Progress in treatment of ANCA-associated vasculitis

Autoantibodies to neutrophil cytoplasmic antigen-associated vasculitis (AAV) is characterised by inflammation of blood vessels. The introduction of immunosuppressive therapy with glucocorticoids and cyclophosphamide transformed AAV from a fatal condition to a largely treatable condition. Over the past 30 years, considerable progress has been made refining immunosuppressive regimens with a focus on minimising toxicity. There is, however, a high unmet need in the treatment of AAV. A proportion of patients are refractory to current therapies; 50% experience a relapse within 5 years and treatment toxicity contributes to mortality and chronic disability. As knowledge of the pathogenesis of vasculitis grows, it is mirrored by the availability of biological agents, which herald a revolution in the treatment of vasculitis. Lymphocyte-targeted and cytokine-targeted agents have been evaluated for the treatment of AAV and are entering the routine therapeutic arena with the potential to improve patient outcomes. As rare diseases, treatment advances in vasculitis depend on international collaborative research networks both to establish an evidence base for newer agents and to develop recommendations for patient management.     

Combining Affymetrix microarray results

Background  

As the use of microarray technology becomes more prevalent it is not unusual to find several laboratories employing the same microarray technology to identify genes related to the same condition in the same species. Although the experimental specifics are similar, typically a different list of statistically significant genes result from each data analysis.     

A review of curcumin as a biological stain and as a self-visualizing pharmaceutical agent

Curcumin has been widely used to color textiles but, unlike other natural dyes such as hematoxylin or saffron, it rarely has been discussed as a biological stain. Aspects of the physicochemistry of curcumin relevant to biological staining and self-visualization, i.e., its acidic properties, lipophilicity, metal and pseudometal complexes, and optical properties, are summarized briefly here. Reports of staining of non-living biological specimens in sections and smears, both fixed and unfixed, including specimens embedded in resin, are summarized here. Staining of amyloid, boron and chromatin are outlined and possible reaction mechanisms discussed. Use of curcumin as a vital stain also is described, both in cultured monolayers and in whole organisms. Staining mechanisms are considered especially for the selective uptake of curcumin into cancer cells. Staining with curcumin labeled nanoparticles is discussed. Toxicity and safety issues associated with the dye also are presented.     

Glyoxal fixation: how it works and why it only occasionally needs antigen retrieval

Over the past 13 years, glyoxal has become the leading alternative to formaldehyde as a histological fixative because of its low inhalation risk, faster reaction rate and selective control over crosslinking. The latter attribute is especially important, because most of the difficulties relating to use of formaldehyde-fixed specimens for immunohistochemistry stem from its aggressive crosslinking behavior. With suitable catalysts or other reaction accelerators, glyoxal forms 2-carbon adducts with nearly all end groups in proteins and carbohydrates, leaving most of them unimpaired for subsequent immunohistochemical demonstration. Only arginine is seriously impaired by the formation of imidazoles, which is the basis for the well known arginine blockade method using glyoxal. A special glyoxal-specific antigen retrieval method using high pH and high temperature effectively reverses the blockade and restores immunoreactivity. Other methods for antigen retrieval are rarely beneficial and in most cases damage the specimen. Special stains work well, except silver methods for Helicobacter pylori. Routine hematoxylin and eosin preparations exhibit clarity and cellular detail rarely seen with formaldehyde.     

Accomplishments of the Trustees and laboratory staff of the Biological Stain Commission, 2002–2013

During the 12 years from 2002 to 2013, the Trustees and laboratory personnel of the Biological Stain Commission (BSC) can claim many accomplishments. These accomplishments are itemized under 11 categories: continuous publication of the official journal, Biotechnic & Histochemistry; production of four special issues of Biotechnic & Histochemistry devoted to specific dyes or stains; standardization of staining and dye purity; mechanisms of staining and prediction of dye behavior; publication of books or book chapters; effects of fixation and processing on staining; cancer research; immunohistochemistry; BSC Laboratory activities; miscellaneous publications; and administrative accomplishments.     

