Efficacy of a 2 per cent moxidectin gel against gastrointestinal parasites of ponies

The efficacy of moxidectin was evaluated in young ponies naturally infected with gastrointestinal parasites. Eight animals were treated orally with moxidectin at 0.4 mg/kg bodyweight and eight received only the vehicle. They were all necropsied two weeks later. Faecal samples were examined daily for egg counts and larval cultures. Parasites were recovered from total faecal samples collected daily and from the gastrointestinal tracts at necropsy. Moxidectin reduced the strongyle egg counts by > 99 per cent from three days after treatment but some individuals remained positive for 10 days. The drug had little or no ovicidal activity. As evaluated in the critical-controlled test, moxidectin was 99 to 100 per cent effective (P < 0.05) against luminal stages of parascaris equorum, Strongylus vulgaris, Triodontophorus species, Craterostomum acuticaudatum, 19 cyathostome species and Oxyuris equi. Adult S edentatus were also completely removed. Its efficacy against third stage larvae of Gasterophilus intestinalis was 95 per cent (P < 0.05). Luminal nematode stages were removed within a few days, and bots continued to be eliminated for at least two weeks after treatment. No activity was observed against Anoplocephala perforliata. As evaluated in the controlled test, moxidectin was 100 per cent effective against Habronema muscae (P < 0.05) and had a 76 per cent but not significant efficacy against encysted small strongyle larvae.     

Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients

During the winter 1991-92, 42 reindeer hinds of the Kaamanen Experimental Reindeer Herd in Finnish Lapland, naturally infected with various parasites, were allocated to 3 groups. One group was an untreated control group and the other 2 groups received either moxidectin or ivermectin at a dose of 200 micrograms kg-1 subcutaneously. The efficacy of treatment was followed with monthly faecal examinations for nematode eggs and counting of warbles, Hypoderma tarandi larvae, and throat bots, Cephenemyia trompe larvae, from live animals in spring. The efficacy of moxidectin against warbles (92.8%) and throat bots (70.8%) did not match that of ivermectin, which was 100% against both species. Both moxidectin and ivermectin were effective against gastrointestinal trichostrongylid egg production over the December to May trial period indicating good efficacy against adult and inhibited trichostrongylids. Only non-significant differences were seen in weight development and calf birth weights between the groups. Because of its only moderate insecticidal efficacy, moxidectin cannot be recommended as an endectocide in reindeer.     

3-4-Methylenedioxymethamphetamine-induced acute changes in dopamine transporter function

The activity of the moxidectin as an 1% w/v injectable solution on first instar Hypoderma spp. has been evaluated in sixteen naturally infested young cattle. The animals were selected on the basis of their serological status and allocated to two groups of eight animals. At the end of November, one group was treated with moxidectin at a dose rate of 0.2 mg/kg via the subcutaneous route and the non treated control calves injected with the vehicle. The serological status was assessed 1, 2, 4, 8 and 12 weeks post treatment and the presence of Hypoderma lumps determined every two weeks from February to June. A 100% efficacy of the injectable formulation was demonstrated. A progressive fall of the antibody levels was observed in the treated calves for one month following treatment, suggesting a progressive action of the test compound and a limited risk of hypersensitivity.     

Differential pattern of c-fos mRNA in rat brain following central and systemic administration of interleukin-1-beta: implications for mechanism of action

The epidemiology of gastrointestinal nematodes was studied in a spring calving herd in northeast Mississippi. Pregnant, mixed breed beef cows (n = 15) were placed on a 10 ha fescue/bermuda grass pasture from January 1990-February 1992. In both years, calves were born from February-April and were weaned and removed from the pasture in mid-October. Fecal egg counts (EPG) and generic composition of nematodes in fecal cultures were determined monthly for cows and calves. Estimation of numbers of third-stage larvae on herbage also was determined monthly from March 1990-February 1992. Worm-free tracer calves (2-3 per month) were allowed to graze for 1 month periods and slaughtered for counting and identification of gastrointestinal nematodes. The mean monthly EPG of cows was consistently low (0.23-3.41); EPG of calves increased from spring through fall of both years. Five nematode genera were identified from fecal cultures of cows and calves. Ostertagia and Trichostrongylus spp. were the predominant nematodes in cows, while Ostertagia and Cooperia spp. were predominant in calves. Numbers of third-stage larvae on herbage declined from spring through summer and remained at low levels until late fall/winter, when numbers increased markedly. Eleven nematode species were identified from tracers, but O. ostertagi and Cooperia spp. predominated in most months. Seasonal changes in tracer worm counts coincided with similar changes in counts of third-stage larvae on herbage. Inhibition of O. ostertagi occurred in tracer calves during spring, but did not give rise to a marked increase in egg production in cows during fall.     

