Virulence and Resistance to Antifungal Therapies of Scopulariopsis Species

Scopulariopsis is an emerging opportunistic fungus characterized by its high resistance to antifungal therapies. We have developed a murine model of disseminated infection in immunosuppressed animals by intravenous inoculation of Scopulariopsis brevicaulis and Scopulariopsis brumptii, the most clinically relevant species, in order to evaluate their virulence and their responses to conventional antifungal treatments. Survival and tissue burden studies showed that S. brumptii was more virulent than S. brevicaulis. The three drugs tested, liposomal amphotericin B, posaconazole, and voriconazole, prolonged the survival of mice infected with S. brumptii, but none showed efficacy against S. brevicaulis. The different therapies were only able to modestly reduce the fungal burden of infected tissue; however, in general, despite the high serum levels reached, they showed poor efficacy in the treatment of the infection. Unfortunately, the most effective therapy for Scopulariopsis infections remains unresolved.     

E-ring isoprostane augments cholinergic neurotransmission in bovine trachealis via FP prostanoid receptors

Isoprostanes are prostaglandin-like molecules that accumulate in oxidative stress and also exert powerful biological effects on a wide variety of tissues. We investigated the effects of several different isoprostanes on contractions evoked by electrical field stimulation (EFS) in bovine trachealis, finding only 15-E2t-IsoP to augment those responses. Many others have shown that isoprostanes act on prostanoid receptors, usually those of the thromboxane-selective prostanoid receptor (TP) subtype, although some describe actions through prostaglandin E2-selective prostanoid receptor (EP) or less frequently through prostaglandin F2alpha-selective prostanoid receptors (FP). We used an extensive panel of highly selective agonists and antagonists of prostanoid receptors to characterize the ones through which 15-E2t-IsoP was acting here. Pretreatment with the FP-selective AL-8810 significantly inhibited the augmentation, whereas TP- and EP-selective blockers did not. On the other hand, the augmentation exerted by 15-E2t-IsoP was mimicked by submicromolar concentrations of the FP-selective agonists PGF2alpha and fluprostenol, as well as by micromolar concentrations of the TP-selective agonist U46619. The concentration-response relationship for exogenously added acetylcholine was not significantly affected by 15-E2t-IsoP, confirming that the effect of the latter on EFS-evoked responses was exerted prejunctionally (i.e., to enhance release of Ach from nerve endings), rather than a direct postjunctional effect via a receptor on the smooth muscle. Finally, we investigated whether the inhibitory (adrenergic) innervation was also modulated by 15-E2t-IsoP, finding EFS-evoked relaxations to be unaffected by the isoprostane. We conclude that 15-E2t-IsoP acts upon an FP receptor on the cholinergic nerve endings, leading to enhanced neurotransmission.     

Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse

A single exposure to cocaine rapidly induces the brief activation of several immediate early genes, but the role of such short-term regulation in the enduring consequences of cocaine use is poorly understood. We found that 4 h of intravenous cocaine self-administration in rats induced a transient increase in brain-derived neurotrophic factor (BDNF) and activation of TrkB-mediated signaling in the nucleus accumbens (NAc). Augmenting this dynamic regulation with five daily NAc BDNF infusions caused enduring increases in cocaine self-administration, and facilitated relapse to cocaine seeking in withdrawal. In contrast, neutralizing endogenous BDNF regulation with intra-NAc infusions of antibody to BDNF subsequently reduced cocaine self-administration and attenuated relapse. Using localized inducible BDNF knockout in mice, we found that BDNF originating from NAc neurons was necessary for maintaining increased cocaine self-administration. These findings suggest that dynamic induction and release of BDNF from NAc neurons during cocaine use promotes the development and persistence of addictive behavior.     

Facilitation of ejaculation induced by 8-OH-DPAT does not produce conditioned place preference in male rats

The serotonin 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) produces a drastic facilitation of ejaculation characterized by a significant reduction in the number of pre-ejaculatory intromissions and a shortening of ejaculation latency. In the present study, the authors evaluated whether this facilitation of ejaculation can induce a reward state assessed by conditioned place preference. Males treated with 0.1 or 1.0 mg/kg of 8-OH-DPAT showed a clear facilitation of ejaculation but did not develop conditioned place preference. These results clearly indicate that the pharmacological facilitation of ejaculation and the reduction of the number of intromissions does not necessarily make sex rewarding.     

Transitional cell tumor in a 12-year-old patient

Transitional cell papillomas, which are tumors of epithelial origin, are the most common urinary tract neoplasm in adults but are extremely rare in children. In both groups the main location is the bladder, often around one of the ureteric orifices. Symptoms vary widely but the most frequent is gross hematuria. Transitional cell papillomas are histologically low-grade tumors and total excision is considered curative. However the rate of recurrence in the literature is high, and there is a potential for a more aggressive type of tumor. We report the case of a 12-year-old girl who presented with a transitional cell papilloma near the right ureteric orifice and describe the etiopathogenesis, diagnosis, treatment and outcome of this entity.     

Quality assurance in mammography: artifact analysis.

Evaluation of mammograms for artifacts is essential for mammographic quality assurance. A variety of mammographic artifacts (i.e., variations in mammographic density not caused by true attenuation differences) can occur and can create pseudolesions or mask true abnormalities. Many artifacts are readily identified, whereas others present a true diagnostic challenge. Factors that create artifacts may be related to the processor (eg, static, dirt or excessive developer buildup on the rollers, excessive roller pressure, damp film, scrapes and scratches, incomplete fixing, power failure, contaminated developer), the technologist (eg, improper film handling and loading, improper use of the mammography unit and related equipment, positioning and darkroom errors), the mammography unit (eg, failure of the collimation mirror to rotate, grid inhomogeneity, failure of the reciprocating grid to move, material in the tube housing, compression failure, improper alignment of the compression paddle with the Bucky tray, defective compression paddle), or the patient (e.g., motion, superimposed objects or substances [jewelry, body parts, clothing, hair, implanted medical devices, foreign bodies, substances on the skin]). Familiarity with the broad range of artifacts and the measures required to eliminate them is vital. Careful attention to darkroom cleanliness, care in film handling, regularly scheduled processor maintenance and chemical replenishment, daily quality assurance activities, and careful attention to detail during patient positioning and mammography can reduce or eliminate most mammographic artifacts.