Biovailability of ivermectin administered orally to dogs

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C _max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C _max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C _max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.     

Characterization of the Difference of Starch Branching Enzyme Activities in Normal and Low-Amylopectin Maize during Kernel Development

In order to determine the reasons for the differences in structure between starch from a normal and a low-amylopectin maize variety the activities of all the enzymes in the committed pathway of starch synthesis were studied throughout kernel development. Levels of ADP glucose pyrophosphorylase and starch synthase activity were found to be broadly similar between the two varieties but the low-amylopectin starch (LAPS) maize variety showed dramatically reduced starch branching enzyme activity, with an almost total absence of the branching enzyme II isoform. Scanning electron microscopy showed a significant alteration in the morphology of the starch granules of the low-amylopectin maize. The results suggest that the increased amylose and the reduction of high molecular weight amylopectin in the LAPS starch results from the absence of the branching enzyme II isoform. This evidence supports the theory that the different branching enzyme isoforms contribute separately to the synthesis and final structure of amylopectin.     

Selectivity and mode of action of flamprop-isopropyl,isopropyl (±)-2-[N-(3-chloro-4-fluorophenyl)benzamido]propionate,in the control of Avena fatua in barley

The post-emergence herbicide isopropyl (±)-2-[N-(3-chloro-4-fluorophenyl)benzamido]propionate (flamprop-isopropyl) showed good activity against wild oat with selectivity in barley. The basis for activity and selectivity was similar to that previously established for benzoylprop-ethyl, and found to be dependent on its rate of degradation to the biologically active acid flamprop. Flamprop stunted the growth of the oat by inhibiting cell elongation and showed a relatively high rate of movement in the phloem, approximately five times that of benzoylprop. Selectivity of flamprop-isopropyl was dependent on its relative rate of hydrolysis and the subsequent detoxication of the acid to inactive conjugates. However, although the relative rate of de-esterification of flamprop-isopropyl was lower than that of benzoylprop-ethyl similar quantities of the parent ester gave comparable effects on oat. The inherent activity of flamprop is approximately twice that of benzoylprop. The effect of flamprop-isopropyl was best seen when the compound was applied during growth stages when the crop could offer the most effective competition to the wild oat. Throughout a range of growth stages the rate of hydrolysis of flamprop-isopropyl was higher in oat than in barley. The metabolism of the compound was not markedly affected when the plants were under stress.     

Selectivity and mode of action of ethyl (±)-2-(N-benzoyl-3,4-dichloroamiino)propionate in the control of Arena fatua in cereals

The activity of foliar applications of ethyl (±)-2-(N-benzoyl-3,4-dichloroanilino)—propionate(benzoylprop-ethyl)to oat was dependent upon its degradation to the biologically active acid (benzoylprop). The acid, unlike benzoylprop-ethyl, showed some movement via the phloem from the foliage to the stem where it inhibited stem elongation through an effect on cell expansion. The resulting stunted wild plants oat were unable to compete successfully with the cereal crop. Selectivity of the herbicide was dependent on its relative rate of de-esterification, and the subsequent detoxication of the acid to inactive conjugates. De-esterification was fastest in oat and slowest in wheat. The rate of detoxication in wheat prevented the accumulation of the acid to phytotoxic levels but in oat, although the rate of detoxication was higher, it failed to prevent the occurrence of phytotoxic levels of benzoylprop. In barley de-esterification was slower than in oat, and detoxication again failed to prevent some accumulation of the acid.     

Factors favouring the choice of flamprop-methyl,methyl (±)-2-[N-(3-chloro-4-fluorophenyl)benzamido] propionate for the control of avena species in wheat

The post-emergence herbicide, methyl (±)-2-[N-(3-chloro-4-fluorophenyl)benzamido]-propionate, flamprop-methyl, showed good activity against oat with selectivity in wheat. It was superior in performance to flamprop-isopropyl and benzoylprop-ethyl already being marketed for wild oat control. It gave even more effective control of seed set in the oat than did the other compounds, prevented tiller growth and as a result of its higher activity was less dependent on crop competition. Selectivity of flamprop-methyl, however, was similar to that previously reported for related compounds, i.e. it was dependent on its rate of degradation and the subsequent detoxication of the biologically active acid to inactive conjugates. The rate of degradation of flamprop-methyl is comparable to that of benzoylprop-ethyl but the more active acid produced accounts for the improved performance of the former. The corresponding ethyl ester showed the highest rate of degradation and although generally comparable in performance to the methyl ester there was a tendency for the inhibition on the oat to last for a shorter period. Performance of flamprop-methyl is influenced by environmental factors such as temperature or water stress. These factors had an effect during the first 2 weeks after compound application, reducing the translocation of the active metabolite to its site of action and having a small but detectable effect on the amount of acid produced.     