Efficacy of six anthelmintics against luminal stages of Baylisascaris procyonis in naturally infected raccoons (Procyon lotor)

The efficacy of six anthelmintics against natural infections of Baylisascaris procyonis in raccoons (n = 7 per drug) was determined in a series of critical tests. The drugs were given via moist cat food as a single dose or once daily for three consecutive days. Raccoons treated with pyrantel embonate (1 x 20 mg base kg-1 bodyweight (bwt.)), ivermectin (1 x 1 mg kg-1 bwt.), moxidectin (1 x 1 mg kg-1 bwt.), albendazole (3 x 50 mg kg-1 bwt.), fenbendazole (3 x 50 mg kg-1 bwt.) or flubendazole (3 x 22 mg kg-1 bwt.) expelled 1-198, 2-24, 2-14, 3-80, 2-70, or 2-35 B. procyonis stages, respectively, within the faeces. No roundworm was detected in any raccoon at post mortem examinations 7 days after the end of treatment. These results suggest that any of the six anthelmintics can be used at the dose rates tested in a deworming programme for captive raccoons.     

The effectiveness of a single treatment with doramectin or ivermectin in the control of gastrointestinal nematodes in grazing yearling stocker cattle

Four studies were conducted to a similar experimental design in the U.S. to evaluate the effectiveness of doramectin injectable administered to yearling stocker cattle in the control of gastrointestinal nematodiasis over the subsequent grazing period. Studies were conducted in Wisconsin (WI) and Arkansas (AR) during the summer season. The other two studies were conducted in Georgia (GA) and Mississippi (MS) during the winter/spring season. Doramectin was compared with both ivermectin injectable and ivermectin pour-on in the WI study, with ivermectin injectable alone in the GA study and with ivermectin pour-on alone in the other two studies. At each study site, an area of permanent pasture previously grazed by parasitized animals was subdivided by fencing into equal pasture units each with its own water supply. A treatment designation (non-medicated control, doramectin injectable, ivermectin injectable or ivermectin pour-on) was randomly assigned to each pasture unit. Weaned beef calves with confirmed gastrointestinal nematode infections were randomly allotted to a pasture unit and corresponding treatment group. Each treatment group consisted of three replicates of seven animals per pasture unit (total 21 animals) in the WI study, three replicates of four or six animals per pasture unit (total 16 animals) in the AR study, five replicates of six animals per pasture unit (total 30 animals) in the GA study and three replicates of 12 animals per pasture unit (total 36 animals) in the MS study. Treatments were 1% doramectin injectable solution, 1% ivermectin injectable solution, 0.5% ivermectin pour-on solution or non-medicated controls. The injectables were administered at a dose of 1 ml/50 kg body weight (200 micrograms doramectin or ivermectin/kg) by subcutaneous injection in the neck. Ivermectin pour-on solution was administered topically at a dose of 1 ml/10 kg body weight (500 micrograms ivermectin/kg). After receiving their prescribed treatment, animals were placed on their designated pasture unit where they remained for the entire grazing period (84-140 days). Fecal nematode egg counts and body weights were monitored at predetermined intervals throughout each study. Doramectin treatment reduced pretreatment egg counts by between 95 and 100% by 21 days post-treatment. Subsequent rises in egg output from exposure to infective pastures were delayed by two to four weeks resulting in substantial reductions in total egg deposition over the grazing period and, therefore, potential pasture recontamination. Doramectin treatment resulted in substantial average daily weight gain advantages (0.152-0.272 kg) over the grazing season compared to non-medicated controls. Advantages were statistically significant (P < 0.05) in three of the four studies. There were no significant differences (P > 0.05) in average daily gain between the doramectin and ivermectin injectable or ivermectin pour-on treated groups.     

