Infection of sheep with adult and larval Ostertagia circumcincta: abomasal morphology

The infection of parasite-naive sheep with approximately 15,000 adult Ostertagia circumcincta via abomasal cannulae resulted in marked changes in the structure and function of the abomasum. The functional changes, which have been characterised previously, included elevated abomasal pH and increased serum concentrations of pepsinogen and gastrin. Eight days after the transplant of adult worms, the abomasa of recipient animals were significantly heavier than those of controls (P < 0.001), the thickness of the fundic mucosa was greater (P < 0.01), there were fewer parietal cells (P < 0.01) and increases in the numbers of mitotic figures and mucus-producing cells. Mucous cell hyperplasia was also evident in the fundic mucosae of sheep receiving a trickle infection of infective, third-stage O. circumcincta larvae and was prominent within nodules associated with larval development. In non-nodular mucosa, there was hyperplasia of mucous cells and changes in the distribution of parietal cells. Decreases in the number of parietal cells at the gland base were offset by increases at a mid-gland level, probably due to chronic hypergastrinaemia, so that, overall, total parietal cell number was unaffected. Mucous cell hyperplasia and the diminution of parietal cell number are seen in a diverse range of disease states and may be mediated by host growth factors such as Transforming growth factor-alpha. Alternatively, the cellular and/or the secretory changes in response to the presence of adult worms are mediated by chemicals that are cytotoxic/inhibitory for parietal cells, and released by the parasites themselves.     

Anti-larval antibodies in the serum and abomasal mucus of sheep hyperinfected with Haemonchus contortus

A radioimmunoassay technique was used to follow the anti-larval antibody response in the serum of sheep subjected to repeated dosing with Haemonchus contortus. The response was found to develop slowly and seemed to decline as soon as the sheep stopped receiving larvae. No immunological memory was observed after the sheep were challenged with 4000 larvae nine weeks after daily dosing was stopped. Examination of abomasal mucus collected from the sheep at slaughter revealed the presence of IgA and IgG antibodies. It is suggested that most of this mucus IgG was derived from blood whereas the IgA was locally produced.     

Normal abomasal electromyography and emptying in sheep and the effects of intraabomasal volatile fatty acid infusion

Electromyographic activity and emptying of the abomasum were studied in 3 sheep. Pacesetter potentials (PP), with a frequency of 6.06 +/- 0.05 (X +/- SEM) cycles/minute and propagated distally with an increased conduction velocity approaching the pylorus, were recorded from the distal 11 cm of the antrum. Spike burst and fused action potentials (AP) were superimposed on a variable percentage of PP. The aborad propagation of both types of AP was associated with abomasal emptying at the net rate of 12.61 +/- 1.38 (X +/- SEM) ml/minute. Intraabomasal infusion of 50 ml of a 300 mM solution of either acetic, propionic, or butyric acid was associated with a marked decrease in abomasal AP activity and in the emptying rate. Butyric acid was most effective, followed by propionic and acetic acids. The importance of the results in relation to the pathogenesis of left displaced abomasum (LDA) in dairy cows was noted.     

Bioavailability comparison between albendazole and albendazole sulphoxide in rats and man

Many restorative materials are claimed by their manufacturers to match the Vita shade guide. To verify this claim, 40 dental personnel were asked to color match five different restorative materials to their respective Vita shade tabs according to a 5-point scale (1 = very poor color match; 5 = excellent color match). Three shades were chosen for each restorative material (a mid-Value shade as well as the highest Value shade and the lowest Value shade present in each system). Pooled scores indicated that the resin composite materials had significantly better overall shade match than did the other materials evaluated and that one resin-modified glass-ionomer cement had significantly better shade match than did the "compomer" and another resin-modified glass-ionomer cement. Only 11% of the scores for all material and shade combinations were given a good or excellent rating (score greater than 3). Shade match to the Vita shade guide was not material dependent but tended to differ among the different Value shades evaluated.     

