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N C Smith

Publications and source records attributed to N C Smith.

At least 55 records · Page 3Linked to original sources
PubMed1996

The effect of BCG, zymosan and Coxiella burnetti extract on Eimeria infections.

Infection of animals with species of Eimeria induces a hyper-reactivity to endotoxin as manifest by a greatly increased capacity of infected animals to produce TNF in response to LPS in vivo compared with uninfected animals. This finding indicates priming for hyperactivation of macrophages by Eimeria infection and raises the possibility that non-specific triggering of macrophages by agents such as Bacille Calmette-Guerin (BCG), zymosan or Coxiella burnetti extract may be a simple means of control for coccidiosis. However, all of these agents enhanced oocyst excretion in mice, rats or chickens infected with Eimeria vermiformis, Eimeria nieschulzi or Eimeria tenella, respectively, without affecting the patent period.

Animals↗
PubMed1996

Bizarre parosteal osteochondromatous proliferation: a review of seven cases.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare tumour-like condition mostly affecting the tubular bones of the hands and feet. Although it recurs in 50% of cases after local excision, it is a form of heterotopic ossification and its behaviour is otherwise benign. The present study describes seven cases of BPOP collected by the Bone Tumour Registry of New South Wales. METHODS: Clinical data, radiographs and histological specimens collected by the Bone Tumour Registry of New South Wales were examined, and further clinical data were sought from the referring doctor where necessary. RESULTS: Six males and one female aged 18 to 37 years (median 30 years) presented between 1988 and 1995. There were three cases involving the hands, three involving the feet and one involving the distal humerus. Initial treatment was by local excision in all cases. There was local recurrence in three cases. The initial diagnosis was wrong in five of the seven cases. Radiologically, BPOP appears as a well-defined tumour arising directly from the bony cortex, without periosteal reaction or change to the underlying bone. Histologically, a large amount of hypercellular cartilage shows maturation to trabecular bone, which frequently contains spindle cells in the intertrabecular spaces. CONCLUSION: BPOP is a rare, locally recurrent but otherwise benign condition of bone which must be distinguished from more sinister lesions such as parosteal osteosarcoma and chondrosarcoma.

Adolescent↗
PubMed1996

Histamine H3-receptor-mediated inhibition of calcitonin gene-related peptide release from cardiac C fibers. A regulatory negative-feedback loop.

Antidromic stimulation of cardiac sensory C fibers releases calcitonin gene-related peptide (CGRP), which increases heart rate, contractility, and coronary flow. C-fiber endings are closely associated with mast cells, and CGRP may release mast-cell histamine. Because prejunctional histamine H3-receptors inhibit transmitter release from autonomic nerves, we tested the hypothesis that H3-receptors modulate CGRP release in the heart. CGRP released by bradykinin in the electrically paced guinea pig left atrium and by capsaicin in the spontaneously beating isolated heart caused marked positive inotropic and chronotropic effects, respectively. Capsaicin significantly enhanced the overflow of CGRP (fivefold) and histamine (twofold) into the coronary effluent. All of these effects were prevented by prior chemical destruction of C fibers in vivo. The H3-receptor agonist imetit attenuated the inotropic response to bradykinin by 50%. Imetit also decreased the capsaicin-induced tachycardia and the increase in CGRP overflow by 50%. Imetit, however, did not modify the response to exogenous CGRP. The effects of imetit were blocked by the H3-receptor antagonist thioperamide. Notably, thioperamide by itself potentiated the capsaicin-evoked increases in heart rate and CGRP overflow (by 25% and 50%, respectively). Thus, our findings identify a negative-feedback loop, whereby CGRP releases histamine from cardiac mast cells and histamine in turn inhibits CGRP releases by activating H3-receptors on C-fiber terminals. Because CGRP release is augmented in pathophysiological conditions, such as septic shock, heart failure, and acute myocardial infarction, modulation of CGRP release may be clinically relevant.

Animals↗
PubMed1996

Effects of ozone and airway inflammation on glutathione status and iron homeostasis in the lungs of horses.