Self-sustained pH oscillations in immobilized proteolytic enzyme systems

The efficacy of doramectin, a novel avermectin, was assessed against both naturally-acquired and experimentally-induced infections of gastrointestinal roundworms, lungworms, kidneyworms, lice and mites in studies conducted across North America and Europe. Twenty-two studies evaluated efficacy against fourth larval and adult stages of the following nematode species: Hyostrongylus rubidus, Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, Oesophagostomum quadrispinulatum, Trichuris suis, Metastrongylus spp. and Stephanurus dentatus. Efficacy was evaluated against the louse Haematopinus suis in six studies and against the mite Sarcoptes scabiei in four studies. A common study design was employed for each study type. In all studies, animals were allotted at random to a doramectin-treated or a saline-treated group. The doramectin-treated group received the drug at 300 micrograms kg-1 by intramuscular injection while the saline-treated group received saline by the same route. In the nematode studies, worm burdens were determined for each animal at slaughter 14-16 days after treatment. Efficacy against each nematode species/stage was assessed on the basis of percentage reduction in geometric mean worm burden in doramectin-treated animals compared with saline-treated controls. In louse and mite studies, counts were made immediately before treatment and then at weekly intervals for four weeks. Efficacy was based on a comparison of the level of infestation on the day of treatment with that on the last day of test. Data from individual studies were combined to derive a single estimate of efficacy against each of the parasite species represented in the study program. Efficacy of doramectin was 98% or greater against all nematode species except T. suis for which the efficacy was 87% and 79% against adult and fourth larval stage, respectively. Efficacy was 100% against both Haematopinus suis and Sarcoptes scabiei.     

Efficacy of an in-feed formulation of ivermectin against adult worms and somatic larvae of Strongyloides ransomi

The efficacy of an in-feed formulation (IVOMEC premix) containing 0.6% ivermectin was tested against Strongyloides ransomi in swine. The efficacy of ivermectin against patent infections of S. ransomi when given via the feed at 2 ppm for 7 days (Days 0-7) to provide 100 mcg ivermectin kg-1 body weight day-1 was evaluated in a study with 16 3-month-old male castrated piglets. Seven days prior to treatment each piglet was infected subcutaneously with 2500 infective larvae of S. ransomi. Fecal egg counts were carried out on Days -7, 0, 7 and 14, and worm counts on Day 14. Efficacy was 100% in all treated piglets. Two trials involving 40 pregnant gilts were carried out to evaluate the efficacy of ivermectin against the somatic larval stages of S. ransomi when given at a daily dose of 100 mcg kg-1 body weight for 7 days starting on Days 66, 78, 92 or 103 of pregnancy. The gilts were each experimentally infected with three subcutaneous injections of 250,000 infective larvae, with the last infection given between 12 and 30 days prior to commencement of treatment. Gilts were confirmed free of pre-existing intestinal stages of S. ransomi prior to ivermectin treatment. Fecal nematode egg counts were carried out in gilts/sows and piglets subsequently born. The Strongyloides larvae present in sow milk 1, 2 and 7 days post partum were counted. Fourteen days post natum, worm counts were performed in four randomly selected piglets for each litter. IVOMEC premix given to pregnant gilts prevented shedding of larvae in sow milk, egg output in feces and the establishment of S. ransomi in piglets.     

