scholarly journals Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19

2020 ◽  
Author(s):  
Alexey Komissarov ◽  
Ivan Molodtsov ◽  
Oxana Ivanova ◽  
Elena Maryukhnich ◽  
Svetlana Kudryavtseva ◽  
...  
Keyword(s):  
Clinical Data ◽  
Mild Condition ◽  
Animal Studies ◽  
Pharmacological Therapy ◽  
Gradual Decrease ◽  
Mild Form ◽  
Model Animal

AbstractDue to the urgent need to stop the spread of the COVID-19 attempts to find the drug with anti SARS-CoV-2 effects among ones already available on a market are actively being made. A number of in vitro as well as in vivo model animal studies have shown that widely used compound hydroxychloroquine (HCQ) is able to cause anti-viral effect on SARS-CoV-2. While there is no enough clinical data to support the use of HCQ, several countries including Russia have already approved HCQ as treatment and prophylactic option. In the current study we analyzed the dynamics of the SARS-CoV-2 RNA quantity change in nasopharynx swabs of infected patients in mild condition and compared that of patients receiving HCQ and receiving no antiviral pharmacological therapy. We found that most of the patients demonstrated gradual decrease in the number of SARS-CoV-2 RNA copies in the swab regardless of the HCQ receiving. Noteworthy that patients with RNA load higher than 106 copies were hospitalized due to condition deteriorating significantly more frequently compared to those with RNA load below 106 copies even with HCQ administration. In addition, the results of the current study indicate that recovering patients may produce viruses at least during 18 days from the onset of symptoms and HCQ therapy does not block or reduce it.

scholarly journals High SARS-CoV-2 load in the nasopharynx of patients with a mild form of COVID-19 is associated with clinical deterioration regardless of the hydroxychloroquine administration

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246396
Author(s):  
Alexey Komissarov ◽  
Ivan Molodtsov ◽  
Oxana Ivanova ◽  
Elena Maryukhnich ◽  
Svetlana Kudryavtseva ◽  
...  
Keyword(s):  
Risk Factor ◽  
Pharmacological Therapy ◽  
Control Group ◽  
Mild Form ◽  
Treatment Protocols ◽  
Mild Disease ◽  
Viral Shedding ◽  
Virus Rna

Because of the constantly growing numbers of COVID-19 infections and deaths, attempts were undertaken to find drugs with anti-SARS-CoV-2 activity among ones already approved for other pathologies. In the framework of such attempts, in a number of in vitro, as well as in vivo, models it was shown that hydroxychloroquine (HCQ) has an effect against SARS-CoV-2. While there were not enough clinical data to support the use of HCQ, several countries including Russia have included HCQ in treatment protocols for infected patients and for prophylaxis. In the current non-randomized, observational study we evaluated the SARS-CoV-2 RNA in nasopharynx swabs from infected patients 7–10 days post symptoms with clinically mild disease and compared the viral RNA load dynamics between patients receiving HCQ (200 mg twice per day according to the Ministry of Health of Russian Federation treatment instructions, n = 33) and a control group without antiviral pharmacological therapy (n = 12). We found a statistically significant relationship between maximal RNA quantity and deterioration of patients’ medical conditions, and as well we confirmed arterial hypertension to be a risk factor for people with COVID-19. However, we showed that at the dose used in the study HCQ therapy neither shortened the viral shedding period nor reduced the virus RNA load.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Seminal Plasma: Relevant for Fertility?

2021 ◽  
Vol 22 (9) ◽  
pp. 4368
Author(s):  
Heriberto Rodriguez-Martinez ◽  
Emilio A. Martinez ◽  
Juan J. Calvete ◽  
Fernando J. Peña Vega ◽  
Jordi Roca
Keyword(s):  
Seminal Plasma ◽  
Current Knowledge ◽  
Inorganic Ions ◽  
Vitro Fertilization ◽  
Dna And Rna ◽  
Model Animal ◽  
Sexual Glands ◽  
Species Specific

Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.

scholarly journals Occupational Exposure to Carbon Nanotubes and Carbon Nanofibres: More Than a Cobweb

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 745
Author(s):  
Enrico Bergamaschi ◽  
Giacomo Garzaro ◽  
Georgia Wilson Jones ◽  
Martina Buglisi ◽  
Michele Caniglia ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Animal Studies ◽  
Chemical Properties ◽  
Biological Behavior ◽  
Cross Sectional ◽  
Carbon Nanofibres ◽  
Material Entity ◽  
Cross Sectional Design

Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are erroneously considered as singular material entities. Instead, they should be regarded as a heterogeneous class of materials bearing different properties eliciting peculiar biological outcomes both in vitro and in vivo. Given the pace at which the industrial production of CNTs/CNFs is increasing, it is becoming of utmost importance to acquire comprehensive knowledge regarding their biological activity and their hazardous effects in humans. Animal studies carried out by inhalation showed that some CNTs/CNFs species can cause deleterious effects such as inflammation and lung tissue remodeling. Their physico-chemical properties, biological behavior and biopersistence make them similar to asbestos fibers. Human studies suggest some mild effects in workers handling CNT/CNF. However, owing to their cross-sectional design, researchers have been as yet unable to firmly demonstrate a causal relationship between such an exposure and the observed effects. Estimation of acceptable exposure levels should warrant a proper risk management. The aim of this review is to challenge the conception of CNTs/CNFs as a single, unified material entity and prompt the establishment of standardized hazard and exposure assessment methodologies able to properly feeding risk assessment and management frameworks.