OBJECTIVE: To investigate the effects of ozone and airway inflammation on indices of oxidant injury in horses. ANIMALS: 5 clinically normal horses and 25 horses referred for poor performance. PROCEDURE: Blood, tracheal wash, and bronchoalveolar lavage fluid samples were collected before and after ozone exposure (n = 5) or from clinical cases (n = 25), and were analyzed for reduced glutathione (GSH), glutathione disulfide (GSSG), and free and total iron (Fe) values. A scoring system (0 to 5) was used to assess airway inflammation on the basis of clinical signs and cytologic analysis of the tracheal wash and bronchoalveolar lavage fluid samples. RESULTS: Ozone induced significant (P < 0.05) increases in GSH (195.4 +/- 68.5 microM), GSSG (19.4 +/- 6.4 microM), and free (25.5 +/- 16.1 microM) and total (93.1 +/- 13.4 microM) Fe values in the pulmonary epithelial lining fluid, compared with preozone samples (49.2 +/- 18.6, 2.4 +/- 1.2, 0.0, and 33.1 +/- 5.9 microM, respectively). The presence of airway inflammation (19/25) was associated with high GSSG and free and total Fe, but not GSH, values in epithelial lining fluid, compared with values for clinically normal horses (6/25). There were no differences in the systemic values of GSH, GSSG, and free and total Fe between any of the groups. A strong correlation (r = 0.84; P < 0.001) existed between inflammation score and the glutathione redox ratio (GSSG/[GSH + GSSG]) in the 25 horses admitted for clinical examination. CONCLUSIONS: Oxidant injury in the lung will induce changes in the glutathione status and Fe homeostasis that could affect pathogenesis of the disease. CLINICAL RELEVANCE: Measurement of indices of oxidant injury may be useful in the diagnosis of airway inflammation and the response to inhaled oxidants.

Animals↗
PubMed1995

Simultaneous quantitation of oxidised and reduced glutathione in equine biological fluids by reversed-phase high-performance liquid chromatography using electrochemical detection.

A change in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) can be used to indicate oxidative stress in vivo. A rapid and highly sensitive isocratic reversed-phase high-performance liquid chromatographic method using coulometric electrochemical detection (LCEC) has been developed to simultaneously detect GSH and GSSG in equine biological fluids. Perchloric acid was used to extract GSH and GSSG from equine plasma and haemolysates, and methanol was used to deproteinise bronchoalveolar lavage fluid samples. Injection of extracts onto a Hypersil ODS HPLC column produced well resolved peaks corresponding to GSH and GSSG. The concentrations of GSH and GSSG found in equine haemolysates were similar to those previously found in humans and laboratory animals, although, to the authors' knowledge, previous attempts to measure GSH and GSSG in bronchoalveolar lavage fluid using LCEC have been unsuccessful. This method can be used to measure the GSH redox ratio in biological fluids during physiological conditions that may induce oxidative stress, such as exercise and disease.

Animals↗
PubMed1995

A randomized prospective trial comparing single dose prostaglandin E2 vaginal gel with forewater amniotomy for induction of labour.

A prospective randomized parallel-group study was carried out to compare the efficacy of a single dose vaginal prostaglandin E2 gel with forewater amniotomy for induction of labour at term in 260 parturients (110 primigravid and 150 parous women) with low risk pregnancy and favourable cervix. In the prostaglandin E2 (PGE2) managed group, the primigravidae were treated with 2 mg PGE2 gel and parous patients with 1 mg PGE2 gel. Forewater amniotomy was performed 4 h later, or sooner if women requested analgesia. In the amniotomy group, artificial forewater amniotomy was carried out and a repeat cervical assessment done 4 h later, or sooner if women requested analgesia. In both groups, intravenous oxytocin was established if there was evidence of disordered uterine activity, 6 h after the start of initial intervention. An assessment of consumers' views was carried out by using a standardized questionnaire completed 48 h after delivery. There was a significant reduction in the requirement for oxytocin augmentation in women treated with PGE2: primigravidae, odds ratio (OR), 0.27 and 95% confidence interval (CI), 0.12-0.61; multiparae, OR, 0.19 and 95% CI, 0.08-0.45. Fewer primigravidae managed with PGE2 gel required epidural analgesia (OR, 0.16; 95% CI, 0.06-1.00). Fewer parous women managed with PGE2 gel required parenteral opiates (OR, 0.44; 95% CI, 0.23-0.85) and more women required inhalation analgesia or no analgesia (OR, 2.22; 95% CI, 1.76-2.79). The intervention to delivery intervals were shortened in PGE2 groups independent of parity but the differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Eimeria maxima gametocyte antigens: potential use in a subunit maternal vaccine against coccidiosis in chickens.

Affinity-purified gametocyte antigens (APGA) from Eimeria maxima, emulsified in Freund's adjuvant, were injected intramuscularly into breeding hens on two or three occasions. As a result, progeny of the immunized hens were partially immune to infection with E. maxima, Eimeria tenella and Eimeria acervulina (with a reduction in total oocyst output of 45-63% as compared with progeny of untreated hens). Thus, APGA in Freund's adjuvant appears to have great potential as part of a maternally applied vaccine against coccidiosis. The ability of APGA to induce partial cross-species protection is most probably due to the existence of conserved epitopes in the different species as indicated by comparative Western blots of E. maxima and E. tenella. Surprisingly, Freund's adjuvant by itself also induced significant levels of maternal immunity to coccidiosis (with a 12-35% reduction in oocyst output in the progeny). In contrast to the purified antigens or Freund's alone, crude extracts from gametocytes as well as other developmental stages, induced little if any significant maternal immunity despite provoking the production of large amounts of parasite-specific IgG, including antibodies to APGA. This result indicates that a successful maternal vaccine against coccidiosis requires, in addition to good recognition of protective antigens, the exclusion of irrelevant antigens from the vaccine preparation.

