Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called 'Z' mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols. © Springer Science+Business Media B.V. 2008.

Development and validation of a lateral flow device for the detection of nicarbazin contamination in poultry feeds

Concentrations of the coccidiostat nicarbazin as low as 2 mg/kg in feed can result in violative drug residues arising in poultry liver. A lateral flow device (LFD) was developed for the detection of contaminating concentrations of nicarbazin following solvent extraction of poultry feeds. Test results, as determined by both visual and instrumental measurement, are available within minutes. For 22 feed samples, nicarbazin-free and fortified at 2 mg/kg, the % relative inhibition ranged from 0 to 45% and from 53 to 85%, respectively. Nicarbazin contamination at the critical concentration (2 mg/kg) can be determined in all cases providing the sampling is representative. A wide range of feed samples taken at a mill that incorporated nicarbazin into poultry feed were analyzed. Data generated for these samples by both the LFDs and a mass spectrometric method were compared, and a significant correlation was achieved.

Detection of synthetic glucocorticoid residues in cattle tissue and hair samples after a single dose administration using LC-MS/MS

A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the detection of several synthetic glucocorticoids in kidney, muscle and hair samples of cattle after a single intramuscular injection is described. After a dichloromethane wash of the hair samples, analytes were released from the hair matrix by enzymatic digestion. Muscle samples were also digested enzymatically using proteinase, while kidney samples were deconjugated by Helix pomatia juice. These preliminary steps were followed by a methanol extraction and a solid phase extraction (SPE) clean up step for all matrices. Chromatographic separation was achieved on a Hypersil Hypercarb column and MS/MS data were obtained in the multiple reaction monitoring mode using negative electrospray ionization. The developed protocols were evaluated by assessing residue concentrations in muscle, kidney and hair samples of thirteen calves, treated with a particular intramuscular injection of glucocorticoid. The lowest residue levels were found in muscle samples (approximately 5% of the residue levels in kidney), while high residue levels were obtained in hair samples. Hair is an interesting matrix since the sampling is non-invasive and the drugs may stay incorporated for a longer period of time. (C) 2004 Elsevier B.V. All rights reserved.

Liver fluke (Fasciola hepatica)-derived peptides activate rat peritoneal mast cells

Short peptides with sequences derived from those found in the tegumental antigen of Fasciola hepatica have been synthesised. Incubation of some of these peptides with rat peritoneal mast cells resulted in the degranulation of the cells as measured by a histamine release assay. This activity was shown to be associated with the proline-lysine-proline motif, which is responsible for the induction of mast cell degranulation by the mammalian bioactive peptide substance P. Studies on the mode of action of the fluke-derived peptide indicated that it was operating through the same biochemical pathways as substance P. The implications of these findings for the development of immune responses during parasite infections are discussed. (C) 2003 Elsevier Science B.V. All rights reserved.

Understanding genetic diversity of the liver fluke Fasciola hepatica

Economical breeding is important to obtain maximum gain from the breeding in the animal sector. The economic loss has to be eliminated or should be minimized. The liver fluke, Fasciola hepatica, present mostly in sheep and dairy cattle affect the yield of animals and even cause their death. To eliminate or minimize the impact of these parasites on the animals, it is important to understand the genetic diversity of the liver fluke populations and the relationship between parasite and host at regional bases. This research was carried out to determine diversity by sequence analysis of the mitochondrial ND1 gene and ribosomal ITS1 region.

Density-viscosity product of small-volume ionic liquid samples using quartz crystal impedance analysis

Quartz crystal impedance analysis has been developed as a technique to assess whether room-temperature ionic liquids are Newtonian fluids and as a small-volume method for determining the values of their viscosity-density product, rho eta. Changes in the impedance spectrum of a 5-MHz fundamental frequency quartz crystal induced by a water-miscible room-temperature ionic liquid, 1-butyl-3-methylimidazolium. trifluoromethylsulfonate ([C(4)mim][OTf]), were measured. From coupled frequency shift and bandwidth changes as the concentration was varied from 0 to 100% ionic liquid, it was determined that this liquid provided a Newtonian response. A second water-immiscible ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C(4)mim][NTf2], with concentration varied using methanol, was tested and also found to provide a Newtonian response. In both cases, the values of the square root of the viscosity-density product deduced from the small-volume quartz crystal technique were consistent with those measured using a viscometer and density meter. The third harmonic of the crystal was found to provide the closest agreement between the two measurement methods; the pure ionic liquids had the largest difference of similar to 10%. In addition, 18 pure ionic liquids were tested, and for 11 of these, good-quality frequency shift and bandwidth data were obtained; these 12 all had a Newtonian response. The frequency shift of the third harmonic was found to vary linearly with square root of viscosity-density product of the pure ionic liquids up to a value of root(rho eta) approximate to 18 kg m(-2) s(-1/2), but with a slope 10% smaller than that predicted by the Kanazawa and Gordon equation. It is envisaged that the quartz crystal technique could be used in a high-throughput microfluidic system for characterizing ionic liquids.