scholarly journals Pharmacodynamics of non-replicating viruses, bacteriocins and lysins

2006 ◽  
Vol 273 (1602) ◽  
pp. 2703-2712 ◽  
Author(s):  
James J Bull ◽  
Roland R Regoes
Keyword(s):  
Mathematical Models ◽  
Cancer Treatment ◽  
Single Molecule ◽  
Bacterial Infections ◽  
Therapeutic Agent ◽  
Phage Therapy ◽  
Therapeutic Agents ◽  
Chemotherapeutic Agents ◽  
Adsorption Rates ◽  
The Impact

The pharmacodynamics of antibiotics and many other chemotherapeutic agents is often governed by a ‘multi-hit’ kinetics, which requires the binding of several molecules of the therapeutic agent for the killing of their targets. In contrast, the pharmacodynamics of novel alternative therapeutic agents, such as phages and bacteriocins against bacterial infections or viruses engineered to target tumour cells, is governed by a ‘single-hit’ kinetics according to which the agent will kill once it is bound to its target. In addition to requiring only a single molecule for killing, these agents bind irreversibly to their targets. Here, we explore the pharmacodynamics of such ‘irreversible, single-hit inhibitors’ using mathematical models. We focus on agents that do not replicate, i.e. in the case of phage therapy, we deal only with non-lytic phages and in the case of cancer treatment, we restrict our analysis to replication of incompetent viruses. We study the impact of adsorption on dead cells, heterogeneity in adsorption rates and spatial compartmentalization.

scholarly journals The Effect of Antimicrobial Drugs Tylocolinum, Tetragold and Cidisept-o on Escherichia coli Ultrastructure

2013 ◽  
Vol 2 (3) ◽  
pp. 65
Author(s):  
A. G. Shakhov ◽  
D. V. Fedosov ◽  
L. Y. Sashnina ◽  
O. V. Kazimirov
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Water Solution ◽  
Uranyl Acetate ◽  
Chemotherapeutic Agents ◽  
Control Culture ◽  
New Drugs ◽  
Ultrastructural Changes ◽  
The Impact

<p>As a result of wide antibiotics, sulfonamides and other antimicrobial agents usage for the therapy of the animals with the bacterial infections caused by various causative agents including <em>Escherichia coli</em>, many microorganisms gained resistance to the chemotherapeutic agents. New combined drugs are being worked out during recent years, the components of which have various influence mechanisms on the bacterial cell that helps to provide resistance forming control. The results of the researches of the new antimicrobial agents, containing antibiotics in their composition, and non-antibiotic agent influence on the ultrastructure of <em>Escherichia coli</em> are represented in this study.</p> <p>5-hour <em>Escherichia coli 866</em> culture was processed by the drugs of the minimum bactericidal (Tylocolinum-0.39 µg/ml, Tetragold-6.25 µg/ml, Cidisept-o-25 µg/ml) and 4-time concentrations during 3 hours. Samples and control culture (without drugs) were fixed by the 2.5% glutaricdialdehyde on the s-Collidine Buffer, dehydrated in the ethanol with rising concentration, filled in epoxies. Ultrathin slices were stained by 2% water solution of uranyl acetate and lead citrate for 10 minutes. Then they were examined with the use of the electron microscope JEM-100 CX II by JEOL.</p> <p>The research showed deep ultrastructural changes in <em>Escherichia coli</em> cells under the antimicrobial agent influence determined by synergistic effect of combined Tylocolinum and Tetragold drugs components, possessing various bacteria influencing mechanisms, and aldehyde that is a component of Cidisept-o.</p> The electron microscopy usage allows to get unique information about the impact consequences of the traditional improved drugs and new drugs with antimicrobial activity on the bacterial infectious agents.

scholarly journals Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs’ Dosage Ratio Effect

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1035 ◽  
Author(s):  
Jiayi Pan ◽  
Kobra Rostamizadeh ◽  
Nina Filipczak ◽  
Vladimir Torchilin
Keyword(s):  
Cancer Therapy ◽  
Cancer Treatment ◽  
Therapeutic Agent ◽  
Polymeric Nanoparticles ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Individual Therapy ◽  
Multiple Factors ◽  
Therapeutic Outcomes ◽  
Anti Cancer

Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy. Ideally, combination therapy inhibits tumor growth through multiple pathways by enhancing the performance of each individual therapy, often resulting in a synergistic effect. Polymeric nanoparticles prepared from block co-polymers have been a popular platform for co-delivery of combinations of drugs associated with the multiple functional compartments within such nanoparticles. Various polymeric nanoparticles have been applied to achieve enhanced therapeutic efficacy in cancer therapy. However, reported drug ratios used in such systems often vary widely. Thus, the same combination of drugs may result in very different therapeutic outcomes. In this review, we investigated polymeric co-delivery systems used in cancer treatment and the drug combinations used in these systems for synergistic anti-cancer effect. Development of polymeric co-delivery systems for a maximized therapeutic effect requires a deeper understanding of the optimal ratio among therapeutic agents and the natural heterogenicity of tumors.

scholarly journals A recent development of new therapeutic agents and novel drug targets for cancer treatment

2021 ◽  
Vol 9 ◽  
pp. 205031212110670
Author(s):  
Zemene Demelash Kifle ◽  
Meklit Tadele ◽  
Eyerusalem Alemu ◽  
Tadele Gedamu ◽  
Akeberegn Gorems Ayele
Keyword(s):  
Drug Resistance ◽  
Cancer Treatment ◽  
Drug Targets ◽  
Therapeutic Agents ◽  
Chemotherapeutic Agents ◽  
Cross Resistance ◽  
Drug Induced ◽  
Induced Apoptosis ◽  
Novel Drug ◽  
Novel Drug Targets

Despite recent advances in cancer diagnosis, prevention, detection, as well as management, the disease is expected to be the top cause of death globally. The chemotherapy approach for cancer has become more advanced in its design, yet no medication can cure enough against all types of cancer and its stage. Thus, this review aimed to summarize a recent development of new therapeutic agents and novel drug targets for the treatment of cancer. Several obstacles stand in the way of effective cancer treatment and drug development, including inaccessibility of tumor site by appropriate drug concentration, debilitating untoward effects caused by non-selective tissue distribution of chemotherapeutic agents, and occurrence of drug resistance, which leads to cross-resistance to a variety of drugs. Resistance to treatment with anticancer drugs results from multiple factors and the most common reason for acquiring drug resistance is marking and expelling drugs that prevent cancer cells to be targeted by chemotherapeutic agents. Moreover, insensitivity to drug-induced apoptosis, alteration, and mutation of drug target and interference/change of DNA replication are other main causes of treatment failure.

scholarly journals A Localized Phage-Based Antimicrobial System: Effect of Alginate on Phage Desorption from β-TCP Ceramic Bone Substitutes

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 560
Author(s):  
Rached Ismail ◽  
Natalia D. Dorighello Carareto ◽  
Jean-Christophe Hornez ◽  
Franck Bouchart
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Local Treatment ◽  
Bone Substitutes ◽  
Prosthetic Material ◽  
System Effect ◽  
Promising Alternative ◽  
Alternative Approaches ◽  
Resistant Strains ◽  
The Impact

Tricalcium phosphate (TCP) is a prosthetic material commonly used as a bone substitute to repair osteoarticular diseases and injuries. In this type of bone reconstruction surgery, antibiotics remain the common preventive and therapeutic treatment for bacterial infection. Nevertheless, the emergence of multi-resistant strains requires complimentary or alternative treatments. Today, one of the promising alternative approaches is phage therapy. Phages are bacterial viruses that have several advantages over chemotherapy, such as the specificity of bacterial strain, the absence of side effects, and a rapid response. In this work, we studied the impact of alginate hydrogels for overlaying λvir-phage-loaded β-TCP ceramic bone substitutes, delaying the phage desorption. The results show that the use of a 1% alginate–CaCl2 hydrogel overlapping the β-TCP ceramic pellets leads to higher initial phage concentration on the material and extends the released time of phages to two weeks when compared with control pellets. These alginate-coated biomaterials also generate faster bacterial lysis kinetics and could therefore be a good practical prosthetic device for bone and joint surgeries by allowing local treatment of bacterial infections with phage therapy for a longer period of time.

scholarly journals Nanomaterial Complexes Enriched With Natural Compounds Used in Cancer Therapies: A Perspective for Clinical Application

2021 ◽  
Vol 11 ◽  
Author(s):  
María Zenaida Saavedra-Leos ◽  
Euclides Jordan-Alejandre ◽  
César López-Camarillo ◽  
Amaury Pozos-Guillen ◽  
César Leyva-Porras ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Bacterial Infections ◽  
Positive Response ◽  
Natural Compounds ◽  
Molecular Characteristics ◽  
Cancer Therapies ◽  
Cancer Types ◽  
The Impact

