scholarly journals Zebrafish as a Screening Model to Study the Single and Joint Effects of Antibiotics

2021 ◽  
Vol 14 (6) ◽  
pp. 578
Author(s):  
Roxana Jijie ◽  
Gabriela Mihalache ◽  
Ioana-Miruna Balmus ◽  
Stefan-Adrian Strungaru ◽  
Emanuel Stefan Baltag ◽  
...  
Keyword(s):  
Animal Model ◽  
Developmental Stages ◽  
Model Systems ◽  
In Vivo Studies ◽  
Research Papers ◽  
Vertebrate Model ◽  
Efficacy Assessment ◽  
Potential Impact ◽  
The Impact

The overuse of antibiotics combined with the limitation of wastewater facilities has resulted in drug residue accumulation in the natural environment. Thus, in recent years, the presence of antibiotic residues in the environment has raised concerns over the potential harmful effects on ecosystems and human health. The in vivo studies represent an essential step to study the potential impact induced by pharmaceutical exposure. Due to the limitations of traditional vertebrate model systems, zebrafish (Danio rerio) has recently emerged as a promising animal model to study the toxic effects of drugs and their therapeutic efficacy. The present review summarizes the recent advances made on the toxicity of seven representative classes of antibiotics, namely aminoglycosides, β-lactams, macrolides, quinolones, sulfonamides, tetracyclines and polyether antibiotics, in zebrafish, as well as the combined effects of antibiotic mixtures, to date. Despite a significant amount of the literature describing the impact of single antibiotic exposure, little information exists on the effects of antibiotic mixtures using zebrafish as an animal model. Most of the research papers on this topic have focused on antibiotic toxicity in zebrafish across different developmental stages rather than on their efficacy assessment.

scholarly journals Trends in Managing Cardiac and Orthopaedic Device-Associated Infections by Using Therapeutic Biomaterials

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1556
Author(s):  
Stefania Scialla ◽  
Giorgia Martuscelli ◽  
Francesco Nappi ◽  
Sanjeet Singh Avtaar Singh ◽  
Adelaide Iervolino ◽  
...  
Keyword(s):  
Clinical Medicine ◽  
Preventive Treatment ◽  
Active Surface ◽  
In Vivo Studies ◽  
Antibiotic Resistant ◽  
Implanted Medical Devices ◽  
Hospital Acquired ◽  
Systemic Antibiotics ◽  
The Impact

Over the years, there has been an increasing number of cardiac and orthopaedic implanted medical devices, which has caused an increased incidence of device-associated infections. The surfaces of these indwelling devices are preferred sites for the development of biofilms that are potentially lethal for patients. Device-related infections form a large proportion of hospital-acquired infections and have a bearing on both morbidity and mortality. Treatment of these infections is limited to the use of systemic antibiotics with invasive revision surgeries, which had implications on healthcare burdens. The purpose of this review is to describe the main causes that lead to the onset of infection, highlighting both the biological and clinical pathophysiology. Both passive and active surface treatments have been used in the field of biomaterials to reduce the impact of these infections. This includes the use of antimicrobial peptides and ionic liquids in the preventive treatment of antibiotic-resistant biofilms. Thus far, multiple in vivo studies have shown efficacious effects against the antibiotic-resistant biofilm. However, this has yet to materialize in clinical medicine.

67 Current Status and Future Prospective of the Use of Plant Bioactive Compounds in Dairy and Beef Cattle

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 132-132
Author(s):  
Sergio Calsamiglia ◽  
Maria Rodriguez-Prado ◽  
Gonzalo Fernandez-Turren ◽  
Lorena Castillejos
Keyword(s):  
Beef Cattle ◽  
Essential Oils ◽  
Average Daily Gain ◽  
Rumen Fermentation ◽  
Production Performance ◽  
In Vivo Studies ◽  
Current Status ◽  
The Impact

