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Current Opinion in HIV and AIDS Jul 2013Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3... (Review)
Review
PURPOSE OF REVIEW
Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates.
RECENT FINDINGS
Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials.
SUMMARY
Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.
Topics: Animals; Anti-Infective Agents, Local; Anti-Retroviral Agents; Disease Models, Animal; Disease Transmission, Infectious; Drug Evaluation, Preclinical; Female; HIV Infections; Humans; Macaca mulatta; Research Design; Simian Acquired Immunodeficiency Syndrome
PubMed: 23698560
DOI: 10.1097/COH.0b013e328361d096 -
International Journal of Molecular... Sep 2021The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a... (Review)
Review
The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.
Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Antiparasitic Agents; Antiviral Agents; Blood Platelets; Humans; Ribonucleases
PubMed: 34638568
DOI: 10.3390/ijms221910230 -
Annual Review of Medicine Jan 2020HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum... (Review)
Review
HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum have the potential to prevent the sexual acquisition of HIV in women and men. Topical microbicides may meet the prevention needs of individuals and groups for whom oral daily forms of pre-exposure prophylaxis (PrEP) have not been acceptable. Microbicides can provide personal control over HIV prevention and offer the possibility of discreet use, qualities that may be particularly important for receptive partners in sexual relationships such as women and transgender women and men, who together account for the clear majority of new HIV infections worldwide. Although the promise of such a product emerged nearly three decades ago, proof of concept has been demonstrated only within the last decade. A robust pipeline of microbicidal gels, films, inserts, and rings has been evaluated in multiple studies among at-risk women and men, and refinement of products for ease of use, reversibility, and high safety is the priority for the field.
Topics: Adult; Anti-HIV Agents; Anti-Infective Agents, Local; Drug Compounding; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Male; Patient Safety; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Rectum; Sexual Partners; Vagina
PubMed: 31613684
DOI: 10.1146/annurev-med-090518-093731 -
Journal of Applied Microbiology Nov 2017Silver has attracted a lot of attention as a powerful, broad spectrum and natural antimicrobial agent since the ancient times because of its nontoxic nature to the human... (Review)
Review
Silver has attracted a lot of attention as a powerful, broad spectrum and natural antimicrobial agent since the ancient times because of its nontoxic nature to the human body at low concentrations. It has been used in treatment of various infections and ulcers, storage of water and prevention of bacterial growth on the surfaces and within materials. However, there are numerous medical and health benefits of colloidal or nanosilver apart from its microbicidal ability which as yet has not been fully embraced by the medical community. These include antiplatelet activity, antioxidant effect, anticancer activity, wound healing and bone regeneration, enhancement of immunity, and increase in antibiotic efficiency. Additionally silver also provides protection against alcohol toxicity, upper respiratory tract infections and stomach ailments. Although nanosilver has been proposed for various topical applications, its usage by ingestion and inhalation remains controversial due to the lack of detailed and precise toxicity information. These beneficial properties of silver can be utilized by using silver at very low concentrations which are not harmful to the human body and environment. The following review discusses the diverse medical applications of silver and further recommends human clinical studies for its in vivo usage.
Topics: Animals; Anti-Infective Agents; Dose-Response Relationship, Drug; Humans; Silver
PubMed: 28650591
DOI: 10.1111/jam.13525 -
Best Practice & Research. Clinical... Aug 2012The development of safe topical microbicides that effectively prevent human immunodeficiency virus (HIV) infection is a major goal in curbing the human immunodeficiency... (Review)
Review
The development of safe topical microbicides that effectively prevent human immunodeficiency virus (HIV) infection is a major goal in curbing the human immunodeficiency virus pandemic. A number of past failures resulting from mucosal toxicity or lack of efficacy have informed the field. Products that caused toxicity to the female genital tract mucosa, and thereby increased the likelihood of HIV acquisition, included nonoxynol 9, cellulose sulfate, and C31 G vaginal gel Savvy. Topical products that were ineffective in preventing HIV infection include BufferGel, Carraguard, and PRO 2000. Antiretroviral drugs such as tenofovir and dapivirine formulated into microbicide products have shown promise, but there is much to learn about ideal product formulation and acceptability, and drug distribution and disposition (pharmacokinetics). Current formulations for water-soluble molecules include vaginally or rectally applied gels, vaginal rings, films and tablets. Dosing strategies (e.g. coitally dependent or independent) will be based on the pharmacokinetics of the active ingredient and the tolerance for less than perfect adherence.
Topics: Adenine; Animals; Anti-HIV Agents; Anti-Infective Agents, Local; Female; HIV; HIV Infections; Humans; Mice; Organophosphonates; Tenofovir; Treatment Outcome; Vaginal Creams, Foams, and Jellies
PubMed: 22306523
DOI: 10.1016/j.bpobgyn.2012.01.004 -
Current HIV Research Jan 2012There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the... (Review)
Review
There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.
