The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials.

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Faculty Opinions recommendation of Simulation and prediction of in vivo drug metabolism in human populations from in vitro data.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091007.544382 ◽

2007 ◽

Author(s):

Marival Bermejo

Keyword(s):

Drug Metabolism ◽

Human Populations ◽

In Vivo Drug Metabolism ◽

Vitro Data ◽

In Vitro Data

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Transplantation of Adipose-derived Cells for Periodontal Regeneration: A Systematic Review

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666181105144430 ◽

2019 ◽

Vol 14 (6) ◽

pp. 504-518 ◽

Cited By ~ 3

Author(s):

Dilcele Silva Moreira Dziedzic ◽

Bassam Felipe Mogharbel ◽

Priscila Elias Ferreira ◽

Ana Carolina Irioda ◽

Katherine Athayde Teixeira de Carvalho

Keyword(s):

Systematic Review ◽

Animal Models ◽

Platelet Rich Plasma ◽

Periodontal Regeneration ◽

In Vitro Studies ◽

In Vivo Studies ◽

Cell Sources ◽

Study Designs

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.

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Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

Alternatives to Laboratory Animals ◽

10.1177/026119299302100209 ◽

1993 ◽

Vol 21 (2) ◽

pp. 173-180

Author(s):

Gunnar Johanson

Keyword(s):

Risk Assessment ◽

Whole Body ◽

External Exposure ◽

Target Dose ◽

Toxic Response ◽

Route Of Exposure ◽

Vitro Data ◽

In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

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MATURATION OF HEMOLYSIN-PRODUCING CELL CLONES

Journal of Experimental Medicine ◽

10.1084/jem.131.6.1261 ◽

1970 ◽

Vol 131 (6) ◽

pp. 1261-1270 ◽

Cited By ~ 4

Author(s):

George C. Saunders ◽

Douglas Swartzendruber

Keyword(s):

Bone Marrow ◽

Doubling Time ◽

Sheep Erythrocyte ◽

Mature Animal ◽

Cell Clones ◽

Initial Appearance ◽

Vitro Data ◽

In Vitro Data

Cells capable of reacting with sheep erythrocyte (SRBC) antigen to maturate and produce hemolysin appear simultaneously in the bone marrow and spleen of 1-day old Swiss-Webster mice. However, hemolysin-producing cell clones (HPCC) do not result. Complete functional precursor units generally appear in the spleens of mice older than 3 days. In vivo and in vitro data correlate well in this regard. Complete precursor units are not seen in the bone marrow and only very rarely in the thymus. The efficiency of precursor units of neonatal mice when they become functional approximates that of the mature animal when based on the doubling time of plaque-forming cells (PFC). Possible explanations of the initial appearance of incomplete precursor units have been discussed.

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Two Drosophila Innexins Are Expressed in Overlapping Domains and Cooperate to Form Gap-Junction Channels

Molecular Biology of the Cell ◽

10.1091/mbc.11.7.2459 ◽

2000 ◽

Vol 11 (7) ◽

pp. 2459-2470 ◽

Cited By ~ 52

Author(s):

Lucy A. Stebbings ◽

Martin G. Todman ◽

Pauline Phelan ◽

Jonathan P. Bacon ◽

Jane A. Davies

Keyword(s):

Gap Junctions ◽

Gap Junction ◽

Ectopic Expression ◽

In Vivo Studies ◽

Electrophysiological Properties ◽

Gap Junction Channels ◽

Overlapping Domains ◽

In Vitro Data

Members of the innexin protein family are structural components of invertebrate gap junctions and are analogous to vertebrate connexins. Here we investigate two Drosophila innexin genes,Dm-inx2 and Dm-inx3 and show that they are expressed in overlapping domains throughout embryogenesis, most notably in epidermal cells bordering each segment. We also explore the gap-junction–forming capabilities of the encoded proteins. In pairedXenopus oocytes, the injection of Dm-inx2mRNA results in the formation of voltage-sensitive channels in only ∼ 40% of cell pairs. In contrast, Dm-Inx3 never forms channels. Crucially, when both mRNAs are coexpressed, functional channels are formed reliably, and the electrophysiological properties of these channels distinguish them from those formed by Dm-Inx2 alone. We relate these in vitro data to in vivo studies. Ectopic expression ofDm-inx2 in vivo has limited effects on the viability ofDrosophila, and animals ectopically expressingDm-inx3 are unaffected. However, ectopic expression of both transcripts together severely reduces viability, presumably because of the formation of inappropriate gap junctions. We conclude that Dm-Inx2 and Dm-Inx3, which are expressed in overlapping domains during embryogenesis, can form oligomeric gap-junction channels.

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Antiproliferative activity of thiazole and oxazole derivatives: A systematic review of in vitro and in vivo studies

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111495 ◽

2021 ◽

Vol 138 ◽

pp. 111495

Author(s):

Nancy Y. Guerrero-Pepinosa ◽

María C. Cardona-Trujillo ◽

Sandra C. Garzón-Castaño ◽

Luz Angela Veloza ◽

Juan C. Sepúlveda-Arias

Keyword(s):

Systematic Review ◽

Antiproliferative Activity ◽

In Vivo Studies ◽

Oxazole Derivatives

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Medicinal Plants with Anti-Trichomonas vaginalis Activity in Iran: A Systematic Review

Iranian Journal of Parasitology ◽

10.18502/ijpa.v14i1.712 ◽

2019 ◽

Cited By ~ 2

Author(s):

Hajar ZIAEI HEZARJARIBI ◽

Najmeh NADEALI ◽

Mahdi FAKHAR ◽

Masoud SOOSARAEI

Keyword(s):

Systematic Review ◽

Medicinal Plants ◽

Trichomonas Vaginalis ◽

Scientific Information ◽

Medicinal Herbs ◽

In Vivo Studies ◽

Eligibility Criteria ◽

Sexually Transmitted

Background: Trichomoniasis, due to Trichomonas vaginalis, is one of the most common sexually transmitted parasitic diseases in the world such as Iran. This systematic review aimed to explore the studies evaluating the medicinal herbs with anti- T. vaginalis activity which used in Iran. Methods: Articles published in 4 Persian and 4 English databases were obtained between 2000 and 2015 including Google Scholar, PubMed, Science Direct, Scopus, Magiran, Barakatkns (formerly IranMedex), Elm net, and SID (Scientific Information Database). Studies out of Iran, studies on animal models and articles on other parasite species than T. vaginalis were excluded from this review. Results: Twenty-one articles including in vitro experiments, met our eligibility criteria. Thoroughly, 26 types of plants were examined against T. vaginalis. Medicinal herbs such as Artemisia, Zataria multiflora, and Lavandula angustifolia are remarkably effective on T. vaginalis. As such, use of other parts of these plants in different concentrations and timelines is recommended for future in vivo studies. Conclusion: The present systematic review provides comprehensive and useful information about Iranian medicinal plants with anti-T. vaginalis activity, which would be examined in the future experimental and clinical trials and herbal combination therapy.

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Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

International Journal of High Dilution Research - ISSN 1982-6206 ◽

10.51910/ijhdr.v14i2.787 ◽

2021 ◽

Vol 14 (2) ◽

pp. 52-52

Author(s):

Aloisio Cunha de Carvalho ◽

Leoni Villano Bonamin

Keyword(s):

Systematic Review ◽

Experimental Studies ◽

Pharmaceutical Preparations ◽

Viscum Album ◽

In Vitro Models ◽

In Vivo Studies ◽

Pubmed Database ◽

Anti Cancer

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

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