Effect of dietary chloride content on the elimination of bromide by dogs

The effect of dietary chloride content (0.2, 0.4 and 1.3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg-1) was evaluated in normal beagles. Increasing the dietary chloride content from 0.2 to 1.3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 +/- 22 days to 24 +/- 7 days. The mean area under the concentration curve (AUC) for dogs fed 1.3 per cent chloride was significantly smaller than the AUC for dogs fed 0.2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (Cmax) or on the time (Tmax) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg-1 of bromide were significantly lower in dogs fed 1.3 per cent chloride (310 +/- 150 mg litre-1) than in dogs fed 0.2 per cent chloride (1950 +/- 1140 mg litre-1). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1.3 per cent chloride (43 +/- 13 mg kg-1) were almost twice as high as the dose estimated for dogs fed 0.4 per cent chloride (22 +/- 3 mg kg-1) and nearly three times as high as the dose estimated for dogs fed 0.2 per cent chloride (15 +/- 4 mg kg-1). These differences were statistically significant (P = 0.002).     

Trends and international comparisons in infertility in circumpolar areas

A study was carried out at the International Livestock Research Institute (ILRI) Debre Berhan Research Station in Ethiopia from 1992 to 1995 to compare the peri-parturient rise (PPR) in faecal nematode egg counts (FEC) in ewes of two indigenous sheep breeds. A total of 1439 Menz and 1347 Horro ewes were single sire mated following oestrus synchronization to lamb in the wet and dry season. Three ewe treatment groups were constituted as mated/lactating/undrenched; mated/lactating/drenched; unmated/undrenched for three wet and three dry lambing seasons. All ewes grazed naturally contaminated pasture. Levels of faecal egg output were monitored at mating, 3 months after mating, 2 weeks before lambing, 4, 8 and 12 weeks post-lambing. A significant PPR in FEC occurred 2 weeks before lambing and peaked at 4 weeks post-parturition in ewes lambing just before the beginning of the dry season (October/November). There was no significant increase in FEC when lambing occurred before the onset of the long rainy season (May/June). The PPR in this study was associated with both lactation and seasonal availability of third-stage infective larvae on pasture. There was no consistent breed difference in FEC during the six sampling periods from mating to weaning. Faecal cultures and worm counts from both breeds confirmed the presence of Longistrongylus (Pseudomarshallagia) elongata, Trichostrongylus spp.and Haemonchus contortus. The role of the peri-parturient rise of FEC in ewes in gastrointestinal nematode transmission is discussed.     

Effect of prepartum bovine somatotropin in primigravid ewes on mammogenesis, milk production, and hormone concentrations

Twenty-five primigravid ewes were used to investigate the effect of bST, between 97 and 124 d of gestation, on mammogenesis and subsequent milk production. Five ewes (reference group) were slaughtered at 96 d of gestation, and the remaining ewes were injected daily with saline (control group: n = 10) or .1 mg/kg of BW of bST (bST group: n = 10). Following bST treatment, 5 control and 5 bST group ewes were slaughtered (slaughter group). The remaining ewes were slaughtered after lambing and being milked for 8 wk (production group). Weekly blood samples were obtained from both slaughter and production group ewes. Slaughter group ewes were also subjected to 8-h serial blood sampling at 98 d (period 1) and 123 d (period 2) of gestation. Milk production was 42% higher in ewes treated prepartum with bST than in those treated with saline. Results suggest that the increase in milk was due to an increase in mammary parenchymal cell number rather than to an increase in cellular activity. The high rate of [3H]thymidine incorporation into parenchymal tissue in reference group ewes suggests that the increase in parenchyma during the second trimester of gestation is due to cellular hyperplasia but that cellular hypertrophy may be more important during the last trimester. Plasma IGF-I concentrations were significantly higher during bST treatment and remained elevated between daily injections; the increase was greatest in period 2.     

Pharmacokinetics and metabolism of the new thromboxane A2 receptor antagonist ramatroban in animals. 1st communication: absorption, concentrations in plasma, metabolism, and excretion after single administration to rats and dogs

