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Biomedical subjects

I A Sutherland

Publications and source records attributed to I A Sutherland.

At least 37 records · Page 2Linked to original sources
PubMed2000

Altered peripheral vascular response of women with and without pelvic pain due to congestion.

OBJECTIVE: To test the hypothesis that women with pelvic venous congestion have a reduction of reactivity of their peripheral circulation. DESIGN: Comparison was made between 20 women with chronic pelvic pain due to congestion and a control group of 15 pain-free women matched for age, parity and body weight. A comparison of these results was made with those from six postmenopausal women taking hormone replacement therapy. METHODS: Study and control groups were investigated during the mid-follicular phase of the menstrual cycle (days 5-9) and the mid-luteal phase (days 19-23). The study group was also investigated during the fifth month of treatment with suppression of ovarian activity with leuprorelin or medroxyprogesterone acetate or six months after hysterectomy and bilateral salpingo-oophorectomy. Head-up tilt sufficient to increase intra-vascular pressure in the toe by a standard 40 mmHg was used as a means of raising venous pressure in the lower limb. Skin capillary red blood cell velocity (flux) was measured using a laser Doppler flow probe placed over the pulp of the big toe. Heart rate and blood pressure were also recorded. The change in skin blood flow following head-up tilt was expressed as a percentage of baseline flow in the supine position. MAIN OUTCOME MEASURES: Percentage change in skin red blood cell flux, heart rate and blood pressure in response to 40 degrees head-up tilt. RESULTS: In the control group the median response to head-up tilt in the follicular phase was one of a reduction in flux, whereas in the luteal phase it was more variable ranging from an increase to a decrease in flux. The responses in the pelvic congestion group in both the follicular and luteal phases were similar to those of the control group in the luteal phase. A small but significant increase in heart rate in response to tilt in the pelvic pain group, compared with the control group, was interpreted as being due to a fall in venous return. Treatment of the pelvic congestion group by medical suppression of ovarian activity or total hysterectomy with bilateral salpingo-oophorectomy resulted in a significant change in response to head-up tilt from the variable type of luteal response to one of a more constant reduction in flux, similar to that of the control group in the follicular phase. A reduction in flux was also found consistently in postmenopausal women. CONCLUSION: The study confirms the hypothesis that women with pelvic pain due to congestion show a change in peripheral vascular reactivity which returns to normal after suppression of ovarian activity. It seems likely that some alteration of normal ovarian function is responsible for the observed changes in peripheral blood flow in response to a rise in venous pressure in women with pelvic congestion.

Blood Flow Velocity↗
PubMed1999

The effect of continuous drug exposure on the immune response to Trichostrongylus colubriformis in sheep.

The effect of albendazole (ABZ)-capsule (CRC) administration on parasite establishment and immunity to ABZ-resistant (RES) and -susceptible (SUS) T. colubriformis was measured in Romney lambs. During 12 weeks of twice-weekly dosing with 3000 parasite larvae (L3), eggs were observed in faeces from CRC-treated and untreated lambs given RES L3, but not CRC-treated lambs given SUS L3. Following the period of trickle challenge all lambs were drenched and, 1 week later, dosed with 20000 SUS L3. Resulting worm burdens were higher in control lambs than in those previously treated with CRCs and challenged with SUS, which in turn were higher than those in the CRC-treated or -untreated lambs previously challenged with RES L3. During the period of trickle challenge, the number of peripheral eosinophils and titres of anti-L3 and anti-adult antibody were raised only in those groups given RES L3. There was no effect of CRC administration. Following drench and challenge, antibody titres and eosinophil numbers increased in the control animals but not in those groups which had received previous trickle infection. The results demonstrate that the larval challenge alone resulted in incomplete though substantial protection against subsequent parasite challenge. The use of CRCs may potentially impact on subsequent animal performance and selection for anthelmintic resistance through a reduced level of immunity.

Albendazole↗
PubMed1999

The establishment rate of Ostertagia circumcincta and Trichostrongylus colubriformis in lactating Romney ewes.

