Therapeutic Potential of Biofilm-Dispersing Enzymes

2009 ◽  
Vol 32 (9) ◽  
pp. 545-554 ◽  
Author(s):  
Jeffrey B. Kaplan
Keyword(s):  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Film Formation ◽  
In Vivo Studies ◽  
Bacterial Cells ◽  
Deoxyribonuclease I ◽  
Treatment And Prevention ◽  
Biofilm Matrix

Surface-attached colonies of bacteria known as biofilms play a major role in the pathogenesis of medical device infections. Biofilm colonies are notorious for their resistance to antibiotics and host defenses, which makes most device infections difficult or impossible to eradicate. Bacterial cells in a biofilm are held together by an extracellular polymeric matrix that is synthesized by the bacteria themselves. Enzymes that degrade biofilm matrix polymers have been shown to inhibit bio film formation, detach established bio film colonies, and render biofilm cells sensitive to killing by antimicrobial agents. This review discusses the potential use of biofilm matrix-degrading enzymes as anti-biofilm agents for the treatment and prevention of device infections. Two enzymes, deoxyribonuclease I and the glycoside hydrolase dispersin B, will be reviewed in detail. In vitro and in vivo studies demonstrating the anti-biofilm activities of these two enzymes will be summarized, and the therapeutic potential and possible drawbacks of using these enzymes as clinical agents will be discussed.

scholarly journals Chloramphenicol Resurrected: A Journey from Antibiotic Resistance in Eye Infections to Biofilm and Ocular Microbiota

2019 ◽  
Vol 7 (9) ◽  
pp. 278 ◽  
Author(s):  
Lorenzo
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
In Vivo Studies ◽  
Antibiofilm Activity ◽  
Eye Infections ◽  
Treatment And Prevention ◽  
Old Drugs

The advent of multidrug resistance among pathogenic bacteria is devastating the worth of antibiotics and changing the way of their administration, as well as the approach to use new or old drugs. The crisis of antimicrobial resistance is also due to the unavailability of newer drugs, attributable to exigent regulatory requirements and reduced financial inducements. The emerging resistance to antibiotics worldwide has led to renewed interest in old drugs that have fallen into disuse because of toxic side effects. Thus, comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms and optimize the use of old antimicrobial agents able to maintain their profile of susceptibility. Chloramphenicol is experiencing its renaissance because it is widely used in the treatment and prevention of superficial eye infections due to its broad spectrum of activity and other useful antimicrobial peculiarities, such as the antibiofilm properties. Concerns have been raised in the past for the risk of aplastic anemia when chloramphenicol is given intravenously. Chloramphenicol seems suitable to be used as topical eye formulation for the limited rate of resistance compared to fluoroquinolones, for its scarce induction of bacterial resistance and antibiofilm activity, and for the hypothetical low impact on ocular microbiota disturbance. Further in-vitro and in vivo studies on pharmacodynamics properties of ocular formulation of chloramphenicol, as well as its real impact against biofilm and the ocular microbiota, need to be better addressed in the near future.

scholarly journals Antimicrobial Activity from Species Plectranthus amboinicus (Lour.) Spreng, a Review

2020 ◽  
pp. 1-14
Author(s):  
Juliane Maria dos Santos Silva ◽  
Jackson Roberto Guedes da Silva Almeida ◽  
Cristiane dos Santos Cerqueira Alves ◽  
Daniel Amando Nery ◽  
Livia Maria Oliveira Damasceno ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Synergistic Activity ◽  
Popular Medicine ◽  
Plectranthus Amboinicus

Introduction: Nowadays, several bacteria have acquired resistance to available antimicrobial agents making necessary the search for new therapeutic alternatives. Plectranthus amboinicus L. is a succulent and aromatic herb, popularly known as thick leaf mint, used in popular medicine for the treatment of colds, digestive diseases, asthma, headache and to fight pathogenic bacteria activity. In view the antimicrobial activity of P. amboinicus this study had as aim to review publications involving researches about antimicrobial activity of this species. Materials and Methods: For this, PubMed, Scopus, Science Direct and Scielo databases were consulted in November 2020 using the keywords Plectranthus amboinicus and antimicrobial activity. In vitro and/or in vivo studies on the antimicrobial activity of the species in the last 10 years were considered. Results: The main microorganisms evaluated were: Klebsiella pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and some Candida species. The essential oils had carvacrol, germacrene D, thymol and camphor as main constituents. Most studies evaluated the antimicrobial activity using broth dilution and agar diffusion methods. In most studies essential oil, extracts and/or isolated substances showed significant antimicrobial activity. Synergistic activity was also observed through association with antibiotics. Conclusion: P. amboinicus has therapeutic potential for antimicrobial treatments and can be an alternative to the treatment of resistant microorganisms and that further in vivo and clinical studies with the species are still needed.