Topics: Administration, Topical; Animals; Anti-Infective Agents, Local; Anti-Retroviral Agents; Disease Models, Animal; Drug Evaluation, Preclinical; HIV Infections; HIV-1; Macaca mulatta; Mice; Rabbits; Rats
PubMed: 22264049
DOI: 10.2174/157016212799304715 -
Lancet (London, England) Mar 200725 years after the first HIV/AIDS cases emerged in 1981, the disease continues to spread worldwide, with about 15 000 new infections every day. Although highly active... (Review)
Review
25 years after the first HIV/AIDS cases emerged in 1981, the disease continues to spread worldwide, with about 15 000 new infections every day. Although highly active antiretroviral therapy (HAART) has greatly reduced the rate of HIV infection, and the spread of the epidemic, this effect has largely been seen in developed countries. More than 90% of HIV-infected people live in developing countries, most of whom do not have access to this treatment. The development of efficient, widely available, and low-cost microbicides (gels and creams can be applied topically before sex) to prevent sexually transmitted HIV infections should be given high priority. We review different categories of microbicide drugs and lead compounds, their mechanism of action, current status of development, and progress in phase III trials.
Topics: Anti-HIV Agents; Anti-Infective Agents, Local; Buffers; Clinical Trials, Phase III as Topic; Detergents; Disease Transmission, Infectious; Drug Evaluation, Preclinical; Female; HIV; HIV Infections; Humans; Male; Models, Theoretical; Surface-Active Agents; Treatment Outcome; Virus Internalization
PubMed: 17336656
DOI: 10.1016/S0140-6736(07)60202-5 -
Critical Reviews in Microbiology Feb 2021Biofilms are complex microbial architectures that encase microbial cells in a matrix comprising self-produced extracellular polymeric substances. Microorganisms living... (Review)
Review
Biofilms are complex microbial architectures that encase microbial cells in a matrix comprising self-produced extracellular polymeric substances. Microorganisms living in biofilms are much more resistant to hostile environments than their planktonic counterparts and exhibit enhanced resistance against the microbicides. From the human perspective, biofilms can be classified into beneficial, neutral, and harmful. Harmful biofilms impact food safety, cause plant and animal diseases, and threaten medical fields, making it urgent to develop effective and robust strategies to control harmful biofilms. In this review, we discuss various strategies to control biofilm formation on infected tissues, implants, and medical devices. We classify the current strategies into three main categories: (i) changing the properties of susceptible surfaces to prevent biofilm formation; (ii) regulating signalling pathways to inhibit biofilm formation; (iii) applying external forces to eradicate the biofilm. We hope this review would motivate the development of innovative and effective strategies for controlling harmful biofilms.
Topics: Animals; Anti-Infective Agents; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Biofilms; Humans; Prostheses and Implants
PubMed: 33356690
DOI: 10.1080/1040841X.2020.1842325 -
International Journal of Molecular... May 2013Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers... (Review)
Review
Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.
Topics: Animals; Anti-Infective Agents; Bacteria; Bacterial Infections; Cations; Fungi; Humans; Lipids; Microbial Sensitivity Tests; Mycoses; Polymers; Surface-Active Agents
PubMed: 23665898
DOI: 10.3390/ijms14059906 -
Molecules (Basel, Switzerland) Jan 2023The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of... (Review)
Review
The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of synthetic and semi-synthetic antimicrobial drugs, the spread of drug-resistant clinical isolates has increased, and research is directed towards natural products, such as essential oils, as useful antimicrobial resources. In the context of a prospective infection, we compared the impact of essential oils and common antimicrobial agents on the microbicidal activity of human phagocytes. Here, we present the results of our decades-long investigation into the effectiveness of thyme red oil (26.52% thymol chemotype), tea tree oil (TTO), and Mentha of Pancalieri [( (Huds) var. (Sole), form (Camus) ()] essential oils on human polymorphonuclear leukocytes (PMNs) capacity to kill clinical strains of and when compared to three antifungal drugs used to treat candidiasis (fluconazole, anidulafungin, and caspofungin) These essential oils demonstrate antifungal drug-like and/or superior efficacy in enhancing intracellular killing by PMNs, even at subinhibitory concentrations. Our results are compared with data in the literature on essential oils and immune system interactions. This comparison would aid in identifying therapeutic solutions to the increasingly prevalent antibiotic resistance as well as filling in any remaining knowledge gaps on the bioactivity of essential oils.
Topics: Humans; Oils, Volatile; Antifungal Agents; Prospective Studies; Fluconazole; Plant Oils; Anti-Infective Agents; Microbial Sensitivity Tests
PubMed: 36615625
DOI: 10.3390/molecules28010435