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Best Practice & Research. Clinical... Sep 2019It is expected that the number of surgical procedures to diagnose, treat, and palliate cancers will increase in the near future. While many of those interventions can be... (Review)
Review
It is expected that the number of surgical procedures to diagnose, treat, and palliate cancers will increase in the near future. While many of those interventions can be performed with minimally invasive techniques, others require surgical large incisions and in some instances, they involve multiple areas of the body (i.e., tumor resections with flap reconstructions). Pain after major oncological procedures can be severe and many times difficult to treat as patients can present to the operating room with several conditions including preoperative pain (i.e., rapidly growing tumors and painful neuropathies), opioid tolerance, and contraindications to nonopioid analgesics or regional anesthesia. Inadequately treated postoperative pain is associated with activation of the sympathetic system, postoperative complications, large perioperative opioid use, and an increased risk of developing postoperative persistent pain. Furthermore, it has been theorized that poorly treated pain is associated with cancer recurrence and a reduced survival. Lastly, recent research questions the oncological safety of robotic surgery in gynecological procedures and indicates the need of open surgeries, which will be associated with an increased risk in moderate-to-severe postoperative pain. In conclusion, the management of acute postoperative pain in patients with cancer can be challenging.
Topics: Acute Pain; Drug Tolerance; Humans; Neoplasms; Pain Management; Pain, Postoperative
PubMed: 31785721
DOI: 10.1016/j.bpa.2019.07.018 -
Biochimie May 2024In the ongoing battle against antimicrobial resistance, phenotypic drug tolerance poses a formidable challenge. This adaptive ability of microorganisms to withstand drug... (Review)
Review
In the ongoing battle against antimicrobial resistance, phenotypic drug tolerance poses a formidable challenge. This adaptive ability of microorganisms to withstand drug pressure without genetic alterations further complicating global healthcare challenges. Microbial populations employ an array of persistence mechanisms, including dormancy, biofilm formation, adaptation to intracellular environments, and the adoption of L-forms, to develop drug tolerance. Moreover, molecular mechanisms like toxin-antitoxin modules, oxidative stress responses, energy metabolism, and (p)ppGpp signaling contribute to this phenomenon. Understanding these persistence mechanisms is crucial for predicting drug efficacy, developing strategies for chronic bacterial infections, and exploring innovative therapies for refractory infections. In this comprehensive review, we dissect the intricacies of drug tolerance and persister formation, explore their role in acquired drug resistance, and highlight emerging therapeutic approaches to combat phenotypic drug tolerance. Furthermore, we outline the future landscape of interventions for persistent bacterial infections.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Tolerance; Drug Resistance, Bacterial; Oxidative Stress; Biofilms; Phenotype
PubMed: 38168626
DOI: 10.1016/j.biochi.2023.12.009 -
Drug Delivery and Translational Research Jun 2024Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding... (Review)
Review
Antimicrobial resistance and tolerance (AMR&T) are urgent global health concerns, with alarmingly increasing numbers of antimicrobial drugs failing and a corresponding rise in related deaths. Several reasons for this situation can be cited, such as the misuse of traditional antibiotics, the massive use of sanitizing measures, and the overuse of antibiotics in agriculture, fisheries, and cattle. AMR&T management requires a multifaceted approach involving various strategies at different levels, such as increasing the patient's awareness of the situation and measures to reduce new resistances, reduction of current misuse or abuse, and improvement of selectivity of treatments. Also, the identification of new antibiotics, including small molecules and more complex approaches, is a key factor. Among these, novel DNA- or RNA-based approaches, the use of phages, or CRISPR technologies are some potent strategies under development. In this perspective article, emerging and experienced leaders in drug delivery discuss the most important biological barriers for drugs to reach infectious bacteria (bacterial bioavailability). They explore how overcoming these barriers is crucial for producing the desired effects and discuss the ways in which drug delivery systems can facilitate this process.