Abstract In the last 20 years there has been extensive in vitro research on the effects of plant extracts and essential oils on rumen microbial fermentation. The main objectives have been to improve energy metabolism through a reduction in methane emissions and an increase in propionate production; and to improve protein metabolism by reducing proteolysis and deamination. While the positive results from in vitro studies has stimulated the release of commercial products based on blends of essential oils, there is limited in vivo evidence on the rumen fermentation and production performance effects. A literature search was conducted to select in vivo studies where information on rumen fermentation and animal performance was reported. For dairy cattle, we identified 37 studies of which 21 were adequate to test production performance. Ten studies reported increases and 3 decreases in milk yield. For beef cattle, we identified 20 studies with rumen fermentation profile and 22 with performance data. Average daily gain improved in 7 and decreased in 1 study. Only 1 out of 16 studies reported an improvement in feed efficiency. Data indicate that out of more than 500 products tested in vitro, only around 20 have been tested in vivo in different mixtures and doses. The use of statistical approaches will allow to describe the conditions, doses and responses in dairy and beef cattle performance. The search for postruminal effects offers another alternative use. Evidence for effects on the intestinal and systemic effects on the immune system and antioxidant status (i.e., capsicum, garlic, eugenol, cinnamaldehyde curcuma, catechins, anethol or pinene), and in the modulation of metabolic regulation (capsicum, cinnamaldehyde, curcuma or garlic) may open the opportunity for future applications. However, stability of the product in the GI tract, description of the mechanisms of action and the impact of these changes on performance needs to be further demonstrated.

scholarly journals Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Quentin Vallé ◽  
Béatrice B. Roques ◽  
Alain Bousquet-Mélou ◽  
David Dahlhaus ◽  
Felipe Ramon-Portugal ◽  
...  
Keyword(s):  
Intestinal Content ◽  
Multidrug Resistant ◽  
Preclinical Model ◽  
Intestinal Contents ◽  
Potential Activity ◽  
Potential Impact ◽  
The Impact ◽  
Pharmacodynamic Approach

The increase of multidrug-resistant (MDR) bacteria has renewed interest in old antibiotics, such as minocycline, that can be active against various MDR Gram-negative pathogens. The elimination of minocycline by both kidneys and liver makes it suitable for impaired renal function patients. However, the drawback is the possible elimination of a high amount of drug in the intestines, with potential impact on the digestive microbiota during treatment. This study aimed to predict the potential activity of minocycline against Enterobacterales in the gut after parenteral administration, by combining in vivo and in vitro studies. Total minocycline concentrations were determined by UPLC-UV in the plasma and intestinal content of piglets following intravenous administration. In parallel, the in vitro activity of minocycline was assessed against two Escherichia coli strains in sterilized intestinal contents, and compared to activity in a standard broth. We found that minocycline concentrations were 6–39 times higher in intestinal contents than plasma. Furthermore, minocycline was 5- to 245-fold less active in large intestine content than in a standard broth. Using this PK-PD approach, we propose a preclinical pig model describing the link between systemic and gut exposure to minocycline, and exploring its activity against intestinal Enterobacterales by taking into account the impact of intestinal contents.

scholarly journals Monodelphis domestica as a fetal intra-cerebral inoculation model for Zika virus pathogenesis

2019 ◽  
Author(s):  
John M. Thomas ◽  
Juan Garcia ◽  
Matthew Terry ◽  
Ileana Lozano ◽  
Susan M. Mahaney ◽  
...  
Keyword(s):  
Animal Model ◽  
Zika Virus ◽  
Developmental Stages ◽  
Experimental Manipulation ◽  
Monodelphis Domestica ◽  
Growth Restriction ◽  
Human Embryos ◽  
New Model ◽  
Global Growth

