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Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 145 records · Page 8Linked to original sources

Intraruminal controlled release of cyromazine for the prevention of Lucilia cuprina myiasis in sheep.

The efficacy of cyromazine, continuously released from intraruminal capsules at dose rates from 0.5 to 2 mg kg-1 d-1, was evaluated against implants of eggs and first instar larvae of Lucilia cuprina on Merino sheep. Estimates from the non-linear relationship between the success of implants and plasma concentrations showed that 95 per cent protection of sheep could be achieved at a mean release rate of 1.39 mg kg-1 d-1 cyromazine which gave rise to a mean plasma concentration of 0.26 mg litre-1. Present formulations allowed protection for about 90 days in a 40 kg sheep. The 'square wave' type of release profile provided negligible suboptimal dosing thus limiting the potential for selection of resistance. Systemic application of cyromazine provides control of covert and overt strike among sheep and could be used in ecologically based strategies for the control of L. cuprina populations.

Animals↗

Combined floxuridine and cisplatin in a fourteen day infusion. Phase I study.

Twenty patients received 28 courses of 5FUDR (floxuridine) admixed with Cisplatin (CDDP) and administered as a continuous infusion for 24 hours for 14 consecutive days. Pharmaceutical studies of the admixture of 5FU with CDDP and 5FUDR with CDDP demonstrated that only 5FUDR was compatible with CDDP and that the admixture was stable for 7 days. This Phase I study established the optimal dose rate for the individual components of the admixture and demonstrated that CDDP decreases the maximum tolerated dose rate for 5FUDR. The optimal dose rate for 5FUDR is 0.075 mg/Kg/d, and for CDDP the optimal dose rate is 7.5 mg/M2/d. Dose rate limiting toxicity is an enteritis which is radiographically similar to regional enteritis and is related to the 5FUDR. An ancillary finding was a significant decrease in serum magnesium levels in 11 of 13 monitored courses presumably related to the platinum.

Antineoplastic Combined Chemotherapy Protocols↗

Aspects of the biology of Ostertagia ostertagi in relation to the genesis of ostertagiasis.

Adaptations such as the capacity of free-living stages to survive environmental stress, inhibition and density-dependent effects on population size and fecundity show O. ostertagi to be a consummate parasite of cattle in temperate environments. Knowledge of these adaptations, within an animal management context, provides the key to understanding the occurrence of disease and a basis for control of parasite numbers. Substantial infections do arise from low egg contamination rates of pastures. Discontinuities in rates of infection are caused by poorly predicted seasonal events such as the effects on eggs of oxygen-deficient environments, fluctuating temperatures and the absence of sufficient moisture for migration of infective larvae from faeces to herbage. Time delays of several months between pasture contamination and availability of infection are therefore common. Ingestion of large numbers of larvae, over a short period early in the grazing season, gives rise to Type I disease or subclinical infections which decrease liveweight gains. In some ecotypes, environmentally induced inhibition leads to the accumulation of large populations of early 4th stage parasites within the host. These populations, under poorly defined conditions, can mature synchronously to produce severe diarrhoea, debility and even death in a proportion of mature cattle--the Type II disease.

Animals↗

Control of Ostertagia ostertagi infections in Australia.

The control of Ostertagia ostertagi infections in Australia is aimed specifically at young cattle in their first and second year of grazing after weaning. Mature breeding stock are not routinely treated. The recommended strategy is preventive, using an integrated approach of timed anthelmintic treatments in relation to the epidemiology of ostertagiasis in different environments. Best results are obtained when treatments, given at weaning and 6 months later, are combined with a move to 'safe' pastures which have not been grazed by cattle for the previous 6 months. Good results are also obtained in the winter rainfall regions when set-stocked cattle are treated before and during autumn to prevent contamination of pastures at this time. More complicated grazing management, involving the spelling of pastures during autumn and winter, combined with anthelmintic treatments, is needed in some summer rainfall regions where weather conditions are especially favourable for the development and survival of the free-living stages of O. ostertagi.

Age Factors↗

Composite electrode tips containing externally placed drug releasing collars.

We have developed a composite electrode tip based on a new concept whereby the electrode is combined with a polymeric collar containing dexamethasone sodium phosphate (DSP). The collar is positioned immediately adjacent to the electrode. Initial evaluation of this concept employed the Telectronics Laserpor electrode and a collar containing approximately 1.8 mg of DSP (LPD). Conventional Telectronics Laserpor (LP) electrodes were used as controls. Further evaluation was performed using a DSP (less than 0.5 mg) eluting collar and a new 4 mm2 mushroom shaped electrode with a high microsurface Pt/Ir coating (MD). Data for conventional Telectronics Laserdish (LD) electrodes were used for comparison. Unipolar ventricular leads were implanted transvenously in the right ventricular apex of sheep. Voltage thresholds, pacing (5 V, 0.5 ms) and sensing (50/100 mV RMS, 50 Hz) impedances were measured during the subchronic phase (less than 6 weeks) and in the case of LD and MD for 6 months. The steroid eluting electrodes were effective in eliminating (2 weeks vs. Impl., N.S.) the 2 week threshold peaking seen with the control leads (2 weeks vs. Impl., P less than 0.005). The small area MD electrode thresholds remained stable and low for up to 6 months (0.38 +/- 0.09 (10) c.f. 0.46 +/- 0.11(6); 14 and 180 days, respectively, N.S.). The composite electrode tips with steroid releasing collars thus show great potential for a substantial reduction in stimulation energy.