The ability of lactating Romney ewes to resist establishment of ingested infective-stage larvae (L3) of Ostertagia circumcincta and Trichostrongylus colubriformis was measured in the field. Three groups of seven single-lamb-bearing ewes were selected on the basis of uniformity of lambing date from a large flock held on pasture. Either 2, 4 or 6 weeks after parturition, groups of ewes were dosed with 24000 L3 of known oxfendazole-resistant parasite strains; 12000 of each species. Ten to 14 days later the ewes, along with their lambs, were transferred from the field to indoor pens. Twenty-five days after the challenge dose the ewes were drenched with oxfendazole to remove any field-derived infection and 3 days later slaughtered for worm counts. Mean establishment of the resistant parasites was low at all times, with the highest rate recorded being 6.1% for O. circumcincta 2 weeks after parturition. Establishment of O. circumcincta 4 and 6 weeks after parturition, and of T. colubriformis at all times, never exceeded 2%. By comparison, mean establishment in lambs held indoors and parasite free for 13 weeks prior to infection, was 24.9% and 47.1% for O. circumcincta and T. colubriformis, respectively. These results indicate that the lactating ewes were exhibiting a substantial ability to prevent establishment of ingested larvae. The results of this and other similar studies suggest that the dynamics of parasitism in lactating Coopworth and Romney ewes in New Zealand is substantially different to that in Merino ewes in Australia, and that these differences influence optimal strategies for the management of anthelmintic resistance in the two countries.

Animals↗
PubMed1999

The immune response of sheep to larval challenge with Ostertagia circumcincta and O. ostertagi.

One of three groups of sheep was challenged twice-weekly with infective-stage larvae (L3) of the sheep parasite O. circumcincta, another with the cattle parasite O. ostertagi while the third received no larval challenge. Positive faecal egg counts (FEC) and a rise in plasma pepsinogen levels were observed only in those animals given O. circumcincta. Anti-O. circumcincta L3 IgG titres were rapidly elevated during parasite challenge with either O. circumcincta or O. ostertagi. Throughout the experiment, no rise in anti-adult IgG titres or eosinophil numbers was observed in peripheral blood in any group. On evidence of self-cure of the trickle-infection, determined by a reduction in FEC, all groups were drenched and challenged with 15,000 O. circumcincta L3. No effect of previous challenge on parasite establishment or FEC was observed, although egg viability was significantly reduced in both groups given prior challenge. Significant differences in adult female worm length were observed between groups. Those recovered from animals previously challenged with O. circumcincta were shorter than from those given O. ostertagi which were in turn shorter than those from previously unchallenged animals. In utero egg counts were significantly lower in worms from animals previously challenged with O. circumcincta than in those from unchallenged control animals. The results indicate that a level of immunity to O. circumcincta can be conferred by exposure to O. ostertagi.

Abomasum↗
PubMed1999

Moxidectin: persistence and efficacy against drug-resistant Ostertagia circumcincta.

In order to determine whether the efficacy of moxidectin against Ostertagia circumcincta is enhanced by its persistency, therapeutic efficacy was compared at intervals after treatment and with that of ivermectin, a closely related but more transient endectocide. Groups of 7-month-old New Zealand Romney lambs were infected with a strain of O. circumcincta known to be resistant to moxidectin. At patency of the infections, groups of lambs were treated with either moxidectin or ivermectin at the manufacturer's recommended dosages, or left untreated. At 3, 6 and 10 days post-treatment, faecal egg count was measured and groups of lambs were slaughtered for estimation of adult worm burden. Drug-resistant worm burdens were significantly reduced in those animals treated with moxidectin but not in those treated with ivermectin. No effect of time of slaughter on worm burden was observed with either drug, demonstrating that the higher therapeutic efficacy of moxidectin against this parasite was not due to an increased period of drug exposure. Faecal egg counts in the moxidectin treated animals increased with time after treatment indicating a temporary suppression of egg output by surviving worms. The implications of these findings on selection for anthelmintic resistance are discussed.

Animals↗
PubMed1998

Theileria annulata: the expression of two novel macroschizont antigens on the surface of infected mononuclear cells differs during in vitro attenuation of a virulent cell line.

The first part of this study of the biological mechanisms underlying attenuation of virulent Theileria annulata macroschizont-infected cell lines screened four pairs of T. annulata (Hisar) in vivo- and in vitro-derived macroschizont-infected cell lines (lines) and identified a single in vivo-derived line, which induced lethal tropical theileriosis. The other seven lines were relatively avirulent. Analysis of the clinical, hematological, and parasitological responses of cattle immunized with different passages of the virulent line after in vitro culture showed that it was partly attenuated by passage (p) 50 and avirulent by p130. Clones representing the three glucose phosphate isomerase (GPI) isotypes, which constituted the newly isolated virulent culture, were obtained from p3 by limiting dilution; p50 and p130 consisted of one isotype. The second part of the study raised monoclonal antibodies (MAbs) against macroschizont-infected cells, as reagents for detecting antigenic differences between virulent and avirulent parasites, and identified two MAbs that recognized the surface of infected cells as well as macroschizonts. MAb EU1 recognized an antigen expressed by all the lines tested, whether in vitro- or in vivo-derived, whether uncloned or cloned, and irrespective of extent of subpassage in culture. MAb EU106 recognized an antigen whose expression by the virulent line and its clones disappeared on passage in culture. This antigen was not expressed at all by the avirulent in vitro-derived line prepared with cells from the same calf. Both antigens were expressed by lines infected with other stocks of T. annulata, including two lines known to induce lethal disease. The different profiles of expression of the two novel antigens, recognized by MAbs EU1 and EU106, by the line undergoing attenuation suggest (1) that the two antigens interact differently with the bovine immune system; and (2) that there are two, very different, potential roles for these antibodies in the development of vaccines against T. annulata infections.