ABSTRACTMonodelphis domestica, also known as the laboratory opossum, is a marsupial native to South America. At birth, these animals are developmentally equivalent to human embryos at approximately 5 weeks of gestation which, when coupled with other characteristics including the size of the animals, the development of a robust immune system during juvenile development, and the relative ease of experimental manipulation, have made M. domestica a valuable model in many areas of biomedical research. However, their suitability as models for infectious diseases, especially diseases caused by viruses such as Zika virus (ZIKV), is currently unknown. Here, we describe the replicative effects of ZIKV using a fetal intra-cerebral model of inoculation. Using immunohistochemistry and in situ hybridization, we found that opossum embryos and fetuses are susceptible to infection by ZIKV administered intra-cerebrally, that the infection persists long term, and that the infection and viral replication consistently results in neural pathology and may occasionally result in global growth restriction. These results demonstrate the utility of M. domestica as a new animal model for investigating ZIKV infection in vivo. This new model will facilitate further inquiry into viral pathogenesis, particularly for those viruses that are neurotropic, that may require a host with the ability to support sustained viral infection, and/or that may require intra-cerebral inoculations of large numbers of embryos or fetuses.AUTHOR SUMMARYHere we show that the laboratory opossum (Monodelphis domestica) is a valuable new model for studying Zika virus pathogenesis. Newborns are at the developmental stage of 5-week human embryos. Zika virus inoculated on a single occasion into the brains of pups at the human developmental stages of 8-20 weeks post conception replicated in neuronal cells and persisted as a chronic infection until the experimental endpoint at 74-days post infection. In addition, we observed global growth restriction in one of 16 inoculated animals; global growth restriction has been observed in humans and other animal models infected with Zika virus. The results illustrate great potential for this new animal model for high throughput research on the neurological effects of Zika virus infection of embryos and fetuses.

scholarly journals Impact of the Order of Initiation of Fluconazole and Amphotericin B in Sequential or Combination Therapy on Killing of Candida albicans In Vitro and in a Rabbit Model of Endocarditis and Pyelonephritis

2001 ◽  
Vol 45 (2) ◽  
pp. 485-494 ◽  
Author(s):  
Arnold Louie ◽  
Pamela Kaw ◽  
Partha Banerjee ◽  
Weiguo Liu ◽  
George Chen ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Induced Resistance ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Infection Model ◽  
Simultaneous Exposure ◽  
The Impact

ABSTRACT In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of Candida albicans to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of C. albicans to AMB and on the outcome. The contribution of FLC-induced resistance to AMB for C. albicans also was assessed. In vitro, AMB monotherapy rapidly killed each of four C. albicans strains; FLC alone was fungistatic. Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to >40 h. Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation. Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC→AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone. This antagonistic effect persisted for at least 24 h. Simultaneous exposure of C. albicans to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of ≥1 μg/ml; antagonism was seen using an AMB concentration of 0.5 μg/ml. The in vitro findings accurately predicted outcomes in our rabbit infection model. In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB→AMB+FLC) rapidly sterilized kidneys and cardiac vegetations. AMB+FLC(simult) and FLC→AMB treatments were slower in clearing fungi from infected tissues. FLC monotherapy and FLC→AMB+FLC were both fungistatic and were the least active regimens. No adverse interaction was observed between AMB and FLC for the AMB→FLC regimen. However, FLC→AMB treatment was slower than AMB alone in clearing fungi from tissues. Thus, our in vitro and in vivo studies both demonstrate that preexposure of C. albicans to FLC reduces fungal susceptibility to AMB. The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.

scholarly journals Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R

2018 ◽  
Vol 115 (27) ◽  
pp. E6135-E6144 ◽  
Author(s):  
Melika Sarem ◽  
Miriam Heizmann ◽  
Andrea Barbero ◽  
Ivan Martin ◽  
V. Prasad Shastri
Keyword(s):  
Endochondral Ossification ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
In Vivo Studies ◽  
Human Mscs ◽  
Down Regulation ◽  
Calcium Sensing ◽  
Biomimetic Apatite ◽  
The Impact