Animals↗
PubMed1995

Cytokine and immunoglobulin subclass responses of rats to infection with Eimeria nieschulzi.

SIV rats infected with a high dose (50,000 oocysts) of Eimeria nieschulzi displayed clinical symptoms of coccidiosis such as diarrhoea (days 6 and 7 post-primary infection) and weight loss (days 6-8 post-primary infection) and were completely immune to challenge with a similar dose. The ability of rats to produce tumour necrosis factor (TNF) in vivo was enhanced during the period of oocyst excretion in the primary infection but significant production of TNF did not occur after challenge infection. Thus, TNF does not appear to be an important factor in resistance to infection with E. nieschulzi but may play some role in resistance to primary infection and in the pathology associated with E. nieschulzi infection. Parasite-specific serum IgM levels (measured by enzyme-linked immunosorbent assay) were also increased during primary infection but returned to background levels at the end of the patent period and were not affected by challenge infection. In contrast to TNF and IgM, serum concentrations of E. nieschulzi-specific IgG1, IgG2a, IgG2b, IgG2c and intestinal tissue levels of IgA did not begin to increase until after day 12 post-primary infection, reached peak levels between days 20 and 30 post-primary infection and were slightly increased by challenge infection.

Animals↗
PubMed1995

The pharmacokinetics or oral and intravenous allopurinol and intravenous oxypurinol in the horse.

The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e(-25.14t) + 159.93e(-10.96t) for allopurinol and Cp = 321.09e(-9.72t) + 82.39e(-0.44t) for oxypurinol, with an elimination half-life (t1/2 beta) of 0.09 h and an area under the curve (AUC) of 19.8 mumol.h/L after intravenous administration, while the t1/2 beta and AUC of oxypurinol were 1.09 h and 231 mumol.h/L, respectively. The bioavailability of allopurinol was low (14.3%), although no allopurinol was detected in the plasma of two horses after oral administration of allopurinol was equivalent to that of intravenously injected oxypurinol. The results suggest that allopurinol is rapidly metabolised in vivo and that the majority of the pharmacological activity of allopurinol in the horse may result from the action of the active metabolite, oxypurinol.

Administration, Oral↗
PubMed1995

Specific IgG1 and IgG2 antibody responses of dogs to Leishmania infantum and other parasites.

Sera from dogs naturally infected with Leishmania infantum were analysed for the IgG subclass specificity of their antibody response by ELISA. Dogs infected with L. infantum produced both IgG1 and IgG2 antibodies with IgG2 being associated with asymptomatic infections and IgG1 being associated with disease (symptomatic dogs, non- or low-responsive to chemotherapy). The differential responses of IgG1 and IgG2 serum antibodies in asymptomatic and symptomatic dogs may indicate a dichotomous immune response to infection with L. infantum. To confirm this, on a broader scale, sera from dogs naturally exposed to an asymptomatic protozoan infection, Toxoplasma gondii, were also analysed as were sera from dogs exposed to the helminths, Dirofilaria immitis and Toxocara canis. Antibodies specific for T. gondii antigen detected in sera from 17 dogs were of the IgG2 subclass only. Both IgG1 and IgG2 antibodies to D. immitis and T. canis were present in the sera of naturally infected dogs but IgG1 appeared to be the predominant subclass. Furthermore, in dogs experimentally infected with T. canis, selective regulation of IgG2 and IgG1 responses was apparent since production of the two subclasses occurred at different times following infection, with IgG2 levels declining as IgG1 levels rose. Thus, the analysis of IgG subsets in parasitized dogs provides evidence of a dichotomous response to infection: IgG2 is associated with asymptomatic protozoan infections and IgG1 is associated with helminth infections and disease caused by protozoan infection.

Animals↗
PubMed1994

Nippostrongylus brasiliensis: ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to gamma-interferon or tumour necrosis factor.

Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasma to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (< 1 ng/ml), though copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS-induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Maternal transfer of antibodies induced by infection with Eimeria maxima partially protects chickens against challenge with Eimeria tenella.

