Transdermal absorption of a liposome-encapsulated formulation of lidocaine following topical administration in cats

OBJECTIVE: To determine plasma disposition after dermal application of a liposome-encapsulated formulation of lidocaine in cats. ANIMALS: 6 healthy adult cats with a mean (+/- SD) body weight of 4.1 +/- 0.44 kg. PROCEDURE: CBC determination and biochemical analysis of blood samples were performed for all cats. Cats were anesthetized by use of isoflurane, and catheters were placed IV in a central vein. The next day, blood samples were obtained from the catheters before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma concentrations of lidocaine were analyzed with a high-performance liquid chromatography assay. Results-Two cats had minimal transdermal absorption of lidocaine, with lidocaine concentrations below the sensitivity of the assay at all but 1 or 2 time points. In the other 4 cats, the median maximum plasma concentration was 149.5 ng/ml, the median time to maximum plasma concentration was 2 hours, and the median area under the concentration versus time curve from zero to infinity was 1014.5 ng.h/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Maximum plasma concentrations of lidocaine remained substantially below toxic plasma concentrations for cats. On the basis of these data, topical administration of a liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be safe for use in healthy adult cats.     

DNA fingerprinting of Australian isolates of Mycobacterium avium subsp paratuberculosis using IS900 RFLP

OBJECTIVES: To evaluate additional restriction enzymes for IS900 RFLP of Mycobacterium avium subsp paratuberculosis and examine the genetic diversity among Australian isolates for epidemiological studies of Johne's disease. DESIGN AND PROCEDURE: Seventy-one isolates of M paratuberculosis from cattle, sheep, goat, alpaca and rhinoceros in six Australian States and the Northern Territory, reference strains and reference DNA from previously characterised strains were tested for genetic variation. Bst EII, Pvu II and Pst I restriction enzymes were used, and four others (Bam HI, Alu I, Xho I and Dra I) were assessed for their ability to detect polymorphisms. Multiple isolates from some animals were tested. RESULTS: Bam HI, was the most effective enzyme for identifying polymorphisms (12 types), followed by Bst EII (11 types). Both Pvu II and Pst I were relatively ineffectual. Fifteen different types were identified, 12 in clinical isolates. Most isolates were cattle (C) strains and fell into the C1 (n = 28) and C3 (n = 32) groupings. All isolates from alpaca were type C1, and bovine isolates were commonly C1 (n = 15) or C3 (n = 28). All of the sheep were infected with sheep (S) strains; no S strains were identified in cattle. Two of six isolates from one animal had single band differences. CONCLUSION: The epidemiological features of M paratuberculosis in Australia are similar to those reported in New Zealand, where cattle and sheep are commonly infected with different strains. However, because of the lack of polymorphism identified within the major groups, it is unlikely that DNA fingerprinting will have a significant role in epidemiological studies of Johne's disease, unless an unusual strain in being studied.     

Pharmacogenetics.

Pharmacogenetics, the study of genetic determinants of response to drug therapy, is likely the ultimate way to establish the right drug and dose for each patient, thereby optimizing efficacy and minimizing toxicity. Despite the fact that this branch of pharmacology is still in its infancy as a science, a number of important discoveries have already contributed to improved pharmacotherapy in human and veterinary patients.     

The effects of poplar (P. trichocarpa × deltoides) on soil biological properties in a silvoarable system

A silvoarable experimental site in Buckinghamshire, England combined rows of poplar trees with an arable rotation. Soil properties were investigated using soil carbon and the bodysize of invertebrates. Four years after establishment, the soil within and 1 m from the tree rows has significantly higher soil organic matter and invertebrate populations. These effects do not extend far beyond the crown diameter.     

Long term effects of enhanced nitrogen deposition on a lowland dry heath in southern Britain

Experimental additions of ammonium sulphate to a nitrogen-poor dry heathland have been carried out since 1989. There are four nitrogen treatments: a control (receiving artificial rain only), a low treatment which receives an additional 7.7 kg N ha^?1 yr^?1, a high treatment receiving 15.4 kg N ha^?1 yr^?1 and an alternating treatment which receives either the control or the high nitrogen additions, in alternate years. The estimated background deposition at the study site is 13–18 kg N ha^?1 yr^?1, a value similar to the critical load that has been suggested for the conversion of lowland heath to grassland. Over the past 5 years there have been significant stimulations in shoot growth, flowering, canopy density and litter production. Flowering, in particular, strongly reflects nitrogen additions in the alternating treatment. Current models of the response of dry Calluna heathlaud to enhanced nitrogen deposition suggest that higher tissue nitrogen levels will occur and will be accompanied by heightened sensitivity to secondary stresses. This may in turn lead to canopy breakdown and replacement by grassland. The application of nitrogen at deposition rates only slightly in excess of the critical load over five years has produced small, non-significant increases in shoot nitrogen content. However, there is clear evidence of a large positive effect on shoot growth, flowering, litter production and canopy density of Calluna. The observation of these responses at the application rates used in this study supports the current proposals for critical loads of nitrogen for lowland heaths.     

Ice core evidence for Antarctic sea ice decline since the 1950s

The instrumental record of Antarctic sea ice in recent decades does not reveal a clear signature of warming despite observational evidence from coastal Antarctica. Here we report a significant correlation (P < 0.002) between methanesulphonic acid (MSA) concentrations from a Law Dome ice core and 22 years of satellite-derived sea ice extent (SIE) for the 80 degrees E to 140 degrees E sector. Applying this instrumental calibration to longer term MSA data (1841 to 1995 A.D.) suggests that there has been a 20% decline in SIE since about 1950. The decline is not uniform, showing large cyclical variations, with periods of about 11 years, that confuse trend detection over the relatively short satellite era.     

Seeding and propagation of untransformed mouse mammary cells in the lung

The acquisition of metastatic ability by tumor cells is considered a late event in the evolution of malignant tumors. We report that untransformed mouse mammary cells that have been engineered to express the inducible oncogenic transgenes MYC and Kras(D12), or polyoma middle T, and introduced into the systemic circulation of a mouse can bypass transformation at the primary site and develop into metastatic pulmonary lesions upon immediate or delayed oncogene induction. Therefore, previously untransformed mammary cells may establish residence in the lung once they have entered the bloodstream and may assume malignant growth upon oncogene activation. Mammary cells lacking oncogenic transgenes displayed a similar capacity for long-term residence in the lungs but did not form ectopic tumors.