Anthelmintic action—A metabolic approach (a review)

The effects of anthelmintic drugs on intermediary metabolism of parasites can be examined using techniques developed for the investigation of metabolic regulation. Most attention has been paid to the pathways of respiratory metabolism in parasites, since maintenance of high energy levels is essential to an organism's survival. Respiratory metabolism is thus a prime target for anthelmintic attack. Parasites differ from their hosts in a number of pathways of respiratory metabolism and they produce incompletely-oxidised organic acids as end products.A variety of anthelmintic drugs have been shown to inhibit some enzymes of these pathways, including phosphoenolpyruvate carboxykinase, malate dehydrogenase, and the fumarate reductase, ‘succinoxidase’ and succinate decarboxylase systems. Energy synthesis in mitochondria from parasites is also inhibited by many anthelmintics: this target is a particularly important one since its properties differ significantly from those of the host. This process requires considerable study and it may not necessarily be valid to equate ‘uncoupling’ in mammalian tissues with that in parasite tissues. Changes in ATP levels affect flux through the respiratory pathways; a complete assessment of effects of anthelminstics on the respiratory pathways of parasites would include measurement of the uptake and utilization of carbon sources (e.g., glucose and glycogen), of metabolic intermediates, including adenine nucleotides, and of excreted end products. Sites of change can then be identified and studied in greater detail.Comparison of the effect of mebendazole in vivo and in vitro on unrelated species, Moniezia expansa and Fasciola hepatica adults, sheds some light on the mechanism of its anthelmintic effects. This drug elicits similar changes in proportions and totals of adenine nucleotides in the two species, but it differs in the rapidly of its effect, its effect on glucose uptake and glycogen depletion, and in changes in respiratory end product. Consequently mebendazole may not act in the same way against these two species. It also affects a number of other systems in other parasites: the suggestion of a single ‘mode of action’ may be inappropriate for this compound.Respiratory metabolism is not the only system affected by anthelmintics: other parasite systems are also attacked, but the final effect of lethal anthelmintic is observed as changes in the respiratory metabolic pathways. Some anthelmintics, for example, levamisole, affect the respiratory pathway directly, but also affect other systems (the nervous system in the case of levamisole) and may be effective in vitro but not in vivo. In these cases it is necessary to distinguish between effects that may be subordinate to a primary effect, and to take host and permeability factors into account.     

Hematuria associated with cystic hematomas in three neonatal foals

Cystic hematomas were diagnosed in 3 neonatal foals. In all 3 foals, cystic hematomas resulted from umbilical trauma or thrombocytopenia. Findings in these foals suggest that cystic hematoma should be included in the differential diagnosis of hematuria in neonatal foals. Management of cystic hematomas includes both medical and surgical options.     

Evaluation of a lithium dilution cardiac output technique as a method for measurement of cardiac output in anesthetized cats

OBJECTIVE: To evaluate the use of a lithium dilution cardiac output (LiDCO) technique for measurement of CO and determine the agreement between LiDCO and thermodilution CO (TDCO) values in anesthetized cats. ANIMALS: 6 mature cats. PROCEDURE: Cardiac output in isoflurane-anesthetized cats was measured via each technique. To induce different rates of CO in each cat, anesthesia was maintained at > 1.5X end-tidal minimum alveolar concentration (MAC) of isoflurane and at 1.3X end-tidal isoflurane MAC with or without administration of dobutamine (1 to 3 microg/kg/min, i.v.). At least 2 comparisons between LiDCO and TDCO values were made at each CO rate. The TDCO indicator was 1.5 mL of 5% dextrose at room temperature; with the LiDCO technique, each cat received 0.005 mmol of lithium/kg (concentration, 0.015 mmol/mL). Serum lithium concentrations were measured prior to the first and following the last CO determination. RESULTS: 35 of 47 recorded comparisons were analyzed; via linear regression analysis (LiDCO vs TDCO values), the coefficient of determination was 0.91. The mean bias (TDCO-LiDCO) was -4 mL/kg/min (limits of agreement, -35.8 to + 27.2 mL/kg/min). The concordance coefficient was 0.94. After the last CO determination, serum lithium concentration was < 0.1 mmol/L in each cat. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a strong relationship and good agreement between LiDCO and TDCO values; the LiDCO method appears to be a practical, relatively noninvasive method for measurement of CO in anesthetized cats.     

Sampling to characterize landscape pattern

Current reseach suggests that metrics of landscape pattern may reflect ecological processes operating at different scales and may provide an appropriate indicator for monitoring regional ecological changes. This paper examines the extent to which a 1/16 areal subset of the landscape using equally spaced 40-km² hexagons can characterize the spatial extent of land cover types and landscape pattern (number of types of edges, patch shape complexity, dominance, and contagion). For 200-m resolution data the hexagon subset gives a reasonable estimate of overall landscape cover but may not be adequate for monitoring uncommon land cover types such as wetlands. For agriculture and forest, their proportion of the full landscape units is only outside the 95% confidence interval of the hexagon estimate 4–8% of the time, whereas the proportions for wetland and barren areas are outside the confidence interval 11–34% of the time. The hexagon subset also does not appear to be adequate as the sole basis for monitoring landscape pattern. The values for contagion, dominance, and shape complexity calculated on the full landscape units are outside the 95% confidence interval of the hexagon estimate 27–76% of the time. Other statistical analyses include regressions between full landscape and hexagon subsets, mean differences and standard errors along with tests on number of positive and negative values, and percent relative error of hexagon estimates.Although the research described in this article has been funded in part by the U.S. Environmental Protection Agency, under Interagency Agreement DW89934921-01-0 with the U.S. Department of Energy under Contract DE-AC05-84OR21400 with Martin Marietta Energy Systems, Inc., it has not been subjected to Agency review. Therefore, it does not necessarily reflect the views of the Agency. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.Research supported by the Landscape Characterization Project, Environmental Monitoring and Assessment Program, U.S. Environmental Protection Agency, under Interagency Agreement DW89934921-01-0 with the U.S. Department of Energy under Contract DE-AC05-84OR21400 with Martin Marietta Energy Systems, Inc., Environmental Sciences Division Publication No. 4090.     

