The potential of ligand binding proteins as drug carriers and delivery systems has recently sparked great interest. We investigated the potential of tear lipocalin (TL) to bind the antibiotic, rifampin, and the environmental conditions for controlled release. To determine if TL binds rifampin, gel filtration was used to isolate protein fractions of tears. Rifampin was detected by absorbance spectroscopy in the elution fractions containing TL. The bound complex of rifampin-TL generates optical activity at about 360 nm, indicating a unique conformation at the binding site. Rifampin has a higher affinity for TL (Kd=128 microM) than albumin. Rifampin is released from the TL calyx in acidic conditions and is displaced by palmitic acid. Autooxidation of free rifampin begins in minutes but is delayed by at least 3 h in the presence of TL. These properties are conducive to stabilization and delivery of rifampin to tubercles that are acidic and rich in fatty acids. These studies show the potential of TL as a carrier for rifampin with controlled release to a targeted environment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbadis.2003.11.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Safety and Effectiveness of BPaL-Based Regimens to Treat Multidrug-Resistant TB: First Experience of an Italian Tuberculosis Referral Hospital.
Antibiotics (Basel)
December 2024
Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, 00149 Rome, Italy.
: Tuberculosis (TB) is preventable and curable, but multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose significant challenges worldwide due to the limited treatment options, lengths of therapies, and high rates of treatment failure. The management of MDR-TB has been revolutionized by all oral anti-TB drug regimens that are likely to improve adherence and treatment outcomes. These regimes include bedaquiline (B), pretomanid (P), and linezolid (L) (BPaL), and moxifloxacin if resistance to fluoroquinolones is not detected (BPaLM).
View Article and Find Full Text PDFCharacteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.
Lancet Child Adolesc Health
February 2025
Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.
Methods: We conducted a systematic review and individual participant data meta-analysis.
How Often Is Rifampin Therapy Initiated and Completed in Patients With Periprosthetic Joint Infections?
Clin Orthop Relat Res
January 2025
Department of Medicine, Duke University, Durham, NC, USA.
Background: Rifampin therapy is indicated for the treatment of staphylococcal periprosthetic joint infection (PJI) in patients who have undergone debridement, antibiotics, and implant retention (DAIR) or one-stage revision as per the Infectious Diseases Society of America (IDSA) guideline. Given the well-established effectiveness of rifampin as adjunctive therapy in staphylococcal PJI, it is crucial to evaluate its utilization in practice and identify factors that contribute to its underuse or incomplete administration, as these deviations may undermine treatment efficacy and patient outcomes.
Questions/purposes: Among patients who met clear indications for rifampin use having undergone DAIR or one-stage revision for staphylococcal PJI, (1) what proportion of patients did not receive it? (2) What proportion of patients started it but did not complete the planned course? (3) Where documented in the medical record, what were the common reasons for not using it or prematurely discontinuing it, and in what percentage of the patients' charts was no reason given? (4) What proportion of patients were taking a medication that put them at risk for a drug-drug interaction (DDI)?
Methods: Using an institutional database, patients who underwent DAIR or revision arthroplasty for PJI from January 2013 to April 2023 were identified (n = 935).
Pretreatment attrition after rifampicin-resistant tuberculosis diagnosis with Xpert MTB/RIF or ultra in high TB burden countries: a systematic review and meta-analysis.
BMJ Glob Health
January 2025
Unit of HIV and Tuberculosis, Institute of Tropical Medicine Department of Clinical Sciences, Antwerpen, Belgium.
Introduction: The WHO endorsed the Xpert MTB/RIF (Xpert) technique since 2011 as initial test to diagnose rifampicin-resistant tuberculosis (RR-TB). No systematic review has quantified the proportion of pretreatment attrition in RR-TB patients diagnosed with Xpert in high TB burden countries.Pretreatment attrition for RR-TB represents the gap between patients diagnosed and those who effectively started anti-TB treatment regardless of the reasons (which include pretreatment mortality (death of a diagnosed RR-TB patient before starting adequate treatment) and/or pretreatment loss to follow-up (PTLFU) (drop-out of a diagnosed RR-TB patient before initiation of anti-TB treatment).
View Article and Find Full Text PDFFitness costs of Mycobacterium tuberculosis resistant to rifampicin is compensated by rapid Th2 polarization mediated by early and high IL-4 production during mice infection.
Sci Rep
January 2025
Experimental Pathology Department, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico.
It was a general belief that drug resistance in Mycobacterium tuberculosis (Mtb) was associated with lesser virulence, particularly rifampicin resistance, which is usually produced by mutations in the RNA polymerase Beta subunit (RpoB). Interestingly, this kind of bacterial mutations affect gene transcription with significant effects on bacterial physiology and metabolism, affecting also the bacterial antigenic constitution that in consequence can produce diverse immune responses and disease outcome. In the present study, we show the results of the Mtb clinical isolate A96, which is resistant to rifampicin and when used to infect BALB/c mice showed hypervirulence, apparently by rapidly polarization of the Th2 immune response through early and high production of IL-4.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!