The absorption, concentrations in plasma, metabolism and excretion of ramatroban ((+)-(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid, CAS 116649-85-5, BAY u 3405) have been studied following a single intravenous, oral, or intraduodenal administration of 14C-labeled or nonlabeled compound to rats and dogs (dose range: 1-10 mg.kg-1). After intraduodenal administration of [14C]ramatroban, enteral absorption of radioactivity was rapid and almost complete both in bile duct-cannulated male rats (83%) and female dogs (95%). The oral bioavailability of ramatroban was complete in the dog but amounted to about 50% in the rat due to presystemic elimination. A marked food effect on the rate but not on the extent of absorption was observed in rats. The elimination of the parent compound from plasma occurred rapidly with total clearance of 1.2 l.h-1.kg-1 in male rats and 0.7 l.h-1.kg-1 in dogs. After oral administration to male rats AUC increased dose-proportionally between 1 and 10 mg.kg-1, whereas in Cmax an over-proportional increase was observed. Excretion of total radioactivity was fast and occurred predominantly via the biliary/fecal route in both species. The residues were low, 144 h after dosing less than 0.2% of the radioactivity remained in the body of rats. A considerable sex difference was found in rats following oral administration of ramatroban. In females a 3-fold higher AUC and a 1.7-fold longer half-life of unchanged compound, as well as 3-fold higher renal excretion of total radioactivity was observed. A marked species difference exists in the metabolism of ramatroban. In dogs the drug was almost exclusively metabolized via conjugation with glucuronic acid, whereas in rats oxidative phase I metabolism and glucuronidation were equally important. As a consequence enterohepatic circulation was much more pronounced in dogs (77%) than in rats (17% of the initial dose).     

Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice

Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.), migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34, 35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were measured in age matched non-infected mice by high performance liquid chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28, respectively) were significantly different (P < 0.01). Against pre-adult stages ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10 mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating and encysted larvae were less sensitive to both compounds and dose rates had to be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral stages, ABZ was significantly more effective than RBZ when both were given at 100 mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5% reduction against encysted larvae, respectively). In conclusion, RBZ was not more effective than ABZ against enteral and parenteral stages of Trichinella spiralis.     

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced pancreatic carcinoma: a University of Chicago phase II consortium study

BACKGROUND/OBJECTIVES: Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy. RESULTS: Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively. CONCLUSION: In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.     

Pharmacokinetics of the enantiomers of verapamil after intravenous and oral administration of racemic verapamil in a rat model

Verapamil is a chiral calcium channel blocking drug which is useful clinically as the racemate in treating hypertension and arrhythmia. The published pharmacokinetic data for verapamil enantiomers in the rat model are limited. Utilizing a stereospecific high-performance liquid chromatographic (HPLC) assay, the enantiomeric disposition of verapamil is reported after intravenous (1.0 mg kg-1) and oral (10 mg kg-1) administration of racemic verapamil to the rat model. After intravenous administration the systemic clearance of R-verapamil was significantly greater than that of S-verapamil; 34.9 +/- 7 against 23.7 +/- 3.7 mL min-1 kg-1 (mean +/- SD), respectively. After oral administration, the clearance of R-verapamil was significantly greater than that of S-verapamil, 889 +/- 294 against 351 +/- 109 mL min-1 kg-1, respectively. The apparent oral bioavailability of S-verapamil was greater than that of R-verapamil, 0.074 +/- 0.031 against 0.041 +/- 0.011, respectively. These data suggest that the disposition of verapamil in the rat is stereoselective; verapamil undergoes extensive stereoselective first-pass clearance after oral administration and the direction of stereoselectivity in plasma is opposite to that observed in the human.     

Efficacy of an ivermectin controlled-release capsule against nematode and arthropod endoparasites in sheep

Five controlled trials were conducted in Germany or in the United Kingdom, using 74 female sheep of merino or Dorset horn breeds, to evaluate the efficacy of an ivermectin controlled-release capsule against naturally acquired or induced infections of gastrointestinal nematodes, lungworms and nasal bot larvae and against incoming infections with gastrointestinal and pulmonary nematodes. Half of the animals were treated with one ivermectin controlled-release capsule that delivered ivermectin at the rate of 1.6 mg per day for 100 days while the other half remained untreated. Parasites were counted 21, 28, 35 or 56 days after administration of the capsule. The treatment was highly effective (> or = 99 per cent) against established parasites of the following species: Haemonchus contortus (adults and fourth-stage larvae), Ostertagia circumcincta, O pinnata, O trifurcata, Ostertagia species fourth-stage larvae, Trichostrongylus axei, T colubriformis, T vitrinus, Cooperia curticei, Nematodirus battus, N filicollis, Strongyloides papillosus, Chabertia ovina, Oesophagostomum venulosum, Trichuris ovis, Tr skrjabini, Dictyocaulus filaria, Protostrongylus rufescens and Oestrus ovis (larvae). The treatment prevented the establishment of the gastrointestinal nematodes H contortus, O circumcincta, T axei, T colubriformis, C curticei, N battus, N filicollis, Ch ovina, Oe vennulosum and the establishment of the lungworm D filaria by > 99 per cent compared with untreated controls (P < or = 0.01).     