The basis of selectivity of 4-(2, 6-dichlorobenzyloxymethyl)-4-ethyl-2, 2-dimethyl-1, 3-dioxolan (WL 29, 226), a new pre-emergence herbicide for use in cereals

A series of pot experiments were undertaken to assess the selectivity of the pre-emergence herbicide 4-(2, 6-dichlorobenzyloxymethyl)-4-ethyl-2, 2, -dimethyl-1, 3-dioxolan (WL 29,226) against a number of annual weeds in wheat. When applied at dose rates of 0.5–2 kg/ha it gave good control of a number of annual monocotyledonous weeds, including Alopecurus myosuroides (blackgrass), without any adverse effects on the crop. WL 29,226 is relatively immobile in soil, remaining at the soil surface and thus favouring uptake via the emerging shoot. Since WL 29,226 is transported predominantly via the xylem, to reach its site of action in the regions of cell division, and hence to be effective, the compound has to penetrate the shoot either at or below the stem apex. The roots are inhibited only when these come into direct contact with the compound. Selectivity of the herbicide is dependent upon the relative anatomical positions of the stem apices of the weeds and the crop with respect to the soil surface. Mesocotyl elongation in many of the weed species was such that the meristematic tissue was raised to the soil surface and into contact with the compound during the emergence of the shoot. In contrast, the stem apex of wheat remained some distance below the soil surface until considerably later, by which time the leaf sheaths offered protection to the meristematic tissue from direct contact with the herbicide. Selectivity is further enhanced in the field as a result of both the depth of planting for wheat and the tendency of many annual weed species to germinate more readily when near the soil surface. Tolerance of the wheat is lost where it germinates in direct contact with the herbicide, due to the lack of any biochemical selectivity. Under field conditions WL 29,226 gives good control of many dicotyledonous species. In pot experiments, however, these exhibit some tolerance to the compound. Radio-tracer studies indicate that the tolerance shown by the shoots of these plants is due to limited transport of the herbicide from the shoot to its site of action at the apex. This suggests that control of broad-leaved weeds occurs predominantly through an inhibition of root growth. However, in species such as sugar-beet, soyabean and cotton a rapid rate of root elongation confers increased tolerance to the compound. Availability of WL 29,226 for uptake by young seedlings is favoured by soil moisture. Low temperatures further improve performance by reducing the rate of shoot emergence and hence prolonging contact with the compound at the most sensitive stage of growth. After emergence uptake of the compound via the shoot becomes a less efficient mode of entry.     

RADIOGRAPHIC BONE LOSS CORRELATIONS AND TECHNETIUM-99m-MDP BONE UPTAKE IN LIGATURE-INDUCED PERIODONTAL DISEASE IN THE BEAGLE

The goal of this study was to develop an animal model for the study of acute periodontal disease using silk ligatures in combination with a soft diet in eleven purebred beagle dogs. The silk ligatures were placed subgingivally on the mandible second and fourth premolar on one side of the mouth; the opposite side served as a control. Dogs were monitored during the 16–20 weeks of ligature placement, and for 48 weeks after ligature removal. Development of periodontal disease was evaluated by radiopharmaceutical uptake into bone, radiographic evidence of alveolar bone loss, attachment loss, gingival index and prostaglandin level. Bone loss occurred on the ligatured side during the ligature phase of the study. Radiopharmaceutical uptake was correlated with radiographic evidence of bone loss during the ligature phase. No significant bone loss occurred during the post-ligature phase. Progressive periodontal disease was induced during ligature placement. However, a chronic less aggressive form was not sustained by soft diet alone after ligature removal.     