Animals↗
PubMed1998

Variation between hosts in the developmental success of the free-living stages of trichostrongyle infections of sheep.

Variation between hosts of different ages and genotypes in the developmental success of trichostrongylid parasite eggs from sheep was investigated in two trials. The percentage development to infective third-stage larvae of eggs collected from lambs and adult ewes infected with Ostertagia circumcincta was compared in an indoor trial. In addition, sheep previously bred for either high or low faecal egg count and grazed outdoors on parasite contaminated pasture were sampled; egg development, faecal egg count, generic profile and faecal dry matter were measured. In both trials, development to L3 was significantly lower in eggs derived from adult ewes than from lambs and, in the field trial, from animals selected for low faecal egg count. The observed differences could not be accounted for by variations in faecal egg count, faecal dry matter content nor by differences in the generic composition of worm egg output. Although not shown conclusively, the results are consistent with an immune mechanism influencing the development of free-living stages of gastrointestinal nematodes outside the host. These results have significant implications for our understanding of parasite epidemiology, particularly as it relates to sources of pasture contamination.

Age Factors↗
PubMed1998

The effect of continuous drug exposure on the immune response of lambs challenged with drug-susceptible or drug-resistant nematode larvae.

Groups of lambs either with or without controlled-release albendazole (ABZ) capsules (CRCs) were challenged twice weekly for 6 weeks with either drug-susceptible or drug-resistant Ostertagia circumcincta and Trichostrongylus colubriformis. Groups with and without CRCs remained unchallenged as controls. There was minimal establishment of drug-susceptible parasites of either species in those lambs with CRCs. However, drug-resistant parasites of both species established adult worm burdens in the presence of the capsules. The humoral immune response, as measured by the serum antilarval (L3) antibody (Ab) titre, was pooled for weeks 4-6 and compared for each group. With the exception of anti-T. colubriformis Ab in group 2, anti-L3 Ab titres were significantly higher in all the parasite-challenged groups as compared to the control animals. Also, with the exception of anti-resistant O. circumcincta Ab levels in the CRC-treated animals (group 5), no significant difference was observed in Ab titres between the four groups challenged with either resistant or susceptible larvae. The results demonstrate the inability of CRCs to prevent establishment of drug-resistant parasites and that immune stimulation is not inhibited by the capsules.

Albendazole↗
PubMed1997

Prophylactic efficacy of persistent anthelmintics against challenge with drug-resistant and susceptible Ostertagia circumcincta.

Three groups of newly-weaned Romney lambs were given either a standard oral dose of albendazole, a controlled-release capsule containing albendazole, or a standard oral dose of moxidectin. At 10, 20, 30 and 40 days after treatment, sub-groups of lambs were given 10,000 infective-stage larvae of either a drug-resistant or a drug-susceptible strain of Ostertagia circumcincta. The recommended oral dose of albendazole removed 32 per cent of the resistant strain and over 99.9 per cent of the susceptible O. circumcincta. The recommended oral dose of moxidectin removed 91 per cent of the resistant strain and over 99.9 per cent of the susceptible parasites. None of the lambs treated with controlled-release capsules was challenged at 20 or 30 days after treatment. Twenty-one days after challenge, samples of faeces were taken to determine the presence of nematode eggs and cultured to establish the proportion of eggs developing to infective-stage larvae (L3). Abomasa were recovered after slaughter and worm burdens determined. In the lambs given controlled-release capsules only the resistant parasites were able to establish, and there were significantly fewer than in the lambs treated orally with albendazole. The proportion of the eggs from resistant parasites which developed to L3 was not reduced by the presence of the capsules. Oral moxidectin provided no protection against the establishment of the resistant strain and viable L3 were recovered after challenge with resistant parasites 10 days after treatment; however, the establishment of susceptible O. circumcincta was reduced by more than 99 per cent. The establishment of the susceptible parasites in the lambs treated with moxidectin increased with time and was not significantly lower than in the other groups by 30 days after treatment.