Combined albendazole and praziquantel versus albendazole alone in the treatment of hydatid disease

BACKGROUND/AIMS: This study was conducted to evaluate the effect of different regimens of medical treatment in hydatid disease at the Armed Forces Hospital, Riyadh. METHODOLOGY: Between April 1985 and August 1990 albendazole was used alone in the treatment of 22 patients with hydatid disease, mainly of the liver. Since September 1990, we have used a combination treatment of albendazole and praziquantel in 19 patients. RESULTS: For those patients treated only with albendazole, 8 patients (36.4%) showed a complete disappearance of the cyst, in 4 of which the treatment period ranged between 6 months to 2 years. The other 4 patients had ruptured liver cyst into biliary tree and had endoscopic treatment with complete recovery over a short period. For those patients treated with albendazole and praziquantel the following results were found. During a follow-up period of 2 months to 3 years and a treatment period of only 2-6 months there was complete disappearance of the hydatid cyst in 9 patients (47.4%) and over 50% reduction of the hydatid cyst in 5 patients (36.84%). CONCLUSION: Combination treatment with albendazole and praziquantel for hydatid disease is more effective than albendazole alone.     

IgE antibody during infection with the ovine abomasal nematode, Teladorsagia circumcincta: primary and secondary responses in serum and gastric lymph of sheep

A monoclonal antibody to ovine IgE was employed in an ELISA to investigate the IgE antibody responses in serum and gastric lymph to a primary infection of Teladorsagia circumcincta, and following challenge in previously infected sheep. During a primary response, IgE antibody to antigens derived from the infective third stage (L3) and adult (L5) worms were negligible, with low levels of IgE antibody detected in serum and lymph. In contrast, there was a pronounced IgE antibody response in 2/4 sheep to L3 antigens during 2-8 days after challenge of previously infected animals but low levels of IgE antibody to L5 antigens. This response was confirmed in a second but similar experiment, where relatively high levels of IgE antibody was detected to antigens from L3. Antibody levels were higher in lymph than in serum from the same animals, and Western blots of L3 antigen following SDS-PAGE under reducing conditions revealed several bands of MW26-96KD which reacted with the IgE antibody from gastric lymph. Immunohistochemical staining indicated that these IgE antibodies may be reacting with allergens associated with the surface cuticle of the worms.     

Aetiology and Pathogenesis of abomasal displacement in dairy cattle

A clinical chemical survey is given of the complex of factors which are involved during development of clinically manifest hypotony or atony of the abomasum prior to abomasal displacemnts. The importance of a change in the acid-base balance of the animals is especially stressed as a predisposing factor. The further pathogenesis of abomasal displacement is supposed to follow different ways, according to the feeding and to prevailing periods of indigestion.     

Occurrence of abomasal displacement in cattle in Hesse

In veterinary practices in Hesse cattle diagnosed with abomasal displacement increased from 0.18% in 1980 to 0.6% in 1992. In this period the percentage of left abomasal displacement (L) (75-83%), right abomasal displacement (R-) (13-16%), and abomasal volvulus (R+) (4-8%) remained constant. In the Medical and Forensic Veterinary Clinic of the University of Giessen (MGV 2) cattle diagnosed with abomasal displacement increased from 2.1% in 1970 to 25.6% in 1992. In this period the percentage of L, R- and R+ was 71, 15 and 13% respectively. The percentage of L had decreased in this period. In 1988 and 1992 the percentage of the Deutsche Schwarzbunte (DSB) breed was 51 and 52% in the Hessian cattle population and with that lower than the percentage of cattle diagnosed with abomasal displacement in the MGV 2, where the percentage of DSB was 80% in 1988 and 79% in 1992. In the period between 1970 and 1992 the percentage of DSB in all cattle referred to the MGV 2 was 51% and with that lower than in cattle diagnosed with abomasal displacement, where it was 80%. The findings indicate, that in Hesse the DSB breed is predisposed to abomasal displacement.     

Kinetic disposition of an emulsifiable concentrate formulation of deltamethrin applied to sheep in a plunge-dip and its effect on lice

An emulsifiable concentrate formulation of the synthetic pyrethroid insecticide deltamethrin was applied in a plunge dip, 3 weeks after shearing, to a group of 5 Merino sheep infested with sheep body lice, Bovicola ovis. Deltamethrin concentrations on the wool were measured at regular intervals between 1 and 98 days after treatment and were not significantly different (P > 0.05) between sites on the dorsal mid-line, upper or lower flank. Levels in the tip of the fleece were significantly greater than those in the base, indicating that there was little movement of deltamethrin down the staple as the wool grew. Most lice were killed after 20 h of exposure in vitro to wool samples collected between 1 and 28 days after treatment. However, many lice survived in samples containing a similar concentration of deltamethrin, but collected between 35 and 98 days after treatment. Numbers of lice surviving increased with the sampling time after treatment, suggesting that the bioavailability of the deltamethrin changed as the insecticide aged in the fleece. Some transfer of deltamethrin occurred from treated to untreated sheep. The levels of deltamethrin were higher in sheep placed in contact with the treated group at 14 days after treatment than in those which were in contact from 43 days after treatment.     