Resveratrol and quercetin are natural compounds contained in many foods and beverages. Reports indicate implications for the health of the general population; on the other hand the use of both compounds has interesting results for the treatment of many diseases as cardiovascular affections, diabetes, Alzheimer’s disease, viral and bacterial infections among others. Based on their capacities described as anti-inflammatory, antioxidant, and anti-aging, resveratrol and quercetin showed antiproliferative and anticancer activity specifically in maligned cells. These molecular characteristics trigger the pharmacological repurposing of both compounds and improved its research for treating different cancer types with interesting results at in vitro, in vivo, and clinical trial studies. Meanwhile, the development of different systems of drug release in specific sites as nanomaterials and specifically the nanoparticles, potentiates the personal treatment perspective in conjunct with the actual cancer therapies; regularly invasive and aggressive, the perspective of nanomedicine as higher effective and lower invasive has gained popularity. Knowledge of molecular interactions of resveratrol and quercetin in diseases confirms the evidence of multiple benefits, while the multiple analyses suggested a positive response for the treatment and diagnostics of cancer in different stages, including at metastatic stage. The present work reviews the reports related to the impact of resveratrol and quercetin in cancer treatment and its effects when the antioxidants are encapsulated in different nanoparticle systems, which improve the prospects of cancer treatment.

scholarly journals Phage Therapy of Pneumonia Is Not Associated with an Overstimulation of the Inflammatory Response Compared to Antibiotic Treatment in Mice

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Nicolas Dufour ◽  
Raphaëlle Delattre ◽  
Anne Chevallereau ◽  
Jean-Damien Ricard ◽  
Laurent Debarbieux
Keyword(s):  
Inflammatory Response ◽  
Antibiotic Treatment ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Bacterial Load ◽  
The United States ◽  
Experimental Models ◽  
Interleukin 12 ◽  
The Impact

ABSTRACT Supported by years of clinical use in some countries and more recently by literature on experimental models, as well as its compassionate use in Europe and in the United States, bacteriophage (phage) therapy is providing a solution for difficult-to-treat bacterial infections. However, studies of the impact of such treatments on the host remain scarce. Murine acute pneumonia initiated by intranasal instillation of two pathogenic strains of Escherichia coli (536 and LM33) was treated by two specific bacteriophages (536_P1 and LM33_P1; intranasal) or antibiotics (ceftriaxone, cefoxitin, or imipenem-cilastatin; intraperitoneal). Healthy mice also received phages alone. The severity of pulmonary edema, acute inflammatory cytokine concentration (blood and lung homogenates), complete blood counts, and bacterial and bacteriophage counts were determined at early (≤12 h) and late (≥20 h) time points. The efficacy of bacteriophage to decrease bacterial load was faster than with antibiotics, but the two displayed similar endpoints. Bacteriophage treatment was not associated with overinflammation but in contrast tended to lower inflammation and provided a faster correction of blood cell count abnormalities than did antibiotics. In the absence of bacterial infection, bacteriophage 536_P1 promoted a weak increase in the production of antiviral cytokines (gamma interferon [IFN-γ] and interleukin-12 [IL-12]) and chemokines in the lungs but not in the blood. However, such variations were no longer observed when bacteriophage 536_P1 was administered to treat infected animals. The rapid lysis of bacteria by bacteriophages in vivo does not increase the innate inflammatory response compared to that with antibiotic treatment.

scholarly journals Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages

2021 ◽  
Vol 14 (11) ◽  
pp. 1162
Author(s):  
Katarzyna M. Danis-Wlodarczyk ◽  
Alice Cai ◽  
Anna Chen ◽  
Marissa R. Gittrich ◽  
Matthew B. Sullivan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Rapid Determination ◽  
Treatment Success ◽  
Phage Infection ◽  
Virion Production ◽  
Metabolic Activities ◽  
Therapy Studies ◽  
The Impact