Micronutrients and macronutrients and parameters of antioxidative ability in saliva of women

There were two aims of the present study: (1) to evaluate changes of superoxide dismutase (SOD) activity and total antioxidative status measured as the ferric reducing ability of plasma (FRAP) concentration in saliva of pregnant women during the first, second, and third trimesters of singleton uncomplicated pregnancy and (2) to assess possible relations among SOD, FRAP, and intake of macronutrients and micronutrients in daily nutritional rations (DNRs) during pregnancy. Forty pregnant women aged 27.1+/-5.4 yr (examined group) and 40 healthy women (the control group) were recruited for this study. The relationship between FRAP and SOD in saliva and the intake of macronutrients (proteins, carbohydrates, total fat, saturated fatty acid, monounsaturated fatty acids, polyunsaturated fatty acids), minerals (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn), and vitamins (A, C, E, B1, B2, B6, PP) in DNR was evaluated by clustering analysis with Ward's grouping method. During pregnancy, FRAP and SOD values were lower than in the controls, but only for FRAP were the differences statistically significant (p < 0.001). For the whole pregnancy period, cluster analysis identified two major clusters for which the differentiating variables were SOD and retinoids intake, but different patterns for each trimester of pregnancy were revealed. The following were concluded: (1) FRAP values were the lowest in the second trimester. It suggests that in this trimester of uncomplicated pregnancy, women might be not fully adapted to increased demands for antioxidative mechanisms. (2) Cluster analysis showed that there were no statistical relationships between the intake of micronutrients and macronutrients in DNRs and the SOD or FRAP level in the saliva of pregnant women.     

Short repetitive sequences in green algal mitochondrial genomes: potential roles in mitochondrial genome evolution

Current data on green algal mitochondrial genomes suggest an unexpected dichotomy within the group with respect to genome structure, organization, and sequence affiliations. The present study suggests that there is a correlation between this dichotomy on one hand and the differences in the abundance, base composition, and distribution of short repetitive sequences we observed among green algal mitochondrial genomes on the other. It is conceivable that the accumulation of GC- rich short repeated sequences in the Chlamydomonas-like but not Prototheca-like mitochondrial genomes might have triggered evolutionary events responsible for the distinct series of evolutionary changes undergone by the two green algal mitochondrial lineages. The similarity in base composition, nucleotide sequence, abundance, and mode of organization we observed between the short repetitive sequences present in Chlamydomonas-like mitochondrial genomes on one hand and fungal and vertebrate homologs on the other might extend to some of the roles that the short repetitive sequences have been shown to have in the latter. Potential involvements we propose for the short repetitive sequences in the evolution of Chlamydomonas-like mitochondrial genomes include fragmentation and scrambling of the ribosomal-RNA-coding regions, extensive gene rearrangements, coding-region deletions, surrogate origins of replication, and chromosomal linearization.      

A Retrospective Study of Mortality in Varanid Lizards (Reptilia:Squamata:Varanidae) at the Bronx Zoo: Implications for Husbandry and Reproductive Management in Zoos

Varanid lizards have been maintained in zoological parks for more than a century, yet few studies to date have attempted to pinpoint significant health issues affecting their management or areas of captive husbandry that are in need of improvement. In an effort to identify and better understand some of the husbandry‐related challenges and health issues specifically affecting varanids in zoos, this study examined mortality in 16 species maintained at the Bronx Zoo between 1968 and 2009. Out of 108 records reviewed, complete necropsy reports were available for 85 individuals. Infection‐related processes including bacterial (15.3%), protozoal (12.9%), nematode (9.4%), and fungal (3.5%) infections accounted for the greatest number of deaths (47.1%). Noninfectious diseases including female reproductive disorders (7.1%), neoplasia (7.1%), gout (10.8%), and hemipenal prolapse (1.3%) accounted for 29.4% of deaths. Multiple disease agents were responsible for 5.9% of deaths, and a cause for death could not be determined for 17.7% of individuals. Reproductive complications accounted for 11.5% of female deaths, but were identified in 23.1% of females. Although not necessarily the cause for death, gout was present in 18.8% of individuals. Differences in mortality between species, genders, and origin (captive‐bred vs. wild‐caught) were also evaluated. The results of this study corroborate earlier findings that identify bacterial infections, neoplasia, female reproductive disorders, gout, and endoparasitism as major sources of mortality in captive varanids. In light of these results, we discuss potential etiologies and offer recommendations for improving captive management practices in zoos. Zoo Biol. 32:152–162, 2013. © 2012 Wiley Periodicals, Inc.