Administration, Oral↗
PubMed1997

The death rate of Ostertagia circumcincta and Trichostrongylus colubriformis in lactating ewes: implications for anthelmintic resistance.

Lactating adult Romney ewes were infected, 4 weeks post-lambing, with benzimidazole (bz) resistant strains of Ostertagia circumcincta and Trichostrongylus colubriformis. Commencing 4 weeks after the initial infection the ewes were subjected to challenge 3 times weekly with 5000 L3 of bz-susceptible strains of both parasite species. At weekly intervals over the following 6 weeks, groups of ewes were drenched with a bz anthelmintic (oxfendazole) to remove bz-susceptible parasites and slaughtered to determine adult worm burdens of the bz-resistant parasites. The O. circumcincta infection declined exponentially with a mean daily death rate of 10.6% day-1 and no worms were recovered after 4 weeks or more of challenge. The T. colubriformis infection did not decline significantly over the 6 weeks of continuous challenge, indicating that the death rate could not be distinguished from zero. The upper 95% confidence limit for the death rate of T. colubriformis was 4.9%. The implications of these death rates on selection for drug resistance following ewe drenching during the post-partum period are discussed with selection pressure likely to be greater for T. colubriformis than for O. circumcincta.

Animals↗
PubMed1996

Theileria annulata: altered gene expression and clonal selection during continuous in vitro culture.

Kept in continuous in vitro culture, the protozoan parasite Theileria annulata gradually loses virulence when inoculated into cattle. These attenuated cell lines form the basis of the in vitro live vaccines which have been used successfully to control tropical theileriosis in several endemic regions. In the study reported here, events occurring during in vitro culture of an Indian (Hisar) cell line, which may be associated with the reduction in virulence, have been investigated. Hybridization with two polymorphic DNA probes following Southern blotting showed that selection of particular parasite genotypes occurs very rapidly with culture; a novel hybridization pattern is observed with both probes after 50-100 passages in vitro. In addition to this selection process, immunofluorescence studies using a monoclonal antibody which specifically recognizes virulent T. annulata revealed alterations in antibody reactivity following in vitro culture. This loss of reactivity was observed in three cloned cell lines derived from the early, virulent Hisar line and implies that phenotypic changes resulting from alterations to parasite gene expression are taking place during the attenuation process. When considered with the results from in vivo infections with serial passages of this cell line, it can be proposed that both altered gene expression and selection may be involved in the loss of pathogenicity of T. annulata during continuous in vitro culture.

Animals↗
PubMed1995

Suppressor macrophages in Trypanosoma brucei infection: nitric oxide is related to both suppressive activity and lifespan in vivo.

African trypanosome infections cause immunosuppression in both experimental rodent and natural hosts. One characteristic of this is an eliciting of suppressor macrophages which results in an unresponsiveness in lymphocytes. Macrophages from Trypanosoma brucei-infected mice have previously been shown to produce high levels of nitric oxide (NO). Using model systems based on in vivo macrophage transfer and drug cure, we have sought to determine the relationship between NO and suppressed lymphocyte responses. Peritoneal macrophages from T. brucei-infected mice inhibited the Concanavalin A (Con-A) response of spleen cells from syngeneic recipients 3-4 days after transfer in vivo due to the activity of suppressor macrophages. When macrophage NO synthesis was inhibited either in vitro or in vivo the suppressive effects were partially abrogated. These data provide evidence of a role for NO in mediating immunosuppression during murine T. brucei infection. Suppression in spleens of mice receiving suppressor macrophages was transient, with total recovery of spleen cell mitogen responses six days after transfer. Suppression and recovery was found to coincide with the presence or absence (respectively) of donor macrophages in recipient spleens. When T. brucei-infected mice were treated with a curative dose of a trypanocide there followed a recovery of lymphocyte responsiveness after a period of 4-5 days, and this directly correlated with a reduction of macrophage NO synthesis to control levels both in vivo and in vitro. The apparent loss of suppressor macrophage activity after 4-6 days in both drug cured animals and recipients of macrophage transfer was shown to be due to NO-mediated apoptosis of these cells.

Animals↗
PubMed1994

Trypanosoma brucei is protected from the cytostatic effects of nitric oxide under in vivo conditions.

In mice infected with Trypanosoma brucei, splenic and peritoneal macrophages release substantial amounts of nitric oxide (NO). The production of NO by activated macrophages has been reported to be a nonspecific immune-effector mechanism against several parasites, and in this work we investigate the role of NO in killing T. brucei. Addition of bloodstream trypanosomes to peritoneal macrophages activated in vitro resulted in an NO-dependent inhibition of parasite growth. This effect was totally abrogated when dilutions of whole blood were included in the cultures, suggesting that bloodstream parasites such as T. brucei are not susceptible to NO-mediated killing in vivo.

