lavage fluid neutrophils (48%, P = 0.03) and TNF (62%, P < 0.01) following intratracheal LPS compared with bitransgenic negative mice. In vitro kinase assays showed this decrease to correlate to diminished lung IκK activity. Furthermore, we also examined the effect of chronic IL-10 overexpression in these transgenic mice. Results show that IL-10 overexpression in lungs of mature mice increased the number of intrapulmonary cells the phenotype of which was skewed toward increased B220+/CD45+ B cells and CD4+ T cells and was associated with increased CC chemokine expression. Thus regulated, lung-specific IL-10 overexpression may have a variety of complex immunologic effects depending on the timing and duration of expression.

Time to Shift: From Scaling and Root Planing to Root Surface Debridement

2014 ◽  
Vol 3 (3) ◽  
pp. 38-42 ◽  
Author(s):  
Marilou Ciantar
Keyword(s):  
Clinical Evidence ◽  
Root Surface ◽  
In Vivo Studies ◽  
Scaling And Root Planing ◽  
Periodontal Health ◽  
Dental Biofilm ◽  
Root Planing ◽  
Bacterial Plaque

Non-surgical periodontal treatment has traditionally been based on the notion that bacterial plaque (dental biofilm) penetrates and infects dental cementum. Removal of this infected cementum via scaling and root planing (SRP) was considered essential for re-establishing periodontal health. In the 1980s the concept of SRP was questioned because several in vitro studies showed that the biofilm was superficially located on the root surface and its disruption and removal could be relatively easily achieved by ultrasonic instrumentation of the root surface (known as root surface debridement (RSD). Subsequent in vivo studies corroborated the in vitro findings. There is now sufficient clinical evidence to substantiate the concept that the deliberate removal of cementum by SRP is no longer warranted or justified, and that the more gentle and conservative approach of RSD should be implemented in daily periodontal practice.

Long-Lasting Production of TGF-β1 by Alveolar Macrophages Exposed to Low Doses of Asbestos without Apoptosis

2007 ◽  
Vol 20 (4) ◽  
pp. 661-671 ◽  
Author(s):  
Y. Nishimura ◽  
T. Nishiike-Wada ◽  
Y. Wada ◽  
Y. Miura ◽  
T. Otsuki ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Tnf Α ◽  
Pulmonary Cells ◽  
Low Exposure ◽  
The Relationship ◽  
Tgf Β1

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-α, which induces the production of TGF-β1, leading to lung fibrogenesis. The present study examines the production of TGF-β1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-β1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid (B ALF) 1 day after the instillation, followed by increases in TGF-β1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-β1 in culture compared to those from the control rats. The addition of 2.5 μg/cm2 of CH augmented the production of TGF-β1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 μg/cm2 of CH, but was drastically induced at over 12.5 μg/cm2. In contrast, the production of TGF-β1 by AMs peaked at around 2.5 μg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-β1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-β1 may contribute not only to lung fibrosis but also to immune suppression.

scholarly journals In Vitro and In Vivo Efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae

2001 ◽  
Vol 45 (1) ◽  
pp. 312-315 ◽  
Author(s):  
Masahiro Takahata ◽  
Masako Shimakura ◽  
Ritsuko Hori ◽  
Kazuo Kizawa ◽  
Yozo Todo ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycoplasma Pneumoniae ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
In Vitro Activity ◽  
Free Base ◽  
Once Daily ◽  
Viable Cells

ABSTRACT T-3811, the free base of T-3811ME (BMS-284756), a new des-F(6)-quinolone, showed a potent in vitro activity (MIC at which 90% of the isolates tested are inhibited [MIC90], 0.0313 μg/ml) against Mycoplasma pneumoniae. The MIC90 of T-3811 was 4-fold higher than that of clarithromycin but was 4- to 8-fold lower than those of trovafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin and was 16- to 32-fold lower than those of levofloxacin, ciprofloxacin, and minocycline. In an experimental M. pneumoniae pneumonia model in hamsters, after the administration of T-3811ME (20 mg/kg of body weight as T-3811, once daily, orally) for 5 days, the reduction of viable cells of M. pneumoniae in bronchoalveolar lavage fluid was greater than those of trovafloxacin, levofloxacin, and clarithromycin (20 and 40 mg/kg, orally) (P < 0.05).

scholarly journals Development and Optimization of Chitosan Nanoparticle-Based Intranasal Vaccine Carrier

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 204
Author(s):  
Xiaoyi Gao ◽  
Nan Liu ◽  
Zengming Wang ◽  
Jing Gao ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Chitosan Nanoparticles ◽  
Vaccine Delivery ◽  
Lavage Fluid ◽  
In Vivo Studies ◽  
Modified Chitosan ◽  
Chitosan Nanoparticle ◽  
Low Toxicity ◽  
Intranasal Vaccine

Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.

scholarly journals Evidence That the Anti-Inflammatory Effect of Rubiadin-1-methyl Ether Has an Immunomodulatory Context

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Eduarda Talita Bramorski Mohr ◽  
Marcus Vinicius Pereira dos Santos Nascimento ◽  
Júlia Salvan da Rosa ◽  
Guilherme Nicácio Vieira ◽  
Iara Fabricia Kretzer ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Methyl Ether ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Inflammatory Parameters ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Background. In spite of the latest therapeutic developments, no effective treatments for handling critical conditions such as acute lung injuries have yet been found. Such conditions, which may result from lung infections, sepsis, multiple trauma, or shock, represent a significant challenge in intensive care medicine. Seeking ways to better deal with this challenge, the scientific community has recently devoted much attention to small molecules derived from natural products with anti-inflammatory and immunomodulatory effects. Aims. In this context, we investigated the anti-inflammatory effect of Rubiadin-1-methyl ether isolated from Pentas schimperi, using an in vitro model of RAW 264.7 macrophages induced by LPS and an in vivo model of acute lung injury (ALI) induced by LPS. Methods. The macrophages were pretreated with the compound and induced by LPS (1 μg/mL). After 24 h, using the supernatant, we evaluated the cytotoxicity, NOx, and IL-6, IL-1β, and TNF-α levels, as well as the effect of the compound on macrophage apoptosis. Next, the compound was administered in mice with acute lung injury (ALI) induced by LPS (5 mg/kg), and the pro- and anti-inflammatory parameters were analyzed after 12 h using the bronchoalveolar lavage fluid (BALF). Results. Rubiadin-1-methyl ether was able to inhibit the pro-inflammatory parameters studied in the in vitro assays (NOx, IL-6, and IL-1β) and, at the same time, increased the macrophage apoptosis rate. In the in vivo experiments, this compound was capable of decreasing leukocyte infiltration; fluid leakage; NOx; IL-6, IL-12p70, IFN-γ, TNF-α, and MCP-1 levels; and MPO activity. In addition, Rubiadin-1-methyl ether increased the IL-10 levels in the bronchoalveolar lavage fluid (BALF). Conclusions. These findings support the evidence that Rubiadin-1-methyl ether has important anti-inflammatory activity, with evidence of an immunomodulatory effect.

scholarly journals Cannabidiol—from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer

2019 ◽  
Vol 20 (23) ◽  
pp. 5905 ◽  
Author(s):  
Brigitta Kis ◽  
Feng Chen Ifrim ◽  
Valentina Buda ◽  
Stefana Avram ◽  
Ioana Zinuca Pavel ◽  
...  
Keyword(s):  
Seed Oil ◽  
Clinical Evidence ◽  
Cannabis Sativa ◽  
In Vivo Studies ◽  
Anticancer Effects ◽  
Different Types ◽  
Psychoactive Effects ◽  
Target Effects

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

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