Animals↗

Effects of constant darkness and constant light on circadian organization and reproductive responses in the ram.

The relationship between circadian rhythms in the blood plasma concentrations of melatonin and rhythms in locomotor activity was studied in adult male sheep (Soay rams) exposed to 16-week periods of short days (8 hr of light and 16 hr of darkness; LD 8:16) or long days (LD 16:8) followed by 16-week periods of constant darkness (dim red light; DD) or constant light (LL). Under both LD 8:16 and LD 16:8, there was a clearly defined 24-hr rhythm in plasma concentrations of melatonin, with high levels throughout the dark phase. Periodogram analysis revealed a 24-hr rhythm in locomotor activity under LD 8:16 and LD 16:8. The main bouts of activity occurred during the light phase. A change from LD 8:16 to LD 16:8 resulted in a decrease in the duration of elevated melatonin secretion (melatonin peak) and an increase in the duration of activity corresponding to the changes in the ratio of light to darkness. In all rams, a significant circadian rhythm of activity persisted over the first 2 weeks following transfer from an entraining photoperiod to DD, with a mean period of 23.77 hr. However, the activity rhythms subsequently became disorganized, as did the 24-hr melatonin rhythms. The introduction of a 1-hr light pulse every 24 hr (LD 1:23) for 2 weeks after 8 weeks under DD reinduced a rhythm in both melatonin secretion and activity: the end of the 1-hr light period acted as the dusk signal, producing a normal temporal association of the two rhythms. Under LL, the 24-hr melatonin rhythms were disrupted, though several rams still showed periods of elevated melatonin secretion. Significant activity rhythms were either absent or a weak component occurred with a period of 24 hr. The introduction of a 1-hr dark period every 24 hr for 2 weeks after 8 weeks under LL (LD 23:1) failed to induce or entrain rhythms in either of the parameters. The occurrence of 24-hr activity rhythm in some rams under LL may indicate nonphotoperiodic entrainment signals in our experimental facility. Reproductive responses to the changes in photoperiod were also monitored. After pretreatment with LD 8:16, the rams were sexually active; exposure to LD 16:8, DD, or LL resulted in a decline in all measures of reproductive function. The decline was slower under DD than LD 16:8 or LL.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Specific antibodies and the selective inhibitor ICI 118233 demonstrate that the hormonally stimulated 'dense-vesicle' and peripheral-plasma-membrane cyclic AMP phosphodiesterases display distinct tissue distributions in the rat.

Polyclonal-antibody preparations DV1 and PM1, raised against purified preparations of rat liver insulin-stimulated 'dense-vesicle' and peripheral-plasma-membrane cyclic AMP phosphodiesterases, were used to analyse rat liver homogenates by Western-blotting techniques. The antibody DV1 identified only the 63 kDa native subunit of the 'dense-vesicle' enzyme, and the antibody PM1 only the 52 kDa subunit of the plasma-membrane enzyme. These antibodies also detected the subunits of these two enzymes in homogenates of kidney, heart and white adipose tissue from rat. Quantitative immunoblotting demonstrated that the amount of these enzymes (by wt.) varied in these different tissues, as did the expression of these two enzymes, relative to each other, by a factor of as much as 7-fold. The ratio of the dense-vesicle enzyme to the peripheral-plasma-membrane enzyme was lowest in liver and kidney and highest in heart and white adipose tissue. ICI 118233 was shown to inhibit selectively the 'dense-vesicle' cyclic AMP phosphodiesterase in liver. It did this in a competitive fashion, with a Ki value of 3.5 microM. Inhibition of tissue-homogenate cyclic AMP phosphodiesterase activity by ICI 118233 was used as an index of the contribution to activity by the 'dense-vesicle' enzyme. By this method, a tissue distribution of the 'dense-vesicle' enzyme was obtained which was similar to that found by using the immunoblotting technique. The differential expression of isoenzymes of cyclic AMP phosphodiesterase activity in various tissues might reflect a functional adaptation, and may provide the basis for the different physiological actions of compounds which act as selective inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗

Sequence variation of bovine elastin mRNA due to alternative splicing.

Poly A+ RNA, isolated from a single 210 day fetal bovine nuchal ligament, was used to synthesize cDNA by the RNase H method, using AMV reverse transcriptase for first strand synthesis and DNA polymerase I for the second strand. The cDNA was inserted into lambda gt10 using EcoRI linkers, and recombinant phage containing elastin sequences were identified by hybridization with a 1.3 kb sheep elastin cDNA clone, pcSELI (Yoon, K. et al., Biochem. Biophys. Res. Comm. 118: 261-265, 1984). Three clones containing the largest inserts of 2.9, 2.8, and 2.6 kb were selected for further study. The complete sequence analysis of the 3 clones was correlated with the sequence of 10.2 kb of the bovine elastin gene. The analyses: (i) showed that the cDNA encompassed the great majority of the translated sequence, (ii) ordered the tryptic peptides of porcine tropoelastin, (iii) determined new amino acid sequences not previously found in the porcine peptides and (iv) demonstrated that alternative splicing of the primary transcript leads to significant variation in the sequence of the translated portion of the mRNA.