Neuromuscular blockade with vecuronium and its reversal with edrophonium during total intravenous anesthesia, neuroleptanalgesia and sevoflurane anesthesia

The neuromuscular blocking effect of vecuronium and its reversibility ith edrophonium were studied under total intravenous anesthesia (TIVA) and compared with those under NLA or sevoflurane anesthesia (SA) in 30 surgical patients. The degree of neuromuscular blockade was evaluated by acceleration of thumb adduction in response to supramaximal stimulation of the ulnar nerve using Accelograph (Biometer). TIVA was induced with droperidol 0.25 mg.kg-1, fentanyl 2-4 micrograms.kg-1 and ketamine 2 mg.kg-1, and maintained with continuous infusion of ketamine 2 mg.kg-1.h-1 with 30-35% O2 in air. NLA was induced with droperidol 0.25 mg.kg-1 and fentanyl 5-10 micrograms.kg-1 and maintained with 66% nitrous oxide in oxygen. SA was induced with thiamylal 5 mg.kg-1 i.v. and maintained with 66% nitrous oxide in oxygen supplemented with sevoflurane (1 MAC). A single bolus intravenous injection of vecuronium 0.1 mg.kg-1 was used for paralysis and reversed with edrophonium 0.75 mg.kg-1 followed by atropine 0.015 mg.kg-1 when the TOF ratio returned to 25%. The times required from administration of vecuronium to completion of maximal block with TIVA, NLA and SA were 196.5 +/- 52.2 sec, 182.5 +/- 47.6 sec and 166.0 +/- 69.0 sec, respectively. There was no significant difference among them. The times from completion of maximal block to 25% recovery of the twitch height in TIVA and NLA were 39.5 +/- 11.0 min and 37.4 +/- 5.8 min without significant difference. Those values, however, were significantly shorter than 64.5 +/- 35.2 min of SA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of the genome of the gram-negative moderate halophiles Halomonas and Chromohalobacter by using pulsed-field gel electrophoresis

We investigated the relationship between maintenance bolus dose of vecuronium bromide (Vb) and the recovery time measured by TOF Guard in patients anesthetized with isoflurane (1.2-2.0%)-N2O-O2 (GOI group, n = 19) and epidural anesthesia (2% mepivacaine) plus isoflurane (0.5%)-N2O-O2 (EPI group, n = 14). In both groups, anesthesia was induced with propofol 2 mg.kg-1 and Vb 0.1 mg.kg-1 and ventilation was controlled to keep end tidal CO2 between 35-40 mmHg. When the muscle relaxation recovered to 25% of train-of four ratio (TOFR), doses of Vb 0.06, 0.04 or 0.02 mg.kg-1 were administered. Recovery time to TOFR 25% at each Vb dose (T 0.06, T 0.04 and T 0.02 respectively) was observed. T 0.02, T 0.04 and T 0.06 in GOI group were 36.7 +/- 3.2, 50.7 +/- 4.3 and 60.7 +/- 5.02 min (mean +/- SE), respectively and those in EPI group were 42.6 +/- 2.53, 52.2 +/- 2.51 and 59.9 +/- 3.22 min, respectively. There were no significant differences in the recovery time between these two groups. In both groups, although the recovery time to TOFR 25% was prolonged significantly in proportion to the increasing doses of Vb, the increase did not correlate with the dose of Vb. We suggest that frequent administration of Vb 0.02 mg.kg-1 decreases the total amount of Vb to keep TOFR within 25%.     