Liposomes disposition in vivo. V. Liposome stability in plasma and implications for drug carrier function

The kinetics of [14C]sucrose release from multilamellar liposomes of fixed diameter (approx. 0.23 micron) incubated in human plasma (serum and blood) were quantified. Composition was various ratios of phosphatidylcholine, phosphatidic acid and cholesterol with alpha-tocopherol included as antioxidant. Considerable intra-individual variability was noted for liposome stability in blood and its derived fluids, yet reproducible results were obtained for pooled samples. The destabilizing effects of plasma decreased with increasing lipid concentrations. Results of fitting a kinetic model to the data showed that four of five model parameters were linearly related to liposome cholesterol content. Liposomes depleted plasma of its destabilizing factors, and when pre-incubated with plasma were partially stabilized to the effects of a subsequent plasma addition. Plasma caused a rapid rise in liposome membrane permeability which then declined non-linearly, presumably because of a rearrangement of membrane lipids and adsorbed proteins to form their most stable configuration. The therapeutic availability of drugs administered encapsulated in liposomes, which can be governed by the kinetics of their in vivo extracellular release, may be directly proportional to--and predictable from--the time-course and extent of release in plasma. The kinetic model was used in conjunction with simple pharmacokinetic assumptions to show that the effectiveness of a liposome drug carrier cannot be predicted based simply on its plasma stability; more stable liposomes may not be more effective drug carriers. Interestingly, plasma-induced solute release from liposomes serendipitously mimics an important facet of ideal carrier behavior.     

Effects of incremental cortisol and adrenalectomy on plasma corticosteroid binding capacity in fetal sheep

The effects of incremental cortisol infusion or fetal adrenalectomy on plasma corticosteroid-binding capacity (CBC) were examined in sheep fetuses during late gestation (term approximately 150 days). Cortisol, infused from day 120 at 1.5 mg/day for the first 3 days, 2.5 mg/day for the next 5 days, and 3.5 mg/day for the final 2 days, stimulated a significant rise in plasma CBC and immunoreactive corticosteroid binding globulin (CBG). There was a significant positive correlation between individual values for total plasma cortisol concentrations and CBC values. In contrast, fetal adrenalectomy at day 115 prevented the rise in plasma CBC found in intact fetuses at term. These experiments show that exogenous cortisol, given in a manner that mimics the prepartum rise in fetal plasma cortisol, stimulates CBG biosynthesis, whereas abolition of the cortisol rise prevents the increase in CBG. The study provides strong support for the proposal that the prepartum increase in CBG biosynthesis in fetal sheep occurs in response to the progressive rise in adrenal cortisol output by the fetus towards term.     

Relationships between individual differences in salt appetite of sheep and their plasma electrolyte status

A pasture was prepared so that an equilibrium of fresh and ageing eggs of Taenia hydatigena was present. This was done by placing dogs with patent infections on it for six months. Five months after their introduction, groups of lambs were grazed there for two, four, eight, 16 or 32 days. The dogs were then removed. Three and six months later, further groups of sheep were grazed there for a similar period. The infection pressures and the indices of clustering of the eggs were calculated by an examination of the lambs for cysts at autopsy. When the dogs were present, the daily rate of infection was about 60 per cent of the flock. This was reduced to 6.5 per cent then to 3.5 per cent within three and six months respectively after their removal. Very high cyst counts were obtained in some animals and the indices of dispersion diverged from a Poisson model during the period when the lambs were maintained on the pasture in the presence of the dogs. There was a trend for a reduction in the mean cyst counts and the index of dispersion tended to conform more closely to a Poisson model the longer the dogs were excluded. There was also a corresponding reduction in the survival rate of the cysts. It was suggested that an asymptote of less than 100 per cent in the prevalence rate may be accounted for by the acquisition of resistance without the persistence of infection and this was induced in some animals by the initial ingestion of ageing organisms which gradually formed the predominant type after the removal of the dogs from the pasture.     