Amino Acid Sequence↗

Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA.

Poly(A)+ RNA, isolated from a single 7-mo fetal human aorta, was used to synthesize cDNA by the RNase H method, and the cDNA was inserted into lambda gt10. Recombinant phage containing elastin sequences were identified by hybridization with cloned, exon-containing fragments of the human elastin gene. Three clones containing inserts of 3.3, 2.7, and 2.3 kilobases were selected for further analysis. Three overlapping clones containing 17.8 kilobases of the human elastin gene were also isolated from genomic libraries. Complete sequence analysis of the six clones demonstrated that: the cDNA encompassed the entire translated portion of the mRNA encoding 786 amino acids, including several unusual hydrophilic amino acid sequences not previously identified in porcine tropoelastin, exons encoding either hydrophobic or crosslinking domains in the protein alternated in the gene, and a great abundance of Alu repetitive sequences occurred throughout the introns. The data also indicated substantial alternative splicing of the mRNA. These results suggest the potential for significant variation in the precise molecular structure of the elastic fiber in the human population.

Amino Acid Sequence↗

Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration.

Serum from seven patients with paraneoplastic cerebellar degeneration contained anti-Purkinje cell antibodies. The samples were examined by immunoblotting to determine whether they recognized common antigens in isolated human Purkinje cell neurons. Two groups of antigens were detected by all seven sera with Mr 62/64 kd and 34 to 38 kd, both of which contributed to the Purkinje cell antigens detected immunohistochemically. These reactivities were absent from all controls tested. These antibodies may play a role in the pathogenesis of paraneoplastic cerebellar degeneration.

Antibodies↗

Controlled release technology for the control of helminths in ruminants.

Release rates from controlled release devices are determined by the device itself and thus are accurate, reproducible and predictable, whereas in general, prolonged or slow release systems are sensitive to environmental conditions. Diffusion and dissolution are the principal means of achieving controlled release. A diffusion system is specific for the active ingredient and release rate decreases proportionately to the square root of time because of a decreasing concentration gradient or an increasing diffusion path. In dissolution systems, the choice of matrix determines the rate of dissolution and release rates are linearly related to the area of dissolution which can be maintained constant. Consequently, this system has general application, a sharp cut-off point and can be used for more than one ingredient simulatenously. Potential disadvantages of controlled release technology centre on unacceptable tissue residues and parasite resistance to the chemicals used. Advantages include, the ability to programme the release of compounds to achieve specific effects for various periods, decreasing the frequency of dosage and increasing the choice of compounds for the control of parasitic infections. Sufficient epidemiological information should be available before controlled release technology is implemented. Existing anthelmintics and control strategies can be used to achieve an enhanced, but expected result, e.g., prolonged reduction in pasture contamination to protect both ewes and lambs. In future it should be possible to devise compounds and strategies appropriate to the unique features of controlled release technology, e.g., compounds which interrupt or inhibit the growth and development of parasites. Environmental impact should be low because of the specific effect and low dosage of the chemical used.

Animals↗

Resistance to benzimidazole anthelmintics in field strains of Ostertagia and Nematodirus in sheep.

Resistance to a range of benzimidazole anthelmintics was investigated in 2 strains of Ostertagia spp. One strain (SR80) had been exposed to fenbendazole, oxfendazole and thiabendazole, the other strain (KR79) only to thiabendazole. Both strains showed a high degree of resistance to albendazole, fenbendazole, oxfendazole and thiabendazole, which had efficiencies of 11-38% and 0-60% against all developmental stages of SR80 and KR79, respectively. There was no significant reduction in the KR79 worm count by thiabendazole at 132 mg kg-1 given either as a single dose or divided into 12 equal portions, one administered every 6h. Nematodirus spp were also found to be resistant to all benzimidazoles tested. Levamisole at 7 mg kg-1 and naphthalophos at 30 mg kg-1 had efficiences of 89 and 66%, respectively, against SR80 Ostertagia and 99 and 19% against Nematodirus, all but the last of these being significant reductions in worm burdens. The resistant SR80 Ostertagia occurred on a research station, but possibly originated from a property which 3 years earlier had supplied ewes to the station. The use of benzimidazole anthelmintics and subsequent grazing on worm-free pasture may have enhanced the level of resistance. A relationship was established between egg counts and adult worm counts 10 days post-treatment, which suggested that for Ostertagia the worm count could be predicted from the geometric mean egg count from about 10 animals. Thus, where an Ostertagia population is suspected of being resistant, an anthelmintic efficiency assay using pre- and post-treatment faecal egg counts should provide a satisfactory diagnostic procedure.

Animals↗