Most long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. Here we focus on a set of intergenic lncRNAs in fission yeast. Deleting one of these lncRNAs exhibited a clear phenotype: drug sensitivity. Detailed analyses of the affected locus revealed that transcription of the nc-tgp1 lncRNA regulates drug tolerance by repressing the adjacent phosphate-responsive perm...

Mycobacterium tuberculosis (Mtb) causes tuberculosis (TB). The treatment of TB requires administration of multiple drugs for long durations because of the unusual drug tolerance of Mtb. The phenotypic drug tolerance of genetically drug-susceptible Mtb in humans can be explained by its ability to form biofilms. Recent studies from different laboratories suggest that Mtb forms biofilms that harbo...

A model of "overdose" deaths among heroin addicts is proposed which emphasizes recent findings concerning the contribution of drug-associated environmental cues to drug tolerance. Results of animal experiments performed to evaluate this model suggest that conditioned drug-anticipatory responses, in addition to pharmacological factors, affect heroin-induced mortality.

Opiates, chiefly morphine, are commonly known as the best drugs for relief of pain, but due to development of tolerance and the physical or mental dependency the use of these drugs are restricted. Several neuroendocrine complications including diabetes change the antinociception of morphine and the development of tolerance and dependency to this drug. The withdrawal signs in diabetic rats signi...

Antibiotic tolerance, the capacity of genetically susceptible bacteria to survive the lethal effects of antibiotic treatment, plays a critical and underappreciated role in the disease burden of bacterial infections. Here, we take a pathogen-by-pathogen approach to illustrate the clinical significance of antibiotic tolerance and discuss how the physiology of specific pathogens in their infection...

Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effect...

The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understandi...

First, a couple of definitions and distinctions: "abuse" according to the American Psychiatric Association describes a pattern of use that causes impairment of social or occupational functioning. Compare that to "dependence," characterized by either tolerance (a need for increasing amounts of a drug, over time, to achieve the same effect) or withdrawal symptoms. "Addiction" is defined by compul...

First, a couple of definitions and distinctions: "abuse" according to the American Psychiatric Association describes a pattern of use that causes impairment of social or occupational functioning. Compare that to "dependence," characterized by either tolerance (a need for increasing amounts of a drug, over time, to achieve the same effect) or withdrawal symptoms. "Addiction" is defined by compul...

The value of drug treatment in angina pectoris can be accurately assessed by using reproducible treadmill exercise under controlled conditions. A "training" period to allow patients to become completely familiar with the test is of great importance, because during this period effort tolerance usually increases irrespective of drug therapy. The change in effort tolerance after pronethalol or pro...