Depression in Parkinson''s disease. Pharmacological characteristics and treatment

An eight-year study was conducted to define the epidemiology of gastrointestinal nematode infection in Suffolk and Gulf Coast Native (Native) breeds of sheep, and to determine if the Native sheep is more resistant to infection. For the initial three years, each breed grazed separate pastures where anthelmintic treatments were administered to individual animals on a salvage basis. For the last five years, both breeds grazed concurrently; anthelmintic treatments were administered to individual animals on a salvage basis for the first three years, and to all animals, when treatment criteria were met, for the last two years. The fecal egg count (FEC) and blood packed cell volume (PCV) were monitored, and tracer lamb nematode burdens were determined. Overall, FEC for both breeds increased in the spring (periparturient rise) for most years and in the summer for all years. Under separate grazing conditions, Native ewes and lambs had consistently lower infection levels than Suffolk ewes and lambs. During the haemonchosis season (June-September) each year, Suffolk ewe and lamb PCV decreased, and Native ewe and lamb PCV remained relatively stable. The salvage treatment protocol resulted in 27 treatments for Suffolk and one for Native ewes; similarly for lambs, 13 for Suffolk and zero for Native. Tracer lambs grazed with their respective breed, and the FEC and mean total nematode burden corresponded with the pattern of infection for their respective breed. The predominant nematodes found in Suffolk and Native tracer lambs were Haemonchus contortus and Trichostrongylus spp., respectively. Under concurrent grazing conditions, the same seasonal repeatable pattern of infection was present and was exhibited by both breeds, with the Native ewes and lambs being consistently and significantly (p < or = 0.05) lower for FEC and higher for PCV. The salvage treatment protocol resulted in 57 and zero treatments for Suffolk and Native ewes, respectively; for lambs, 46 and 11. Tracer lamb nematode burdens again corresponded to their respective breed pattern of infection, with H. contortus and Trichostrongylus spp. being predominant in Suffolk and Native lambs, respectively. Data from all tracer lambs showed a relatively low level of hypobiosis (H. contortus only), and, although there was no consistent hypobiosis season, the tendency was for a higher level to occur in the fall. These results showed that the classic repeatable seasonal pattern of gastrointestinal nematode infection occurred in both breeds of sheep, and that Native sheep were more resistant to infection (specifically H. contortus) than Suffolk sheep.     

5-Hydroxytryptamine induces forestomach hypomotility in sheep through 5-HT4 receptors

The effects evoked by 5-hydroxytryptamine (5-HT; serotonin) on forestomach myoelectric activity were investigated in conscious sheep. Myoelectric signals were recorded with electrodes chronically implanted in the reticulum, rumen (dorsal sac) and omasal body, and were analysed by a computer-based method. The 5-HT receptors and the neuronal pathways involved in these actions were studied. The intravenous (i.v.) infusion of 5-HT (8 micrograms kg-1 min-1 for 5 min) evoked an inhibition of activity of the whole forestomach. Methiothepin, injected i.v. at 0.1 mg kg-1, inhibited rumen secondary contractions and omasum activity. However, forestomach activity remained unchanged after the administration of 0.2 mg kg-1 of ketanserin, ondansetron, tropisetron, GR-113808, phentolamine, propranolol, domperidone and naloxone. Atropine (0.2 mg kg-1), hexamethonium (2 mg kg-1) or haloperidol (0.1 mg kg-1) abolished rumen secondary cycles and inhibited omasum activity. In addition, atropine also suppressed primary cycles. GR-113808 blocked all 5-HT-induced effects. Furthermore, atropine or hexamethonium prevented the 5-HT-evoked inhibition of reticulorumen primary cycles. In contrast, the remaining antagonists did not alter the 5-HT-evoked forestomach hypomotility. In conclusion, 5-HT induces inhibition of forestomach myoelectric activity through 5-HT4 receptors, these actions being mediated by cholinergic neural pathways involving muscarinic and nicotinic receptors. However, adrenergic, dopaminergic or opiate pathways are not implicated.