Topics: Humans; Anti-Bacterial Agents; Drug Delivery Systems; Animals; Drug Resistance, Microbial; Drug Resistance, Bacterial; Bacteria; Drug Tolerance
PubMed: 38341386
DOI: 10.1007/s13346-023-01513-6 -
Purinergic Signalling Jun 2023Cancer pain is the most prevalent symptom experienced by cancer patients. It substantially impacts a patient's long-term physical and emotional health, making it a... (Review)
Review
Cancer pain is the most prevalent symptom experienced by cancer patients. It substantially impacts a patient's long-term physical and emotional health, making it a pressing issue that must be addressed. Purinergic receptor P2X7 (P2X7R) is a widely distributed and potent non-selective ATP-gated ion channel that regulates tumor proliferation, chronic pain, and the formation of inflammatory lesions in the central nervous system. P2X7R plays an essential role in cancer pain and complications related to cancer pain including depression and opioid tolerance. This review focuses on the structure and distribution of P2X7R, its role in diverse tissues in cancer pain, and the application of P2X7R antagonists in the treatment of cancer pain to propose new ideas for cancer pain management.
Topics: Humans; Cancer Pain; Receptors, Purinergic P2X7; Analgesics, Opioid; Purinergic P2X Receptor Antagonists; Drug Tolerance; Neoplasms
PubMed: 36400869
DOI: 10.1007/s11302-022-09902-1 -
Pain Physician 2015Blood testing is quickly becoming a useful laboratory tool for opioid prescribers who wish to document and assess patient tolerance, more objectively monitor patient... (Review)
Review
Blood testing is quickly becoming a useful laboratory tool for opioid prescribers who wish to document and assess patient tolerance, more objectively monitor patient safety, and evaluate patient compliance using information that is not available with traditional urine drug testing (UDT). Blood testing does not need to be performed as frequently as UDT but provides extremely valuable information which can be used to more accurately evaluate patient compliance and assist with interpreting blood toxicology results commonly used in impairment or overdose cases. This narrative review presents the current evidence supporting the use of blood testing within the chronic pain management setting. In addition, this review aims to introduce and discuss the role of routine blood testing within the chronic pain management setting. Blood testing for the purpose of documenting opioid tolerance is a relatively novel tool for pain physicians and as such this review is not intended to be a comprehensive or exhaustive review of the scientific or medical literature. Prescribers must also be aware that this type of laboratory testing need only be administered to chronic pain patients receiving daily opioid therapy. Patients taking infrequent, low dose, or as needed medications are not anticipated to benefit from this type of test. Based on the complexity of both achieving acceptable outcomes with opioid treatment and the legal and societal issues at hand, we feel that the addition of blood concentration levels will become the standard of care in the near future.
Topics: Analgesics, Opioid; Chronic Pain; Drug Overdose; Drug Tolerance; Health Services Needs and Demand; Hematologic Tests; Humans; Pain Management; Patient Compliance; Substance Abuse Detection
PubMed: 25794214
DOI: No ID Found -
World Journal of Microbiology &... Aug 2018The mechanisms of heavy metal resistance in microbial cells involve multiple pathways. They include the formation of complexes with specific proteins and other... (Review)
Review
The mechanisms of heavy metal resistance in microbial cells involve multiple pathways. They include the formation of complexes with specific proteins and other compounds, the excretion from the cells via plasma membrane transporters in case of procaryotes, and the compartmentalization of toxic ions in vacuoles, cell wall and other organelles in case of eukaryotes. The relationship between heavy metal tolerance and inorganic polyphosphate metabolism was demonstrated both in prokaryotic and eukaryotic microorganisms. Polyphosphates, being polyanions, are involved in detoxification of heavy metals through complex formation and compartmentalization. The bacteria and fungi cultivated in the presence of some heavy metal cations contain the enhanced levels of polyphosphate. In bacteria, polyphosphate sequesters heavy metals; some of metal cations stimulate an exopolyphosphatase activity, which releases phosphate from polyphosphates, and MeHPO ions are then transported out of the cells. In fungi, the overcoming of heavy metal stresses is associated with the accumulation of polyphosphates in cytoplasmic inclusions, vacuoles and cell wall and the formation of cation/polyphosphate complexes. The effects of knockout mutations and overexpression of the genes encoding polyphosphate-metabolizing enzymes on heavy metal resistance are discussed.
