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Since their introduction as pets several decades ago, ferrets have become an increasingly popular household pet. Great strides have been made in improving their diet and understanding common diseases (eg, insulinoma, hyperadrenocorticism, lymphoma) that affect them. With the frequency with which these conditions are seen, it sometimes is easy to forget that ferrets can be affected by other diseases. Some of these diseases, such as cryptococcosis, are known, but may be increasing in incidence and range, whereas others, such as hypothyroidism and pure red cell aplasia, may be underrecognized or underreported. This review highlights new and emerging diseases not already well reviewed in the literature., (Copyright © 2013 Elsevier Inc. All rights reserved.)

An international team including 12 laboratories from 11 independent biopharmaceutical companies in the United States and Switzerland was formed to evaluate the precision and robustness of imaged capillary isoelectric focusing for the charge heterogeneity analysis of monoclonal antibodies. The different laboratories determined the apparent pI and the relative distribution of the charged isoforms for a representative monoclonal antibody sample using the same capillary isoelectric focusing assay. Statistical evaluation of the data was performed to determine within and between laboratory consistencies and outlying information. The apparent pI data generated for each charged variant peak showed very good precision between laboratories with RSD values of less than 0.8%. Similarly, the RSD for the therapeutic monoclonal antibody charged variants percent peak area values are less than 11% across different laboratories using different analyst, different lots of ampholytes and multiple instruments. These results validate the appropriate use of imaged capillary isoelectric focusing in the biopharmaceutical industry in support of process development and regulatory submissions of therapeutic antibodies., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To determine the concentration of the pro-angiogenic vascular endothelial growth factor VEGF(165) (VEGF) and the anti-angiogenic VEGF(165b) in vitreous samples of patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in comparison to patients without retinal occlusive disease., Design: Experimental laboratory investigation., Methods: Vitreous samples were collected from patients undergoing surgery for arteriovenous dissection after BRVO, radial optic neurotomy after CRVO in the occlusion group, or macular pucker or macular hole in the control group. Concentrations of VEGF and VEGF(165b) were determined by ELISA and an ELISA-type antibody microarray., Results: Average vitreal concentration of VEGF was 8.6 ng/mL in the CRVO group and 2.0 ng/mL in the BRVO group as compared to 0.26 ng/mL in the control group. Average vitreal concentration of VEGF(165b) was 27 pg/mL in the CRVO group, 42 pg/mL in the BRVO group, and 49 pg/mL in the control group. In patients with CRVO and BRVO, the angiogenic balance was shifted towards angiogenic stimulation., Conclusion: The severity of RVO from BRVO to CRVO correlates with an increase of VEGF and the decrease of VEGF(165b), indicating a pro-angiogenic shift. Altering the ratio of VEGF(165b)/VEGF(165) might be a feasible approach for treating retinal occlusive diseases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Matrix metalloproteinases (MMPs) are central to tissue remodelling; however, little is known about the temporal pattern and differential regulation of hepatic MMP expression in the course of chronic human liver disease. Using quantitative reverse transcription-PCR ELISA assays, we studied hepatic mRNA expression of MMP-1, -2, -3, -7, -9, -10, -11, -13 and -14 in patients with chronic hepatitis C and hepatitis C virus-induced end-stage liver cirrhosis and controls. Results were compared with histology, hepatic expression of tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3, procollagen types I and IV, laminin, and with circulating protein levels of hyaluronate, TIMP-1 and -2 and MMP proenzymes, as measured by ELISA. The impact of the MMP-3(-1171) promoter polymorphism on hepatic MMP-3 expression was analysed. Hepatic mRNA expression data identified differentially regulated groups of MMPs during the course of chronic hepatitis C, showing either steadily increasing mRNA expression with disease progression (MMP-1, -2, -7 and -14) or transiently elevated expression (MMP-9, -11 and -13). The first group closely correlated to the parameters of fibrogenesis. Hepatic MMP-3 expression was unrelated to disease stage, but was determined by the MMP-3(-1171) promoter polymorphism. In conclusion, MMP expression during the course of chronic hepatitis C appears to be a closely regulated process, with different clusters of coordinately regulated MMP genes being identified.

