Cardiac toxicity of the echinocandins: chance or cause and effect association?

WHAT IS KNOWN AND OBJECTIVE: Fungal infections pose a constant risk to critically ill and immunosuppressed patients. The echinocandin antifungals give practitioners an arsenal of agents with apparently lower toxicity relative to older agents. The objective of this commentary is to review the cardiac toxicity of the echinocandin antifungals in the light of recent evidence and published case reports. COMMENT: Three case reports detail cardiac decompensation following the initiation of anidulafungin and caspofungin and corroborate ex vivo laboratory results, in which rat hearts exposed to anidulafungin and caspofungin had significantly decreased cardiac contractility. Our hypothesized mechanism of toxicity of anidulafungin and caspofungin is mitochondrial toxicity. WHAT IS NEW AND CONCLUSION: The clinical corroboration of the ex vivo work presented above highly suggests that the cardiac toxicity seen with some of the echinocandin antifungals is a cause and effect pattern, not a chance finding.

Intact olfactory memory in the 5xFAD mouse model of Alzheimer's disease from 3 to 15 months of age.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes profound cognitive dysfunction. Deficits in olfactory memory occur in early stages of AD and may be useful in AD diagnosis. The 5xFAD mouse is a commonly used model of AD, as it develops neuropathology, cognitive and sensori-motor dysfunctions similar to those seen in AD. However, olfactory memory dysfunction has not been studied adequately or in detail in 5xFAD mice. Furthermore, despite sex differences in AD prevalence and symptom presentation, few studies using 5xFAD mice have examined sex differences in learning and memory. Therefore, we tested olfactory memory in male and female 5xFAD mice from 3 to 15 months of age using a conditioned odour preference task. Olfactory memory was not impaired in male or female 5xFAD mice at any age tested, nor were there any sex differences. Because early-onset impairments in very long-term (remote) memory have been reported in 5xFAD mice, we trained a group of mice at 3 months of age and tested olfactory memory 90 days later. Very long-term olfactory memory in 5xFAD mice was not impaired, nor was their ability to perform the discrimination task with new odourants. Examination of brains from 5xFAD mice confirmed extensive Aß-plaque deposition spanning the olfactory memory system, including the olfactory bulb, hippocampus, amygdala and piriform cortex. Overall this study indicates that male and female 5xFAD mice do not develop olfactory memory deficits, despite extensive Aß deposition within the olfactory-memory regions of the brain.

Clinical characteristics of canine fibrocartilaginous embolic myelopathy (FCE): a systematic review of 393 cases (1973-2013).

Fibrocartilaginous embolic myelopathy (FCE) is common in dogs; however, there is conflicting information in the veterinary literature regarding clinical characteristics and data on recovery in severe cases is sparse. A systematic review of canine FCE was performed to delineate the natural history of this disease. 322 previously reported cases and 71 previously unreported cases were identified for inclusion. Source publications were identified via PubMed central search and by references from review articles. Previously unreported cases were identified via computerised medical records search at two veterinary institutions. FCE was most common in middle-aged large breed dogs (30 per cent); however, the miniature schnauzer was the most frequently reported individual breed and small breeds comprised 24 per cent of all reported cases. The most common neuroanatomical localisation was a T3-L3 myelopathy (33.1 per cent). Prognosis for recovery of ambulation was good to excellent with 85 per cent of cases regaining the ability to walk unassisted, most within 3 weeks. Persistent neurological deficits were common in patients that recovered ambulation (49.1 per cent). When nociception was absent in the affected limbs at initial presentation, rate of recovery was lower (10 per cent); however, this data is likely biased by limited follow-up in more severe cases. Future prospective studies should evaluate prognosis for more severely affected patients.

Spirochetes: vaccines, animal models and diagnostics.

The detailed characterization of various proteins from spirochetes using molecular biology techniques has made possible new approaches to vaccine and diagnostic development that are described in this session. The importance of animal models was emphasized and illustrated.

Spectral karyotyping combined with locus-specific FISH simultaneously defines genes and chromosomes involved in chromosomal translocations.

Genes that play roles in malignant transformation have often been found proximate to cancer-associated chromosomal breakpoints. Identifying genes that flank chromosomal reconfigurations is thus essential for cancer cytogenetics. To simplify and expedite this identification, we have developed a novel approach, based on simultaneous spectral karyotyping and fluorescence in situ hybridization (FISH) which, in a single step, can identify gross chromosomal aberrations as well as detect the involvement of specific loci in these rearrangements. Signals for specifically queried genes (FISH probe) were easily detectable in metaphase cells, together with the signals from painted chromosomes (spectral karyotyping probes). The concentration and size of the FISH probes could cover a wide range and still be used successfully. Some of the nucleotide-bound dyes used for the labeling, as Cy3, Spectrum Orange, Alexa 594, Texas Red, and Rhodamine 110, were particularly efficient. More than one gene can be queried in the same metaphase, because multiple FISH probes could be hybridized simultaneously. To demonstrate this technique, we applied it to the myeloma cell line Karpas 620, which has numerous chromosomal rearrangements. The approach that we present here will be particularly useful for the analysis of complex karyotypes and for testing hypotheses arising from cancer gene expression studies. Published 2000 Wiley-Liss, Inc.