Whole-body autoradiographic disposition and plasma pharmacokinetics of 5,10-dideazatetrahydrofolic acid in mice fed folic acid-deficient or regular diets

The effect of folic acid depletion on the tissue distribution and plasma pharmacokinetics of the oncolytic agent 5,10-dideazatetrahydrofolic acid (DDATHF) was evaluated in mice fed either folic acid-deficient or regular diets. Mice were maintained on diets for 2 weeks prior to receiving a single i.v. 30 mg/kg dose of [14C]DDATHF (tissue distribution) or DDATHF (plasma pharmacokinetics). Whole-body autoradiographic evaluation and plasma analysis for DDATHF were conducted in mice at 5 min and 6, 24, 48, 96, 120, and 168 h postdose. Radiocarbon associated with [14C]DDATHF was readily distributed to all tissues in both diet groups at the early time points and was rapidly cleared from most tissues at 24 h postdose. At the later time points, substantial amounts of radioactivity remained in liver from mice fed either diet. However, levels of radiocarbon in liver from mice fed the folic acid-deficient diet were approximately 2.5-4.2-fold the radiocarbon levels in liver from mice fed the regular diet. Similarly, plasma pharmacokinetics indicated that mice fed the folic acid-deficient diet had sustained plasma concentrations of DDATHF compared to plasma concentrations in mice fed the regular diet. These data indicated that a deficiency in dietary folic acid in mice caused increased hepatic retention of radioactivity and sustained plasma concentrations of DDATHF which are probably responsible for the observed toxicity of DDATHF in mice.     

Quantitation in plasma and urine of acebutolol and a major metabolite with preliminary observations on their disposition kinetics in man

An acetyl-homologue-metabolite, present in concentrations of up to ten times those of the unchanged drug, in the plasma of patients receiving oral doses of acebutolol, is reported. Combined gas chromatography--mass spectrometry has been utilized to determine the structure of the acetyl-metabolite. This acetyl-metabolite has been measured as acebutolol by previously published non-specific methods for the determination of acebutolol in biological fluids. A specific and sensitive gas chromatographic method is described for the separate quantitation of acebutolol and its acetyl-metabolite in plasma and urine. Using our method, preliminary data on the disposition kinetics of acebutolol are presented. The difficulties in interpreting previously published pharmacokinetic data for acebutolol, based on a non-specific method of analysis, are emphasized.     

Pharmacokinetics and disposition of triptonide in rats

Triptonide, isolated from Tripterygium wilfordii Hook., was found to show significant antiinflammatory, immunosuppression and antitumor activities. A RP-HPLC method was applied to determine the plasma concentration of triptonide at different times in rats. Concentration-time curves after i.v., 0.7, 1.4 and 2.8 mg.kg-1 of triptonide were fitted to a two-compartment open model with T1/2 alpha of 0.167-0.195 h and T1/2 beta of 4.95-6.49 h. The area under curves (AUCs) were linearly related to the dosages (gamma = 0.9894). Systematic clearances (CLs) were independent of dosages. Mean residence time (MRT) of the three doses was 3.26-5.14 h by noncompartmental (the statistical moment method) analyses. The tissue distribution of triptonide in rats appeared to be wide throughout the body. The triptonide levels were high in the lung and liver, moderate in the heart, kidney, spleen and muscle and low in the testis, intestine and brain. Data of the urine and bile excretion indicated that only a small percent of unchanged triptonide was excreted. Plasma protein binding of triptonide rate was about 75%.     

An investigation on plasma progesterone levels during pregnancy and at parturition in the Ivesi sheep

We have investigated the toxicity of dose-escalation of BCNU, etoposide and melphalan ('BEM') chemotherapy with autologous stem cell transplantation in patients with haematological malignancies. Seventy-two patients with haematological malignancies were treated with BCNU (600 mg/m2, 450 mg/m2 or 300 mg/m2), etoposide 2 g/m2 and melphalan 140 mg/m2 followed by autologous bone marrow transplantation (ABMT), n = 51, or autologous peripheral blood progenitor cell transplantation (APBPCT), n = 21. Liver and pulmonary function was monitored pretransplant and at regular intervals post-transplant. Mucositis was graded daily during in-patient stay. There was a significantly higher incidence of symptomatic pulmonary toxicity in the patients who received BCNU at 600 mg/m2 than in the other two groups, and there was a significant increase in the incidence of asymptomatic decrease in carbon monoxide (KCO) in the patients who received BCNU 450 mg/m2. There was no significant difference between the three groups in the incidence and severity of mucositis or in the incidence of transiently abnormal liver function. We conclude that etoposide at 2 g/m2 can be used without unacceptable mucositis. BCNU at 600 mg/m2 is associated with an unacceptably high incidence of lung toxicity, but at 450 mg/m2 there is minimal symptomatic lung toxicity.