Background: To clarify whether circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) can be used as serum markers of fibroproliferation in chronic liver diseases, we studied the expression of MMP-2 and MMP-9 in relation to TIMP-1 and TIMP-2 in peripheral blood mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMLs), and compared this expression to circulating concentrations and hepatic histology in patients with chronic active hepatitis C (CAH)., Methods: Quantitative reverse transcription-PCR/ELISA assays were performed for MMP and TIMP RNA, and corresponding circulating protein concentrations were studied by ELISA in 20 healthy controls, 40 patients with CAH, and 20 patients with hepatitis C-induced cirrhosis (Ci)., Results: MMP-2 mRNA was found almost exclusively in the liver, MMP-9 mRNA in leukocytes. TIMP RNA-equivalents were decreased in MNLs of CAH patients, but neither MMP-9 nor TIMP RNA expression showed any correlation to the extent of inflammation and fibrosis. MMP-2 and TIMP-1 protein concentrations were increased in Ci patients and showed a wide overlap in CAH patients and healthy controls. MMP-9 values were lower in CAH and Ci patients than in healthy controls. TIMP-2 values showed a wide overlap in all three groups. The MMP-2/TIMP-1 and MMP-9/TIMP-1 ratios were lower in Ci patients than in healthy controls; the MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios were not different. Circulating TIMP-1 and the MMP-2/TIMP-1 ratio correlated to the inflammatory activity in liver biopsies, but only the circulating MMP-2/TIMP-1 ratio also correlated with the degree of fibrosis., Conclusions: Peripheral blood cell expression of MMP-2, MMP-9, and TIMP revealed no correlation with the circulating concentrations of these proteins. Only the circulating MMP-2/TIMP-1 ratio correlated to the histological degree of fibrosis in hepatitis C and should be further evaluated as a progression marker in patients with chronic liver disease.

Transcription with fission yeast (Schizosaccharomyces pombe) RNA polymerase III (pol III) was studied in two different in vitro systems. Reactions performed with isolated nuclei gave rise to 5S and pre-tRNA molecules. Because the alpha-amanitin sensitivity of that reaction clearly differed from what has been observed with pol III enzymes of other eukaryotes, a cell-free S. pombe transcription extract was developed and analyzed with the homologous 7S L RNA (srp RNA; signal recognition particle RNA) gene. Synthesis of 7S L RNA was found to be sensitive to high concentrations of alpha-amanitin, with 50% reduction seen at 400 microg/ml of the toxin. However, even with very high alpha-amanitin concentrations, exceeding 1 mg/ml, no full inhibition of the S. pombe pol III enzyme could be obtained. Together, these results demonstrate that in contrast to the yeast Saccharomyces cerevisiae, pol III from S. pombe is sensitive to high concentrations of alpha-amanitin, yet with a clearly different dose response than that observed with the corresponding RNA polymerase of higher eukaryotes. Furthermore, while the S. pombe 7S L RNA gene was efficiently transcribed in HeLa cell extracts, the human 7S L RNA gene was not actively transcribed in the S. pombe system. This finding of divergent promoter structures of both genes was verified by the analysis of 5' deletion mutants of the S. pombe 7S L RNA gene.

Since late 1975, the King Faisal Specialist Hospital and Research Centre (KFSH&RC), a tertiary-care hospital in Saudi Arabia, has continuously collected data on its experience in oncology. With 22,836 cancer cases as a base, covering the years between 1976 and 1993, it is intended to present the hospital data obtained in this referral center as a prelude to the release of statistics from the Saudi Arabia National Cancer Registry (NCR) established in 1994. It will be interesting to see whether the data collected in the largest cancer referral center in the Kingdom will be comparable with national data when this becomes available. Our intent is to identify trends of referral and any possible bias in the data when compared to the NCR statistics of 1994.

In summary, having data from other service areas available in a relational clinical database could resolve many of the problems existing in today's registry systems. Uniting sophisticated information systems into a centralized database system could definitely be a corporate asset in managing the bottom line.