Phage therapy is a century-old technique employing viruses (phages) to treat bacterial infections, and in the clinic it is often used in combination with antibiotics. Antibiotics, however, interfere with critical bacterial metabolic activities that can be required by phages. Explicit testing of antibiotic antagonism of phage infection activities, though, is not a common feature of phage therapy studies. Here we use optical density-based ‘lysis-profile’ assays to assess the impact of two antibiotics, colistin and ciprofloxacin, on the bactericidal, bacteriolytic, and new-virion-production activities of three Pseudomonas aeruginosa phages. Though phages and antibiotics in combination are more potent in killing P. aeruginosa than either acting alone, colistin nevertheless substantially interferes with phage bacteriolytic and virion-production activities even at its minimum inhibitory concentration (1× MIC). Ciprofloxacin, by contrast, has little anti-phage impact at 1× or 3× MIC. We corroborate these results with more traditional measures, particularly colony-forming units, plaque-forming units, and one-step growth experiments. Our results suggest that ciprofloxacin could be useful as a concurrent phage therapy co-treatment especially when phage replication is required for treatment success. Lysis-profile assays also appear to be useful, fast, and high-throughput means of assessing antibiotic antagonism of phage infection activities.

scholarly journals Investigating the impact of combination phage and antibiotic therapy: a modeling study

2020 ◽  
Author(s):  
Selenne Banuelos ◽  
Hayriye Gulbudak ◽  
Mary Ann Horn ◽  
Qimin Huang ◽  
Aadrita Nandi ◽  
...  
Keyword(s):  
Immune System ◽  
Combination Therapy ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Antibiotic Use ◽  
Host Immune System ◽  
Drug Classes ◽  
The Impact ◽  
Antibiotic Combination

AbstractAntimicrobial resistance (AMR) is a serious threat to global health today. The spread of AMR, along with the lack of new drug classes in the antibiotic pipeline, has resulted in a renewed interest in phage therapy, which is the use of bacteriophages to treat pathogenic bacterial infections. This therapy, which was successfully used to treat a variety of infections in the early twentieth century, had been largely dismissed due to the discovery of easy to use antibiotics. However, the continuing emergence of antibiotic resistance has motivated new interest in the use of phage therapy to treat bacterial infections. Though various models have been developed to address the AMR-related issues, there are very few studies that consider the effect of phage-antibiotic combination therapy. Moreover, some of biological details such as the effect of the immune system on phage have been neglected. To address these limitations, we utilized a mathematical model to examine the role of the immune response in concert with phage-antibiotic combination therapy compounded with the effects of the immune system on the phages being used for treatment. We explore the effect of phage-antibiotic combination therapy by adjusting the phage and antibiotics dose or altering the timing. The model results show that it is important to consider the host immune system in the model and that frequency and dose of treatment are important considerations for the effectiveness of treatment. Our study can lead to development of optimal antibiotic use and further reduce the health risks of the human-animal-plant-ecosystem interface caused by AMR.

scholarly journals The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

2022 ◽  
Vol 23 (1) ◽  
pp. 488
Author(s):  
Aneta Sevcikova ◽  
Nikola Izoldova ◽  
Viola Stevurkova ◽  
Barbora Kasperova ◽  
Michal Chovanec ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Human Cancer ◽  
Critical Role ◽  
Immune Surveillance ◽  
Treatment Resistance ◽  
Chemotherapeutic Agents ◽  
Limiting Factor ◽  
The Impact

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.

Mechanically-Tunable Quantum Interference in Ferrocene-Based Single-Molecule Junctions

2020 ◽  
Author(s):  
María Camarasa-Gómez ◽  
Daniel Hernangómez-Pérez ◽  
Michael S. Inkpen ◽  
Giacomo Lovat ◽  
E-Dean Fung ◽  
...  
Keyword(s):  
Single Molecule ◽  
Quantum Interference ◽  
Degrees Of Freedom ◽  
Building Blocks ◽  
Ferrocene Derivative ◽  
Single Molecule Junctions ◽  
Molecule Junction ◽  
Single Molecule Junction ◽  
The Impact ◽  
D Orbitals

Ferrocenes are ubiquitous organometallic building blocks that comprise a Fe atom sandwiched between two cyclopentadienyl (Cp) rings that rotate freely at room temperature. Of widespread interest in fundamental studies and real-world applications, they have also attracted<br>some interest as functional elements of molecular-scale devices. Here we investigate the impact of<br>the configurational degrees of freedom of a ferrocene derivative on its single-molecule junction<br>conductance. Measurements indicate that the conductance of the ferrocene derivative, which is<br>suppressed by two orders of magnitude as compared to a fully conjugated analog, can be modulated<br>by altering the junction configuration. Ab initio transport calculations show that the low conductance is a consequence of destructive quantum interference effects that arise from the hybridization of metal-based d-orbitals and the ligand-based π-system. By rotating the Cp rings, the hybridization, and thus the quantum interference, can be mechanically controlled, resulting in a conductance modulation that is seen experimentally.<br>

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