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12
From Paper: Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study
Authors: Hoertel, Nicolas, et al
Published: Feb 2021
From Paper: Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study
Authors: Hoertel, Nicolas, et al
Published: Feb 2021
A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43–0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.
8
From Paper: Cardiovascular damage associated with subchronic exposure to the glyphosate herbicide in Wistar rats
Published: Feb 2021
From Paper: Cardiovascular damage associated with subchronic exposure to the glyphosate herbicide in Wistar rats
Published: Feb 2021
Glyphosate is the most widely used herbicide in the world. Although some studies have shown cardiac electrophysiological changes associated to glyphosate, the histopathological changes that this herbicide may cause in the cardiovascular system are not yet established. The aim of this study was to evaluate the cardiovascular effects of subchronic oral and inhalation exposure to the glyphosate herbicide in rats. Eighty albino Wistar rats were distributed into eight groups (five males and five females/group): inhalation control: nebulization with sodium chloride solution (NaCl); oral control: nebulized feed with NaCl; low inhalation concentration: nebulization with 3.71 × 10 −3 grams of active ingredient per hectare (g.a.i./ha) of glyphosate; low oral concentration: nebulized feed with 3.71 × 10 −3 g.a.i./ha of glyphosate; medium inhalation concentration: nebulization with 6.19 × 10 −3 g.a.i./ha of glyphosate; medium oral concentration: nebulized feed with 6.19 × 10 −3 g.a.i./ha of glyphosate; high inhalation concentration: nebulization with 9.28 × 10 −3 g.a.i./ha of glyphosate; and high oral concentration: nebulized feed with 9.28 × 10 −3 g.a.i./ha of glyphosate. After 75 days of exposure, the animals were euthanized, and aortas and hearts were collected for histopathological analysis. Fatty streaks were observed in most animals exposed to glyphosate and were more prevalent in male rats, regardless of the route of exposure ( p < 0.05). There were no differences in the measurements of the thickness of the right and left ventricle or in the collagen density of both ventricles in any of the groups evaluated ( p > 0.05). Our study suggests that glyphosate has atherogenic potential, regardless of the concentration and route of exposure.
1
Authors: Sun, Jiaojiao, et al
Published: Feb 2021
Authors: Sun, Jiaojiao, et al
Published: Feb 2021
The widespread use of silver nanoparticles (AgNPs), their many sources for human exposure, and the ability of AgNPs to enter organisms and induce general toxicological responses have raised concerns regarding their public health and environmental safety. To elucidate the differential toxic effects of polyvinylpyrrolidone-capped AgNPs with different primary particle sizes (i.e. 5, 50, and 75 nm), we performed a battery of cytotoxicity and genotoxicity assays and examined the inflammatory responses in two human cell lines (i.e. HepG2 and A549). Concentration-dependent decreases in cell proliferation and mitochondrial membrane potential and increases in cytokine (i.e. interleukin-6 and interleukin-8) excretion indicated disruption of mitochondrial function and inflammation as the main mediating factors of AgNPs-induced cytotoxicity. An incremental increase in genotoxicity with decreasing AgNPs diameter was noted in HepG2 cells, which was associated with S and G2/M accumulation and transcriptional activation of the GADD45α promoter as reflected by luciferase activity. Dose-related genetic damage, as indicated by Olive tail moment and micronucleus formation, was also observed in A549 cells, but these effects as well as the AgNPs-induced cytotoxicity were more associated with ionic Ag release from nanoparticles (NPs). In summary, the present study addressed different toxicity mechanisms of AgNPs, depending on the cell model, toxicological endpoint, particle size, and degree of Ag + release from NPs. The results suggest that the GADD45α promoter-driven luciferase reporter cell system provided a rapid screening tool for the identification of genotoxic properties of NPs across a range of different sizes and concentrations.
1
Authors: Neumann, Joachim, et al
Published: Feb 2021
Authors: Neumann, Joachim, et al
Published: Feb 2021
Abstract We have previously shown that histamine (2-(1 H -imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H 2 R-TG) mice that overexpress the human H 2 histamine receptor (H 2 R) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on H 2 Rs. Here, we wanted to determine whether the histamine effects in H 2 R-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from H 2 R-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM–10 μM) to higher concentrations (rightward shift) in left atrial preparations from H 2 R-TG. Similarly, in isolated perfused hearts from H 2 R-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the H 2 R-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from H 2 R-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at H 2 Rs in H 2 R-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline.
1
Authors: Yang, Yuming, et al
Published: Feb 2021
Authors: Yang, Yuming, et al
Published: Feb 2021
Abstract Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine. Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group. Conclusions The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
1
Authors: Nesma M Fahmy, Adel M Michael
Published: Feb 2021
Authors: Nesma M Fahmy, Adel M Michael
Published: Feb 2021
Abstract Background Modern built-in spectrophotometer's software supporting mathematical processes was a solution for increasing the selectivity for multicomponent in mixture. Objective Simultaneous spectrophotometric determination of the three naturally occurring antioxidants; rutin, hesperidin, and ascorbic acid in bulk forms and combined pharmaceutical formulation. Methods This was achieved by factorized zero order method (FZM), factorized derivative method (FD1M), and factorized derivative ratio method (FDRM); coupled with spectrum subtraction. Results Mathematical filtration techniques allowed each component to be obtained separately in either its zero, first, or derivative ratio form, thus allowed getting spectra typical to the pure components present in Vitamin C Forte® tablets. The proposed methods were applied over a concentration range of 2–50, 2–30, and 10–100 µg/mL for rutin, hesperidin, and ascorbic acid; respectively. Conclusion Recent methods for the analysis of binary mixtures as FZM and FD1M were successfully applied for the analysis of ternary mixtures and compared to the novel FDRM and all revealed to be specific and sensitive with successful application on their pharmaceutical formulation. Validation parameters were evaluated in accordance with the ICH guidelines. Statistical results were satisfactory revealing no significant difference regarding accuracy and precision. Highlights Factorized methods were able to resolve spectra identical to those of pure drugs present in mixture. Overlapped spectra of ternary mixtures could be resolved by SS-FDRM or by successive application of FZM and FDM.