Physical Properties and Gelation Behavior of a Low-Amylopectin Maize Starch and Other High-Amylose Maize Starches

This paper examines the effect of changes in fine structure due to hybrid breeding on gel formation and gel properties of high-amylose maize starches. Both small-strain oscillatory testing and uniaxial-compression testing ranked G′ and texture/strength, respectively, in the same order of HYLON® V starch <HYLON® VII starch <low-amylopectin starch (LAPS). The starch gels became more rigid and stronger as amylose content of the hybrids increased from HYLON V starch to LAPS. It was also noted in these studies that LAPS had the quickest onset of gelation and HYLON V starch had the slowest. The effect of preparation temperature on gel properties was also studied by cooking high-amylose starches at 250 °, 270 °, 290 °, 310 °, 330 °F in a mini-jet cooker with minimal steam. Temperature of jet cooking had an impact on the rate of sol-to-gel transformation of the starches, which in turn influenced the final gel properties. All three hybrids were strongest (highest fracture stress and strain values) when prepared at 270 °F. HYLON V had the narrowest cooking tolerance forming self-supporting gels from 270 ° to 310 °F, while LAPS was the most robust, forming acceptable gels throughout the range of temperatures tested.     

Molecular Structure of a Low-Amylopectin Starch and Other High-Amylose Maize Starches

The molecular structure of two commercially available high-amylose maize starches, HYLON® V starch and HYLON® VII starch, and of a newly developed low-amylopectin starch (LAPS) was examined. These high-amylose starches give three apparent fractions as determined by gel-permeation chromatography: a high-molecular weight (mol.wt) amylopectin fraction, a low-mol.wt amylose fraction, and an intermediate-mol.wt fraction which contains both linear and branched components. The low-mol.wt amylose fraction increases from 9·4% in HYLON V starch to 17·7% in HYLON VII starch and 26·5% in LAPS, whereas the high-mol.wt amylopectin fraction decreases from 31·1% in HYLON V starch to 13·8% in HYLON VII starch and 2·5% in LAPS. The percentage of linear components in HYLON V starch, HYLON VII starch, and LAPS are 42, 54, and 80%, respectively. High-amylose starches have a large proportion of long chains in their branched fractions compared to waxy-maize and normal-maize starch. Both HYLON VII starch and the LAPS give B plus V-type X-ray diffraction patterns, but the LAPS has even a higher gelatinization temperature, lower swelling power in hot water, and is more resistant to acid digestion. With the lack of amylopectin, amylose accounts for at least part of the double helical structure in the LAPS granules.     

Influence of the Cytokinin, 6-Benzylamino-9-(Tetrahydropyran-2-yl)-9H-Purine,on the Growth and Development of Some Ornamental Crops

Foliar sprays of the synthetic cytokin, 6-benzylamino-9-(tetrahydropyran-2-yl)-9H-purine (PBA), increased branching in carnation, chrysanthemum, poinsettia, petunia and fuchsia, which showed varying levels of tolerance. In no instance did PBA reduce plant height. Applications of PBA to carnation and chrysanthemum stimulated branching in both intact and pinched plants. Treatment a few days prior to pinching produced more uniform development of new laterals. Response to the compound was most favourable under optimum growing conditions. Under relatively poor light intensity the laterals exhibited a reluctance for continued elongation and showed marked chlorosis. Application of PBA to flower buds at an early stage of development increased both the diameter and the fresh weight of carnation flowers or chrysanthemum inflorescences when fully open. Response to the compound decreased with age of the bud at the time of treatment. In carnation the effects on size were accompanied by an increase in petal area together with an increase in the number of primary petals produced. Relatively high concentrations also induced the formation of secondary growing centres from which varying numbers of additional petals were produced. Relatively large numbers of these secondary centres within a flower resulted in an increased incidence of calyx splitting. These centres were not observed in chrysanthemum. The formation of secondary growing centres could also be induced by GA₃ and IAA. However, while these growth substances increased the diameter and fresh weight of carnation flowers, unlike cytokinins they had no apparent effect on the number of primary petals formed. Finally PBA was also observed to increase the longevity of cut flowers of carnation. This was particularly apparent at relatively low temperatures.