In adult bone injuries, periosteum-derived mesenchymal stem/stromal cells (MSCs) form bone via endochondral ossification (EO), whereas those from bone marrow (BM)/endosteum form bone primarily through intramembranous ossification (IMO). We hypothesized that this phenomenon is influenced by the proximity of MSCs residing in the BM to the trabecular bone microenvironment. Herein, we investigated the impact of the bone mineral phase on human BM-derived MSCs’ choice of ossification pathway, using a biomimetic bone-like hydroxyapatite (BBHAp) interface. BBHAp induced hyperstimulation of extracellular calcium-sensing receptor (CaSR) and temporal down-regulation of parathyroid hormone 1 receptor (PTH1R), leading to inhibition of chondrogenic differentiation of MSCs even in the presence of chondroinductive factors, such as transforming growth factor-β1 (TGF-β1). Interestingly rescuing PTH1R expression using human PTH fragment (1–34) partially restored chondrogenesis in the BBHAp environment. In vivo studies in an ectopic site revealed that the BBHAp interface inhibits EO and strictly promotes IMO. Furthermore, CaSR knockdown (CaSR KD) disrupted the bone-forming potential of MSCs irrespective of the absence or presence of the BBHAp interface. Our findings confirm the expression of CaSR in human BM-derived MSCs and unravel a prominent role for the interplay between CaSR and PTH1R in regulating MSC fate and the choice of pathway for bone formation.

scholarly journals Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies

2019 ◽  
Vol 20 (11) ◽  
pp. 2675 ◽  
Author(s):  
Nicholas Wilson ◽  
Robert Steadman ◽  
Ilaria Muller ◽  
Mohd Draman ◽  
D. Aled Rees ◽  
...  
Keyword(s):  
Stem Cell Differentiation ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Synthesis Inhibitor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inhibitory Role ◽  
The Impact

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity.

scholarly journals Exposure to airborne gold nanoparticles: a review of current toxicological data on the respiratory tract

2020 ◽  
Vol 22 (8) ◽  
Author(s):  
Barbara De Berardis ◽  
Magda Marchetti ◽  
Anna Risuglia ◽  
Federica Ietto ◽  
Carla Fanizza ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Human Health ◽  
Large Scale ◽  
Current Knowledge ◽  
Engineered Nanoparticles ◽  
In Vivo Studies ◽  
Field Exposure ◽  
The Impact

AbstractIn recent years, the introduction of innovative low-cost and large-scale processes for the synthesis of engineered nanoparticles with at least one dimension less than 100 nm has led to countless useful and extensive applications. In this context, gold nanoparticles stimulated a growing interest, due to their peculiar characteristics such as ease of synthesis, chemical stability and optical properties. This stirred the development of numerous applications especially in the biomedical field. Exposure of manufacturers and consumers to industrial products containing nanoparticles poses a potential risk to human health and the environment. Despite this, the precise mechanisms of nanomaterial toxicity have not yet been fully elucidated. It is well known that the three main routes of exposure to nanomaterials are by inhalation, ingestion and through the skin, with inhalation being the most common route of exposure to NPs in the workplace. To provide a complete picture of the impact of inhaled gold nanoparticles on human health, in this article, we review the current knowledge about the physico-chemical characteristics of this nanomaterial, in the size range of 1–100 nm, and its toxicity for pulmonary structures both in vitro and in vivo. Studies comparing the toxic effect of NPs larger than 100 nm (up to 250 nm) are also discussed.

scholarly journals Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 168 ◽  
Author(s):  
Margherita Falavigna ◽  
Paul Stein ◽  
Gøril Flaten ◽  
Massimiliano di Cagno
Keyword(s):  
Drug Interaction ◽  
Drug Absorption ◽  
Cost Effective ◽  
Physicochemical Characteristics ◽  
In Vivo Studies ◽  
Phospholipid Vesicle ◽  
Mucus Layer ◽  
The Impact

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

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