1
Authors: Navya Sree K S, Swapnil J Dengale, Srinivas Mutalik, Krishnamurthy Bhat
Published: Feb 2021
Authors: Navya Sree K S, Swapnil J Dengale, Srinivas Mutalik, Krishnamurthy Bhat
Published: Feb 2021
Abstract Background Dronedarone HCl is an anti-arrhythmic drug indicated for atrial fibrillation. Dronedarone HCl(DRN) has a low solubility of 2 µg/mL and 4% bioavailability, thus it is formulated as co-amorphous system to enhance its solubility by using Quercetin(QCT) as coformer. Literature lacks a sensitive, accurate and economic method for simultaneous quantification of DRN and QCT in formulation. Objective To develop a RP-HPLC method for simultaneous estimation of DRN and QCT in DRN-QCT co-amorphous system. Method Co-amorphous system was prepared using solvent evaporation technique using DRN and QCT in 1:1 molar ratio. The separation was achieved on Purospher® STAR C18 (250 mm × 4.6 mm × 5 μm) column with mobile phase comprising of Acetonitrile and 25 mM phosphate buffer pH 3.6 (60:40, % v/v). Results DRN and QCT retained at 6.7 and 3.5 min, respectively. For both molecules, method was developed with a wide linearity range of 0.2–500 µg/mL. LOD for DRN was found to be 0.0013 and 0.0026 µg/mL for QCT. Also, LOQ for DRN was found to be 0.0041 and 0.0078 µg/mL for QCT. Conclusion Method was validated as per ICHQ2R1 guidelines for linearity, precision, accuracy, and robustness. The method was used in simultaneous quantification of DRN and QCT in co-amorphous samples. Highlights The method developed was used for the analysis of content uniformity and solubility samples of co-amorphous system, where the method was able to successfully quantify DRN and QCT. Low detection and quantification limits contribute to sensitivity of the method and wide linearity range assures the robust and precise quantification of molecules.
1
Authors: Edogbanya, Jacob, et al
Published: Feb 2021
Authors: Edogbanya, Jacob, et al
Published: Feb 2021
Abstract The C1ORF112 gene initially drew attention when it was found to be strongly co‐expressed with several genes previously associated with cancer and implicated in DNA repair and cell cycle regulation, such as RAD51 and the BRCA genes. The molecular functions of C1ORF112 remain poorly understood, yet several studies have uncovered clues as to its potential functions. Here, we review the current knowledge on C1ORF112 biology, its evolutionary history, possible functions, and its potential relevance to cancer. C1ORF112 is conserved throughout eukaryotes, from plants to humans, and is very highly conserved in primates. Protein models suggest that C1ORF112 is an alpha-helical protein. Interestingly, homozygous knockout mice are not viable, suggesting an essential role for C1ORF112 in mammalian development. Gene expression data show that, among human tissues, C1ORF112 is highly expressed in the testes and overexpressed in various cancers when compared to healthy tissues. C1ORF112 has also been shown to have altered levels of expression in some tumours with mutant TP53. Recent screens associate C1ORF112 with DNA replication and reveal possible links to DNA damage repair pathways, including the Fanconi anaemia pathway and homologous recombination. These insights provide important avenues for future research in our efforts to understand the functions and potential disease relevance of C1ORF112.
1
Authors: David Erskine, David Wood
Published: Feb 2021
Authors: David Erskine, David Wood
Published: Feb 2021
Abstract Topics for DTB review articles are selected by DTB’s editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.
1
Authors: Eileen D. Ward, Whitney A. Hopkins, Kayce Shealy
Published: Feb 2021
Authors: Eileen D. Ward, Whitney A. Hopkins, Kayce Shealy
Published: Feb 2021
Background: The American Diabetes Association (ADA) Diabetes Risk Test (DRT) is a screening tool to identify people at risk for developing diabetes. Individuals with a DRT score of 5 or higher may have prediabetes or diabetes and should see a healthcare provider. Objective: To determine how many additional employees are identified as being at risk for developing diabetes during an employee wellness screening by using a more stringent DRT cutoff score of 4 instead of 5. Methods: During an annual employee wellness screening event, a hemoglobin A1C (A1c) was drawn for participants with a DRT score of > 4 or by request regardless of risk score. A1C values were classified as normal (<5.7%), prediabetes (>5.7 and <6.5%) or diabetes (>6.5%). Risk scores and A1C values were analyzed using descriptive statistics. Cost of additional laboratory testing was also reviewed. Results: An A1C was collected for 158 participants. Fourteen of 50 (28%) participants with a DRT of 4 had A1c values in the prediabetes range and no history of diabetes or prediabetes. Using the lower DRT score of 4 resulted in an additional expenditure of $305 with $85.40 resulting in the identification of an otherwise unaware person at risk for developing diabetes. Conclusion: Using a DRT cutoff score of 4 as part of an employee wellness screening program resulted in additional laboratory costs to identify persons at risk for developing diabetes but also allowed for earlier education to slow or stop the progression to diabetes which may reduce healthcare costs over time.
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