Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation.

The recently described species Candida dubliniensis has been recovered primarily from superficial oral candidiasis in HIV-infected patients. No clinically documented invasive infections were reported until now in this patient group or in other immunocompromised patients. We report three cases of candidemia due to this newly emerging Candida species in HIV-negative patients with chemotherapy-induced immunosuppression and bone marrow transplantation

Phage Displayed Short Peptides against Cells of Candida albicans Demonstrate Presence of Species, Morphology and Region Specific Carbohydrate Epitopes

Candida albicans is a commensal opportunistic pathogen, which can cause superficial infections as well as systemic infections in immuocompromised hosts. Among nosocomial fungal infections, infections by C. albicans are associated with highest mortality rates even though incidence of infections by other related species is on the rise world over. Since C. albicans and other Candida species differ in their susceptibility to antifungal drug treatment, it is crucial to accurately identify the species for effective drug treatment. Most diagnostic tests that differentiate between C. albicans and other Candida species are time consuming, as they necessarily involve laboratory culturing. Others, which employ highly sensitive PCR based technologies often, yield false positives which is equally dangerous since that leads to unnecessary antifungal treatment. This is the first report of phage display technology based identification of short peptide sequences that can distinguish C. albicans from other closely related species. The peptides also show high degree of specificity towards its different morphological forms. Using fluorescence microscopy, we show that the peptides bind on the surface of these cells and obtained clones that could even specifically bind to only specific regions of cells indicating restricted distribution of the epitopes. What was peculiar and interesting was that the epitopes were carbohydrate in nature. This gives insight into the complexity of the carbohydrate composition of fungal cell walls. In an ELISA format these peptides allow specific detection of relatively small numbers of C. albicans cells. Hence, if used in combination, such a test could help accurate diagnosis and allow physicians to initiate appropriate drug therapy on time

Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications

ABSTARCT: Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies

Investigation into the molecular mechanisms of itraconazole resistance in Candida dubliniensis

THESIS 7380Candida dubliniensis is a recently identified yeast species primarily associated with oral carriage and infection in HIV-infected individuals. Previous studies have shown that only a small number of clinical isolates are resistant to the commonly used antifungal drug fluconazole and that stable resistance to fluconazole can be induced in vitro in this species. Overexpression of the multidrug resistance gene CdMDR1 has previously been shown to be a major contributor to resistance in fluconazole-resistant isolates and in vitro-generated derivatives. However, given the inability of CdMdr1p to mediate the transport of other azole drugs such as itraconazole and the high prevalence of nonsense mutations in the multidrug resistance gene CdCDR1, the general aim of the present study was to investigate the prevalence and molecular basis of itraconazole resistance in C. dubliniensis

Opioid misuse.

PHARMACOLOGY OF OPIOIDS: The term ‘opioids’ refers to a class of psychoactive substances derived from the poppy plant (including opium, morphine and codeine), as well as semi-synthetic forms (including heroin) and synthetic compounds (including methadone and buprenorphine) with similar properties. Illicit use of opioids generally involves injecting, or inhaling the fumes produced by heating the drug. Opioids have many effects on the brain, mediated through specific receptors. The key opioid receptor subtype is μ, which mediates euphoria, as well as respiratory depression, and is the main target for opioids while the κ receptor is involved in mood regulation. Soon after injection (or inhalation), heroin metabolises into morphine and binds to opioid receptors. This is subjectively experienced as a euphoric rush, normally accompanied by a warm flush, dry mouth, and sometimes nausea, vomiting and severe itching. As the rush wears off, drowsiness, and slowing of cardiac function and breathing (sometimes to the point of death in an overdose), persist for several hours. The effects of methadone are similar but more drawn out and therefore less intense. OPIOID MISUSE AND DEPENDENCE: Misuse Drug misuse is a relapsing and remitting condition often involving numerous treatment episodes over several years. Drug misuse has a negative impact on health or functioning and may take the form of drug dependence, or be part of a wider spectrum of problematic or harmful behaviour. Many people who misuse opioids also misuse a range of other substances concurrently and regularly. Alcohol misuse is also common in people who misuse drugs. Dependence The WHO ICD-10 Classification of Mental and Behavioural Disorders defines six criteria for substance use dependence. Dependence is diagnosed if three or more of these criteria have been experienced or exhibited together at some time during the previous year: • Strong desire or compulsion to take a substance • Difficulty in controlling substance use • Presence of a physiological withdrawal state • Tolerance of the use of the drug (increased doses are needed to achieve effects originally produced by lower doses) • Neglect of alternative pleasures and interests • Persistent use of the drug, despite harm to oneself and others While the initiation of drug use does not lead inevitably to dependence over the long term, a number of factors can potentiate this developmental course. Earlier initiation of drug use increases the likelihood of daily use, which in turn results in a greater likelihood of dependence....

Use of prescribed drugs to treat alcohol addiction.

Alcohol-dependent patients might require medically prescribed drugs to help them in the initial stages of treatment or/and to prevent relapses. The main types of drug used in the treatment of alcohol addiction are: Detoxification: • Chlordiazepoxide: Chlordiazepoxide is indicated for the management of alcohol withdrawal. It is a benzodiazepine used for the short-term (2-4 weeks) symptomatic treatment of severe and disabling anxiety, which is a common symptom during the withdrawal period. It is contraindicated in case of myasthenia gravis, severe respiratory insufficiency, sleep apnoea and severe hepatic insufficiency. • Other benzodiazepines such as alprazolam are also indicated for anxiety, but like other benzodiazepines only when the disorder is severe, disabling or subjecting the individual to extreme distress. Detoxification from alcohol dependence using another sedative such as benzodiazepines follows the same principle as detoxification from nicotine dependence using nicotine replacement or from opioid dependence using methadone or buprenorphine. However, in the treatment of patients dependent on alcohol or other sedatives, appropriate detoxification is particularly critical because the sedative withdrawal syndrome is potentially life-threatening. Preventing relapse (see also Table 1 on IMT website) • Acamprosate... • Disulfiram... • Naltrexone..