Topics: Acid Anhydride Hydrolases; Archaea; Bacteria; Biological Transport; Cations; Cell Membrane; Cell Wall; Drug Tolerance; Eukaryotic Cells; Fungi; Inactivation, Metabolic; Metals, Heavy; Organelles; Phosphates; Phosphotransferases (Phosphate Group Acceptor); Polyphosphates; Prokaryotic Cells
PubMed: 30151754
DOI: 10.1007/s11274-018-2523-7 -
Critical Care Nursing Clinics of North... Jun 2016Prolonged use of sedative medications continues to be a concern for critical care practitioners, with potential adverse effects including tolerance and withdrawal. The... (Review)
Review
Prolonged use of sedative medications continues to be a concern for critical care practitioners, with potential adverse effects including tolerance and withdrawal. The amount of sedatives required in critically ill patients can be lessened and tolerance delayed with the use of pain and/or sedation scales to reach the desired effect. The current recommendation for prolonged sedation is to wean patients from the medications over several days to reduce the risk of drug withdrawal. It is important to identify patients at risk for iatrogenic withdrawal and create a treatment strategy.
Topics: Critical Care Nursing; Critical Illness; Drug Monitoring; Drug Tolerance; Humans; Hypnotics and Sedatives; Intensive Care Units; Substance Withdrawal Syndrome
PubMed: 27215354
DOI: 10.1016/j.cnc.2016.02.010 -
Frontiers in Cellular and Infection... 2022Combination therapy is necessary to treat tuberculosis to decrease the rate of disease relapse and prevent the acquisition of drug resistance, and shorter regimens are... (Review)
Review
Combination therapy is necessary to treat tuberculosis to decrease the rate of disease relapse and prevent the acquisition of drug resistance, and shorter regimens are urgently needed. The adaptation of to various lesion microenvironments in infection induces various states of slow replication and non-replication and subsequent antibiotic tolerance. This non-heritable tolerance to treatment necessitates lengthy combination therapy. Therefore, it is critical to develop combination therapies that specifically target the different types of drug-tolerant cells in infection. As new tools to study drug combinations earlier in the drug development pipeline are being actively developed, we must consider how to best model the drug-tolerant cells to use these tools to design the best antibiotic combinations that target those cells and shorten tuberculosis therapy. In this review, we discuss the factors underlying types of drug tolerance, how combination therapy targets these populations of bacteria, and how drug tolerance is currently modeled for the development of tuberculosis multidrug therapy. We highlight areas for future studies to develop new tools that better model drug tolerance in tuberculosis infection specifically for combination therapy testing to bring the best drug regimens forward to the clinic.
Topics: Humans; Mycobacterium tuberculosis; Antitubercular Agents; Drug Therapy, Combination; Leprostatic Agents; Tuberculosis; Drug Tolerance
PubMed: 36733851
DOI: 10.3389/fcimb.2022.1085946 -
Methods in Molecular Biology (Clifton,... 2021Antibiotic tolerance and persistence allow bacteria to survive lethal doses of antibiotic drugs in the absence of genetic resistance. Despite the urgent need to address...
Antibiotic tolerance and persistence allow bacteria to survive lethal doses of antibiotic drugs in the absence of genetic resistance. Despite the urgent need to address these phenomena as a cause of clinical antibiotic treatment failure, studies on antibiotic tolerance and persistence are notorious for contradictory and inconsistent findings. Many of these problems are likely caused by differences in the methodology used to study antibiotic tolerance and persistence in the laboratory. Standardized experimental procedures would therefore greatly promote research in this field by facilitating the integrated analysis of results obtained by different research groups. Here, we present a robust and adaptable methodology to study antibiotic tolerance/persistence in broth cultures of Escherichia coli and Pseudomonas aeruginosa . The hallmark of this methodology is that the formation and disappearance of antibiotic-tolerant cells is recorded throughout all bacterial growth phases from lag after inoculation over exponential growth into early and then late stationary phase. In addition, all relevant experimental conditions are rigorously controlled to obtain highly reproducible results. We anticipate that this methodology will promote research on antibiotic tolerance and persistence by enabling a deeper view at the growth-dependent dynamics of this phenomenon and by contributing to the standardization or at least comparability of experimental procedures used in the field.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Drug Tolerance; Escherichia coli; Pseudomonas aeruginosa
PubMed: 34590249
DOI: 10.1007/978-1-0716-1621-5_2 -
Expert Review of Anti-infective Therapy Jul 2016
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Drug Tolerance; Humans; Microbial Sensitivity Tests
PubMed: 27227426
DOI: 10.1080/14787210.2016.1194754