Medicinal Plants and Bioactive Compounds for Diabetes Management: Important Advances for Drug Discovery

2020 ◽  
Vol 26 ◽  
Author(s):  
Kondeti Ramudu Shanmugam ◽  
Bhasha Shanmugam ◽  
Gangigunta Venkatasubbaiah ◽  
Sahukari Ravi ◽  
Kesireddy Sathyavelu Reddy
Keyword(s):  
Herbal Medicine ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Diabetes Management ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Major Public Health Problem

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

scholarly journals Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1248
Author(s):  
Muhammad Waleed Baig ◽  
Humaira Fatima ◽  
Nosheen Akhtar ◽  
Hidayat Hussain ◽  
Mohammad K. Okla ◽  
...  
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Metabolic Reaction ◽  
Datura Innoxia ◽  
In Vivo Models ◽  
Immobility Time ◽  
Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

scholarly journals Click Activated Protodrugs Against Cancer Increase the Therapeutic Potential of Chemotherapy through Local Capture and Activation

2020 ◽  
Author(s):  
Kui Wu ◽  
Nathan Yee ◽  
Sangeetha Srinivasan ◽  
Amir Mahmoodi ◽  
Michael Zakharian ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Unmet Need ◽  
Sodium Hyaluronate ◽  
Maximum Tolerated Dose ◽  
The Body ◽  
In Vivo Studies ◽  
Tumor Biomarker ◽  
Tumor Site

<div> <div> <div> <p>A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)- modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapy. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. Studies in rodents show that a single injection of the tetrazine-modified biopolymer, SQL70, efficiently captures SQP33 protodrug doses given at 10.8-times the maximum tolerated dose of conventional doxorubicin with greatly reduced systemic toxicity. </p> </div> </div> </div>

scholarly journals Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 188 ◽  
Author(s):  
Filip Vlavcheski ◽  
Mariah Young ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Pathological Condition ◽  
Current Treatment ◽  
In Vivo Studies ◽  
Olive Leaves ◽  
Treatment And Prevention ◽  
Antidiabetic Effects

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

scholarly journals Plant Products as Antimicrobial Agents

1999 ◽  
Vol 12 (4) ◽  
pp. 564-582 ◽  
Author(s):  
Marjorie Murphy Cowan
Keyword(s):  
Secondary Metabolites ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Traditional Healers ◽  
In Vivo Studies ◽  
Current Status ◽  
The Public ◽  
The Earth

SUMMARY The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

scholarly journals Effect of Low-Immunogenic Yogurt Drinks and Probiotic Bacteria on Immunoreactivity of Cow’s Milk Proteins and Tolerance Induction—In Vitro and In Vivo Studies

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3390
Author(s):  
Barbara Wróblewska ◽  
Anna Kaliszewska-Suchodoła ◽  
Ewa Fuc ◽  
Lidia Hanna Markiewicz ◽  
Anna Maria Ogrodowczyk ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Tolerance Induction ◽  
Milk Proteins ◽  
In Vivo Studies ◽  
Cow’S Milk ◽  
Milk Allergy ◽  
Cow's Milk ◽  
Safe Product

There is no effective therapy for milk allergy. The role of lactic acid bacteria (LAB) and probiotics in protection against allergy-related outcomes is still under investigation. The aim of the study was to evaluate the immunomodulative and therapeutic potential of yogurt drinks in cow’s milk allergy (CMA) management. We compared immunoreactivity of α-casein (α-CN), β-casein (β-CN), κ-casein (κ-CN), α-lactalbumin (α-LA), and β-lactoglobulin (β-LG) in 27 yogurt drinks fermented with different basic yogurt cultures, or yogurt cultures enriched with Lactobacillus plantarum and/or Bifidobacterium lactis strains, by competitive ELISA assay. Drinks with the lowest antigenic potential were used as allergoids for CMA therapy. BALB/c mice were sensitized via intraperitoneal injection of α-CN + β-LG mixture with aluminum adjuvant, and gavaged with increasing doses of selected low-immunogenic drinks (YM—basic, or YM-LB—enriched with L. plantarum and B. lactis) to induce tolerance. Milk- or phosphate-buffered saline (PBS)-dosed mice served as controls. Compared to milk, the immunoreactivity of proteins in drinks increased or decreased, depending on the bacterial sets applied for fermentation. Only a few sets acted synergistically in reducing immunoreactivity. The selected low-immunogenic drinks stimulated allergic mice for profiling Th2 to Th1 response and acquire tolerance, and the effect was greater with YM-LB drink, which during long-lasting interventional feeding strongly increased the secretion of regulatory cytokines, i.e., IL-10 and TGF-β, and IgA and decreased IL-4, IgE, and anti-(α-CN + β-LG) IgG1. The studies revealed variations in the potency of yogurt bacteria to change allergenicity of milk proteins and the need for their strict selection to obtain a safe product for allergy sufferers. The YM-LB drink with reduced antigenic potential may be a source of allergoids used in the immunotherapy of IgE mediated CMA, but further clinical or volunteer studies are required.

scholarly journals Safety and Utility of Chloroquine/ Hydroxychloroquine in Palliative Care Patients

2020 ◽  
pp. 104990912095277
Author(s):  
Eric Prommer
Keyword(s):  
Palliative Care ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Symptom Control ◽  
In Vivo Studies ◽  
Advanced Illness ◽  
Know How ◽  
Seriously Ill

The coronavirus disease 2019 (COVID-19) pandemic represents a significant healthcare challenge for the world. Many drugs have therapeutic potential. The aminoquinolones, hydroxychloroquine, and chloroquine are undergoing evaluation as a potential therapy against COVID -19. In vitro and in vivo studies suggest that these drugs affect viral adherence and modify inflammatory responses, which may provide some impact on the symptoms associated with COVID. As palliative care specialists encounter more COVID positive patients, palliative care specialists need to know how these drugs work, and importantly how they interact with palliative care drugs used for symptom control. At the same time, there is a need to reduce polypharmacy in any seriously ill patient population. The goals of this paper are to identify whether or not hydroxychloroquine/chloroquine improves symptoms in palliative care patients and whether or not these drugs are safe to use in the advanced illness population who have COVID.

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