Animals↗
PubMed1994

Correction of the non-uniform spatial sensitivity of electrical impedance tomography images.

One of the clinical applications of electrical impedance tomography (EIT) is the measurement of volume changes of body fluids. However, the spatial sensitivity of images produced by the Sheffield Mark I system is non-uniform and if quantitative comparisons of resistivity images resulting from volume changes are to be mad, this non-uniformity must be corrected for. All experimental data were collected from a phantom consisting of semi-permeable membrane tubes fixed vertically at different distances from the centre of a cylindrical tank which was filled with a saline solution of resistivity 5 omega m. Individual images were obtained when each tube was filled with a saline solution of resistivity 1.5 omega m. Analysis of these images, using the resistivity integral described by Thomas et al, yielded the sensitivity of EIT at different positions within the tank. Combinations of tubes were then filled with saline (1.5 omega m) and an image produced for each combination. Cross sections of the images were taken and used to confirm that the principle of superposition is valid for EIT. A simple pixel scaling correction, derived from the sensitivity data, was then applied to the images and the results re-analysed to demonstrate a reduction in volume measurement error. The application of this correction to in vivo images is discussed.

Electric Impedance↗
PubMed1993

Alterations in drug transport in resistant Trypanosoma congolense.

The transport of isometamidium chloride (Samorin) in Trypanosoma congolense which were either sensitive or resistant to this widely used trypanocide was studied in vitro. Significantly lower amounts of drug were accumulated over time by resistant than by sensitive trypanosomes. While no direct evidence could be obtained, indirect observations implied the involvement of an increased efflux of drug from the resistant trypanosomes. In both the resistant and sensitive parasites, drug transport was found to be mediated by an energy-dependent, specific process, presumably receptor-mediated. However, the specificity of the putative receptors was altered in the drug-resistant parasites. It is proposed that an alteration or replacement of a specific receptor in isometamidium chloride-resistant T. congolense results in an increased efflux of the drug and that this increased efflux at least partially mediates the reduction in sensitivity to the compound.

Animals↗
PubMed1993

Acetylcholinesterase in infective-stage larvae of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis resistant and susceptible to benzimidazole anthelmintics.

The amounts of acetylcholinesterase (AChE) in homogenates of infective-stage larvae of strains, from different countries, of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis resistant or susceptible to benzimidazole (BZ) anthelmintics, were compared using a rapid colorimetric assay. The levels of AChE were much greater in those strains which were BZ-resistant than in BZ-susceptible populations. The larvae of susceptible and resistant H. contortus contained less AChE than did the larvae of the other two species. One-way analysis of variance showed that the observed differences between susceptible and resistant strains were significant in each of the species studied. It is suggested that the extra enzyme may act as an anthelmintic-detoxifying enzyme, may inactivate the active site of the anthelmintic or may prevent binding of the anthelmintic to its receptor.

Acetylcholinesterase↗
PubMed1992

Therapeutic activity of isometamidium chloride in Boran cattle against a tsetse-transmitted clone of Trypanosoma congolense with a low level of drug resistance.

Experiments were conducted with a clone of Trypanosoma congolense, IL 3580, which exhibited a low level of resistance to isometamidium chloride. Five cattle were treated intramuscularly with isometamidium chloride at a dose rate of 0.5 mg kg-1 body weight (BW) and challenged 28 days later with 5 Glossina morsitans centralis infected with T. congolense IL 3580. All 5 cattle and 15 untreated steers challenged on the same day became parasitaemic by day 15 post-infection. Thus, at a dose of 0.5 mg kg-1 BW, the prophylactic action of isometamidium chloride did not extend to 28 days following treatment. Subsequently, the 20 steers were divided into 4 groups of 5 animals each and treated with isometamidium chloride at one of the following dose rates; 0.5 or 1.0 mg kg-1 BW intramuscularly and 0.5 or 1.0 mg kg-1 BW intravenously (Groups A, B, C and D, respectively). Group A consisted of the 5 animals that had previously been treated with isometamidium chloride. Animals relapsed in all groups except those in Group B, treated intramuscularly with isometamidium chloride at a dose of 1.0 mg kg-1 BW. Four of the 5 animals in Group A, treated intramuscularly with isometamidium chloride at a dose of 0.5 mg kg-1 BW relapsed following a mean interval of 16 days post-treatment. Similarly, infections in all animals in Groups C and D, given intravenous injections of isometamidium chloride at a dose of 0.5 and 1.0 mg kg-1 BW, respectively, were not eliminated as a result of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