Vasovagal tonus index (VVTI) as an indirect assessment of remission status in canine multicentric lymphoma undergoing multi-drug chemotherapy

Vasovagal tonus index (VVTI) is an indirect measure of heart rate variability and may serve as a marker of disease severity. Higher heart rate variability has predicted lower tumour burden and improved survival in humans with various tumour types. The purpose of this pilot study was to evaluate VVTI as a biomarker of remission status in canine lymphoma. The primary hypothesis was that VVTI would be increased in dogs in remission compared to dogs out of remission. Twenty-seven dogs were prospectively enrolled if they had a diagnosis of intermediate to high-grade lymphoma and underwent multidrug chemotherapy. Serial electrocardiogram data were collected under standard conditions and relationships between VVTI, remission status and other clinical variables were evaluated. VVTI from dogs in remission (partial or complete) did not differ from dogs with fulminant lymphoma (naive or at time of relapse). Dogs in partial remission had higher VVTI than dogs in complete remission (p = 0.021). Higher baseline VVTI was associated with higher subsequent scores (p < 0.001). VVTI also correlated with anxiety level (p = 0.03). Based on this pilot study, VVTI did not hold any obvious promise as a useful clinical biomarker of remission status. Further investigation may better elucidate the clinical and prognostic utility of VVTI in dogs with lymphoma

ChimeriVax-West Nile Virus Live-Attenuated Vaccine: Preclinical Evaluation of Safety, Immunogenicity, and Efficacy

The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN(02) vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans

Atrichia with papular lesions resulting from mutations in the rhesus macaque (Macaca mulatta) hairless gene.

Atrichia with papular lesions (APL) is a rare form of hair loss with an autosomal recessive mode of inheritance that is characterized by the absence of normal hair follicles, and formation of intradermal cystic structures. Mutations in the hairless (hr) gene in mice and humans have been implicated in the development of this phenotype. Hairless is a putative transcription factor containing a single zinc-finger DNA binding domain, with restricted expression in brain and skin. Here, we describe the complete hr cDNA sequence from the rhesus macaque (Macaca mulatta) and report the identification of a compound heterozygous mutation in a hairless rhesus macaque born from unrelated parents. Cutaneous biopsy samples from the affected macaque revealed abnormalities, including the replacement of normal hair follicles with dermal cysts and comedones, reminiscent of the skin phenotype observed in hairless mice and humans with APL

Images of tissue inflammation and <i>B. burgdorferi</i> antigen in tissues from animals treated in the late, disseminated phase (Experiment 1).

<p>For antigen detection, samples of tissue were stained for fluorescent detection (IFA) with anti-<i>B. burgdorferi</i> monoclonal (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029914#s4" target="_blank">Materials and Methods</a>) antibody. (A) Hematoxylin &Eosin stain showing monocytic and lymphocytic infiltrate in a heart section (20×) of a treated animal (AM38). (B) Image of positive IFA staining from the heart tissue of the same animal.</p

Solar buildings and the urban environment

SOlutions for Low Energy Neighbourhood

Detection of <i>B. burgdorferi</i> DNA (PCR), antigen by immunofluorescence assay (IFA), anti-C6 serum antibody (C6), <i>B. burgdorferi</i> RNA (RT-PCR), and inflammatory lesions (by Hematoxylin and Eosin stain (H&E)) in all animals at postmortem, 6 to 12 months after the end of the antibiotic treatment (Experiment 1).

<p>b, brain; bl, bladder; drg, dorsal root ganglia; h, heart; l, lung;</p><p>m, meninges; s, spleen.</p><p>(uninf.): animals not inoculated with <i>B. burgdorferi</i>.</p><p>NA: sample not available.</p

Nucleic acid detection of <i>B. burgdorferi</i> (Experiment 2).

<p>Detection by PCR or RT-PCR using primers for the indicated genes from: A) skin biopsy samples; B) xenodiagnostic ticks; C) organ tissue culture pellets; and D) directly from tissues known to harbor the spirochetes. Animal numbers in <b>bold</b> are of those that were treated. Asterisks indicate clear positive amplimers.sk = skin; h t = heart; bl = bladder; spl = pleen. Labels include: M = marker (100 bp ladder); (+) = <i>B.burgdorferi</i>, strain B31 DNA/RNA; ssc = spirochete strain negative control (<i>Bb</i> strain JD1 DNA); ntc = no template control; tnc = tick negative control; uim = uninfected monkey DNA/RNA.</p

Reciprocal end-point dilution titers of anti-C6 antibodies in antibiotic-treated^* (<b>bold</b>) and untreated macaques infected with <i>B. burgdorferi</i> (Experiment 2).

<p>*treatment was given during weeks 16–20.</p