scholarly journals Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Animal Studies ◽  
Citrus Fruit ◽  
Epidemiological Studies ◽  
Personal Health ◽  
Current Review ◽  
Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

scholarly journals Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

1992 ◽  
Vol 3 (4) ◽  
pp. 193-201 ◽  
Author(s):  
George G Zhanel ◽  
Daryl J Hoban ◽  
Godfrey KM Harding
Keyword(s):  
Antimicrobial Activity ◽  
Animal Studies ◽  
Molecular Level ◽  
Bacterial Virulence ◽  
Antibacterial Effects ◽  
Wide Range ◽  
Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses

2005 ◽  
Vol 99 (4) ◽  
pp. 1582-1591 ◽  
Author(s):  
Donna R. Hill ◽  
Marianne E. Brunner ◽  
Deborah C. Schmitz ◽  
Catherine C. Davis ◽  
Janine A. Flood ◽  
...  
Keyword(s):  
Animal Studies ◽  
Pathogenic Bacteria ◽  
Sensor Technology ◽  
Atmospheric Conditions ◽  
Bacterial Virulence Factor ◽  
Carbon Dioxide Levels ◽  
Kinetics Of ◽  
Insertion Process

Previous in vitro and in vivo animal studies showed that O2and CO2concentrations can affect virulence of pathogenic bacteria such as Staphylococcus aureus. The objective of this work was to measure O2and CO2levels in the vaginal environment during tampon wear using newly available sensor technology. Measurements by two vaginal sensors showed a decrease in vaginal O2levels after tampon insertion. These decreases were independent of the type of tampons used and the time of measurement (mid-cycle or during menstruation). These results are not in agreement with a previous study that concluded that oxygenation of the vaginal environment during tampon use occurred via delivery of a bolus of O2during the insertion process. Our measurements of gas levels in menses showed the presence of both O2and CO2in menses. The tampons inserted into the vagina contained O2and CO2levels consistent with atmospheric conditions. Over time during tampon use, levels of O2in the tampon decreased and levels of CO2increased. Tampon absorbent capacity, menses loading, and wear time influenced the kinetics of these changes. Colonization with S. aureus had no effect on the gas profiles during menstruation. Taken collectively, these findings have important implications on the current understanding of gaseous changes in the vaginal environment during menstruation and the potential role(s) they may play in affecting bacterial virulence factor production.

scholarly journals Bisphosphonates: from preclinical evidence to survival data in the oncologic setting

2011 ◽  
pp. 141-151
Author(s):  
Daniele Santini ◽  
Maria Elisabetta Fratto ◽  
Bruno Vincenzi ◽  
Silvia Angeletti ◽  
Giordano Dicuonzo ◽  
...  
Keyword(s):  
Clinical Data ◽  
Survival Data ◽  
Clinical Evidence ◽  
Bisphosphonate Therapy ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Skeletal Disease

Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. In vivo pre-clinical data suggest that bisphosphonates may exert an antitumor effect and preliminary clinical data show promising activity on metastatic disease in cancer patients. This review will describe the pre-clinical evidence of action of bisphosphonates on osteoclasts and tumor cells, in both in vitro and animal models. In addition, the effects of principal bisphosphonates on skeletal disease progression in patients with cancers in different sites, including breast cancer, prostate cancer and non-small cell lung cancer will be reported. The preliminary clinical data from retrospective trials on the effect of bisphosphonates on survival will be described and the ongoing adjuvant phase III trial will be analyzed. This review will describe the preliminary clinical evidences from prospective studies on the effect of zoledronic acid treatment on the prevention of bone metastases.

scholarly journals Assessment of In Vitro and In Vivo Bioremediation Potentials of Orally Supplemented Free and Microencapsulated Lactobacillus acidophilus KLDS Strains to Mitigate the Chronic Lead Toxicity

2021 ◽  
Vol 9 ◽  
Author(s):  
Zafarullah Muhammad ◽  
Rabia Ramzan ◽  
Ruifen Zhang ◽  
Dong Zhao ◽  
Mehak Gul ◽  
...  
Keyword(s):  
Lactobacillus Acidophilus ◽  
Lead Toxicity ◽  
Significant Protection ◽  
Serum Enzyme ◽  
Freundlich Model ◽  
Model Animal ◽  
Amino Amide ◽  
And Oxidative Stress

Lead (Pb) is a pestilent and relatively nonbiodegradable heavy metal, which causes severe health effects by inducing inflammation and oxidative stress in animal and human tissues. This is because of its significant tolerance and capability to bind Pb (430 mg/L) and thermodynamic fitness to sequester Pb in the Freundlich model (R2 = 0.98421) in vitro. Lactobacillus acidophilus KLDS1.1003 was selected for further in vivo study both in free and maize resistant starch (MRS)–based microencapsulated forms to assess its bioremediation aptitude against chronic Pb lethality using adult female BALB/c mice as a model animal. Orally administered free and microencapsulated KLDS 1.1003 provided significant protection by reducing Pb levels in the blood (127.92 ± 5.220 and 101.47 ± 4.142 µg/L), kidneys (19.86 ± 0.810 and 18.02 ± 0.735 µg/g), and liver (7.27 ± 0.296 and 6.42 ± 0.262 µg/g). MRS-microencapsulated KLDS 1.0344 improved the antioxidant index and inhibited changes in blood and serum enzyme concentrations and relieved the Pb-induced renal and hepatic pathological damages. SEM and EDS microscopy showed that the Pb covered the surfaces of cells and was chiefly bound due to the involvement of the carbon and oxygen elements. Similarly, FTIR showed that the amino, amide, phosphoryl, carboxyl, and hydroxyl functional groups of bacteria and MRS were mainly involved in Pb biosorption. Based on these findings, free and microencapsulated L. acidophilus KLDS 1.0344 could be considered a potential dietetic stratagem in alleviating chronic Pb toxicity.

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