43 research outputs found
Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review)
The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID‑19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID‑19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts
A new threat from an old enemy: Re‑emergence of coronavirus (Review)
The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus‑associated disease, the spread and lethality of the 2019 outbreak (COVID‑19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale
A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse
Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming
Beta 1, Beta 2 and Beta 3 Adrenergic Receptor Gene Polymorphisms in a Southeastern European Population
Genetic polymorphisms in β1-, β2- and β3-adrenergic receptors (β-ARs) have been associated with chronic non-communicable disorders, such as cardiovascular diseases, asthma, chronic obstructive pulmonary disease (COPD) and obesity, as well as β-agonists and antagonists response and toxicity. The purpose of this study was to determine the frequency distribution of ADRB1 genetic variants Ser49Gly and Arg389Gly, ADRB2 variants Gly16Arg and Gln27Glu, ADRB3 variant Trp64Arg in a Southeastern European Caucasian (SEC) population sample and to establish a comparison with existing data from other human populations. A sample of 431 men and 590 women volunteered to participate in this genotyping analysis after anonymization and de-identification. Real Time PCR (Melting Curve Analysis) followed DNA extraction from buccal swabs and statistical analysis of the results was performed. The allele frequencies in the SEC population were Ser49 (90.3%), Arg389 (69.49%), Gly16 (61.61%), Gln27 (65.72%), and Trp64 (94.52%), while a Hardy-Weinberg Equilibrium (HWE) was detected in the population studied. Comparisons for the Ser49Gly, Gln27Glu, and Trp64Arg allele distributions demonstrated significant differences between SEC and the European group. European subgroups comparisons showed that allele distributions were similar for four of the five SNPs between SEC and Southwestern European Caucasians (SWC), while they were quite distinct from the Northwestern European Caucasians (NWC). These data underline the importance of interethnic variability of β-ARs genetic polymorphisms
Kinetics of progenitor hemopoetic stem cells in sepsis: Correlation with patients survival?
BACKGROUND: Current theories underline the crucial role of pro-inflammatory mediators produced by monocytes for the pathogenesis of sepsis. Since monocytes derive from progenitor hemopoetic cells, the kinetics of stem cells was studied in peripheral blood of patients with sepsis. METHODS: Blood was sampled from 44 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 upon initiation of symptoms. Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8 and G-CSF were estimated by ELISA. CD34/CD45 cells were determined after incubation with anti-CD45 FITC and anti-CD34 PE monocloncal antibodies and flow cytometric analysis. Samples from eight healthy volunteers served as controls. RESULTS: Median of CD34/CD45 absolute count of controls was 1.0/μl. Respective values of the total study population were 123.4, 112.4, 121.5 and 120.9/μl on days 1, 3, 5 and 7 (p < 0.0001 compared to controls). Positive correlations were found between the absolute CD34/CD45 count and the absolute monocyte count on days 1, 5 and 7. Survival was prolonged among patients with less than 310/μl CD34/CD45 cells on day 1 compared to those with more than 310/μl of CD34/CD45 cells (p: 0.022). Hazard ratio for death due to sepsis was 5.47 (p: 0.039) for CD34/CD45 cells more than 310/μl. Median IL-6 on day 1 was 56.78 and 233.85 pg/ml respectively for patients with less than 310/μl and more than 310/μl CD34/CD45 cells (p: 0.021). CONCLUSION: Stem cells are increased in peripheral blood over all days of follow-up compared to healthy volunteers. Patients with counts on day 1 less than 310/μl are accompanied by increased survival compared to patients with more than 310/μl
HUMAN4D: A human-centric multimodal dataset for motions and immersive media
We introduce HUMAN4D, a large and multimodal 4D dataset that contains a variety of human activities simultaneously captured by a professional marker-based MoCap, a volumetric capture and an audio recording system. By capturing 2 female and 2 male professional actors performing vari
Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort
BACKGROUND:
Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice.
METHODS:
A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively.
RESULTS:
SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655.
CONCLUSIONS:
In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin
Η ΣΥΧΝΟΤΗΤΑ ΚΑΤΑΝΟΜΗΣ ΤΟΥ ΑΡΓΟΥ ΚΑΙ ΓΡΗΓΟΡΟΥ ΦΑΙΝΟΤΥΠΟΥ ΑΚΕΤΥΛΙΩΣΗΣ ΣΕ ΑΣΘΕΝΕΙΣ ΜΕ ΚΑΡΚΙΝΟ ΤΟΥ ΣΤΟΜΑΧΟΥ
Morphological characteristics of magnetic particles and their environmental impact: The case of Sarigiol basin (Greece)
Magnetic particles were separated from soil and sediment samples from the Sarigiol basin in northwestern Greece in order to study their morphological characteristics with scanning electron microscopy. They appear in the form of octahedrons and spheres and they have lithogenic and anthropogenic source, respectively. The source of the lithogenic magnetic particles is the ophiolite complexes at the NE and SW part of the basin while the fly ash and its dispersion from the two power plants located in the research area is the source of the anthropogenic magnetic particles. The surface structure of magnetic particles is either simple or more complex while the average size of the spheres is 10-50 μm. Highest values of the ratio of the anthropogenic to lithogenic magnetic particles at the NE and locally at the NW, N and SW part of the study area are a strong evidence of the environmental footprint that anthropogenic activities have at the upper soil horizons of the Sarigiol basin
Exploration of vascular adhesion protein-1 expression in patients with conjunctivitis associated systemic lupus erythematosus using 2D-DIGE
Conjunctivitis associated systemic lupus erythematosus (caSLE) is a
connective tissue autoimmune disease with a large spectrum of clinical
manifestations. The disease may lead to ocular complications and in
severe cases may be sight-threatening. This study investigated the
expression of vascular adhesion protein-1 (VAP-1) in SLE patients with
conjunctivitis and the relationship between VAP-1 and other proteins in
the onset of the disease. Ten patients with caSLE (caSLE group) and 10
healthy volunteers (control group) were enrolled in the study, in order
to evaluate the VAP-1 expression levels in blood. Protein expression
profiling was performed with two-dimensional fluorescence difference gel
electrophoresis (2D-DIGE) and analyzed with matrix-assisted laser
desorption/deionization time-of-flight (MALDI-TOF) used in tandem with
mass spectrometry. In the caSLE group, 8 proteins were expressed
differenty compared with the control group: C-reactive protein,
hemoglobin subunit beta, VAP-1, A-albumin (AFAM), enolase and
immunoglobulin heavy constant mu were upregulated; interferon regulatory
factor-1 and serum amyloid A2 protein were downregulated. Western
blotting results are consistent with the proteomics results, showing
that in caSLE group VAP-1 expression is increased in comparison to the
control group. VAP-1 protein participates in the inflammatory reaction
in the form of amine oxidase, copper containing 3. Bioinformatics
analysis suggested that VAP-1 protein could be used as a candidate
protein for further study regarding its role as a potential protein
marker for screening and effectively monitoring caSLE