Synergistic action of mebendazole and levamisole in the treatment of a benzimidazole-resistant Haemonchus contortus in sheep

One-year old worm free, merino wethers, were each infected with 5000 H. contortus larvae of a strain resistant to mebendazole at a rate of 52 mg/kg body weight of sheep. After 21 days, they were assigned to two trials. The preliminary trial showed that mebendazole and levamisole acted synergistically on the H. contortus infection. In the second trial, sheep were treated with 0.35 mg/kg levamisole (one seventh the minimum effective dose against susceptible worms) or 40 mg/kg mebendazole (40 times the minimum effective dose against susceptible worms). In each case the anthelmintics did not reduce worm burdens, although mebendazole depressed egg production. However, when mebendazole and levamisole, at the above dose rates, were administered simultaneously, total worm counts in sheep were reduced by almost 60%. Similar results were obtained when the levamisole was administered 8 h or 14 h after mebendazole treatment. The implications of these observations for the treatment of benzimidazole-resistant haemonchiasis in sheep are discussed.     

Role of the tendons of the biceps brachii and infraspinatus muscles and the medial glenohumeral ligament in the maintenance of passive shoulder joint stability in dogs

OBJECTIVE: To objectively evaluate the effect of transecting the tendon of the biceps brachii muscle (BBT), tendon of the infraspinatus muscle (IFS), or medial glenohumeral ligament (MGHL) on shoulder joint stability in canine cadavers. SAMPLE POPULATION: 81 forelimbs from mature dogs. PROCEDURE: Cadaver forelimbs were placed in a testing frame and axially preloaded with 4 kg of weight. Shoulder joint stability was tested in neutral joint position, flexion, and extension before and after transection of the BBT (n = 37), IFS (37), or MGHL (7). Humeral translation relative to the glenoid was induced by applying a 3-kg load in each of 3 directions (cranial, lateral, and medial) and quantitatively measured by use of an electromagnetic motion tracking system. Peak translational data were compared in each joint position before and after transection of the BBT, IFS, or MGHL. RESULTS: When tested in neutral position, the cranial, lateral, and medial translation of the humerus was significantly increased after BBT transection. In the flexed position, translation of the humerus in the cranial and lateral directions was significantly increased after BBT transection. In the extended position, the medial translation of the humerus was significantly increased after BBT transection. Complete medial luxation of all humeral heads occurred following transection of the MGHL. CONCLUSIONS AND CLINICAL RELEVANCE: The BBT contributes to passive shoulder joint stability in dogs, particularly in the neutral and flexed positions. It also provides medial stability during shoulder joint extension. Complete luxation of the joint occurs when the MGHL is transected.     

Isolation and characterization of an adventitious avian leukosis virus isolated from commercial Marek's disease vaccines

Commercial Marek's disease (MD) vaccines produced by two manufacturers were tested for possible contamination with avian leukosis virus (ALV). Samples of MD vaccines manufactured by two companies (A and B) were received from a breeder company; samples were also received directly from vaccine company B. Using virus isolation tests, samples initially tested positive for subgroup E (endogenous) ALV. However, upon repassage, the vaccines also tested positive for exogenous ALV. The isolated exogenous ALV proved to be a subgroup A virus, as determined by flow cytometry using polyclonal chicken antibodies specific for various subgroups of ALV, and by DNA sequencing of the envelope glygoprotein (gp85). The exogenous ALV isolated from MD vaccines was inoculated in chickens from ADOL lines 15I(5) x 7(1) and 0 to determine its pathogenicity and compare it with that of Rous-associated-virus-1 (RAV-1), the prototype strain of ALV-A. Each chicken from each line was inoculated with approximately 10,000 infectious units of RAV-1 or the ALV-A isolated from vaccines termed B-39 virus at 7th day of embryonation. At hatch, and at 4, 8, and 16 wk of age, chickens were tested for viremia and cloacal shedding; chickens were also observed for ALV-induced tumors within 16 wk of age. Viremia and cloacal shedding results suggest that chickens from both lines were susceptible to infection with either virus. Within 16 wk of age, the proportion of ALV tumors induced by strain B-39 in line 0 and line 15I5 x 7(1) chickens was 0% and 12%, respectively, compared with 62% and 67% in chickens inoculated with RAV-1. The data indicate that commercial MD vaccines produced by two manufacturers were contaminated with endogenous subgroup E and an exogenous subgroup A ALV. Further, data from biological characterization suggest that the ALV-A isolated from commercial MD vaccines is of low oncogenicity, compared with that of RAV-1. GenBank accession numbers: The gp85 gene sequences of ALV isolated from commercial Marek's disease vaccines have been deposited in GenBank and assigned the following accession numbers: A46 subgroup A, DQ412726 ; B53 subgroup A, DQ412727; A46 subgroup E, DQ412728; B53 subgroup E, DQ412729.     

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery

OBJECTIVE: To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. ANIMALS: 8 healthy adult horses. PROCEDURE: Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. RESULTS: Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.