Infection of breeding hens with Eimeria maxima induces production of Eimeria-specific IgG antibodies which are transferred to hatchlings via the egg yolk and confer a high degree of maternal immunity against homologous challenge and partial immunity to infection with another important species, Eimeria tenella. As an example, in an experiment using hatchlings from eggs collected between days 28 and 39 after infection of the hens with 20,000 sporulated E. maxima oocysts, control chicks (challenged with 100 sporulated oocysts) excreted 6.8 +/- 1.2 million (mean +/- S.E., n = 10) or 5.8 +/- 1.2 million (n = 8) oocysts of E. maxima or E. tenella, respectively, compared to 0.9 +/- 0.4 million (n = 5) E. maxima oocysts or 2.2 +/- 0.4 million (n = 9) E. tenella oocysts excreted by hatchlings of infected hens. This represents an 87% reduction in oocyst excretion with regard to E. maxima and a 62% reduction in oocyst excretion with regard to E. tenella in the progeny of the infected hens. In another experiment, eggs were collected from days 28 to 37 and again from days 114 to 123 after infection of the hens with E. maxima and hatchling oocyst excretion rates were 82% and 62%, respectively, reduced for E. maxima and 43% and 41%, respectively, reduced for E. tenella in the progeny of hens infected with E. maxima compared to the progeny of uninfected hens. ELISA and Western blot analyses of maternally-derived IgG revealed a high degree of cross-reactivity to antigens of E. maxima and E. tenella.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Eimeria maxima: ELISA and western blot analyses of protective sera.

Infection of chickens with Eimeria maxima induces the production of parasite-specific antisera which can be used passively to protect naive chickens against infection. Globulin fractions of these antisera can also be used passively to protect chickens. Similarly, intramuscular injection of soybean lectin affinity purified gametocyte antigens of E. maxima in Freund's Complete Adjuvant induces production of antibodies which are maternally transferred and thereby protect hatchlings against E. maxima. ELISA analyses of serum pools having varying protective capacities revealed good correlations between passive protection and levels of anti-unsporulated oocyst, anti-sporulated oocyst, anti-merozoite and anti-gametocyte antibodies. Western blotting demonstrated that the sera mainly recognized a number of high molecular weight antigens in all developmental stages and that the intensity of the reactions reflected the degree of protection induced by the sera. Sera from birds immunized with gametocyte antigens also recognized high molecular weight antigens from all the developmental stages, with banding patterns remarkably similar to those observed for sera from infected birds. Taken together, these results indicate that antibodies can protect against infection with E. maxima and these antibodies may recognize and act against asexual and/or sexual stages of the parasite.

Animals↗
PubMed1994

Maternal transmission of immunity to Eimeria maxima: western blot analysis of protective antibodies induced by infection.

Infection of breeding hens with Eimeria maxima induces production of parasite-specific antibodies which are transferred, via the egg yolk, to hatchling chicks. These antibodies (immunoglobulin G) are highly protective, mediating up to a 97% reduction in oocyst excretion in challenged hatchlings. However, the degree of maternally derived immunity transferred by the hens to their offspring declines with increasing time after infection of the hens. This decline in immunity is directly related to declining immunoglobulin G titers. However, sera from highly protected hatchlings recognize only a very few E. maxima proteins on Western blots (immunoblots). In particular, a 230-kDa protein band is outstanding for its association with maternally derived immunity to E. maxima in hatchlings. This band was excised from a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) preparative gel of crude merozoite protein extract. The SDS-PAGE cutout was emulsified in Freund's adjuvant and injected, intramuscularly, into six breeding hens on two occasions, 2 weeks apart. Eggs were collected from these hens 28 to 39 days after the second injection, and the hatchlings from these eggs were challenged with 150 sporulated oocysts of E. maxima. Subsequent oocyst excretion in these hatchlings was, on average, 54% lower than oocyst excretion by control chicks but only 37% lower (significant at P < 0.05) than that by chicks from hens sham immunized with Freund's adjuvant. The latter result is apparently due to the ability of the adjuvant to induce production of antibodies which recognize Eimeria spp. and thereby transfer some degree of protection to hatchlings. These experiments indicate that protective, maternally derived immunoglobulin G antibodies may be useful for the identification of putative anticoccidial vaccine candidates.

Animals↗
PubMed1994

Maternal transmission of immunity to Eimeria maxima: enzyme-linked immunosorbent assay analysis of protective antibodies induced by infection.

Vaccination of broiler chickens against Eimeria infection is problematic because of the need to ensure that birds are protected from the time of hatching. We have therefore investigated the feasibility of protecting hatchling broilers via maternal transfer of protective antibodies from hens to their offspring. Oral infection of broiler breeder hens with 20,000 sporulated Eimeria maxima oocysts caused production of antibodies which were passed into the egg yolk and subsequently to hatchlings. The level of specific antibodies in the yolks to unsporulated oocysts, sporulated oocysts, merozoites, and gametocytes was assessed by enzyme-linked immunosorbent assays. The levels in yolks of antibodies to all developmental stages peaked 3 to 4 weeks after infection of the hens. Groups of 10 hatchlings were challenged at 3 days of age by oral infection with 100 sporulated E. maxima oocysts. In the first experiment, the mean 4-day (days 6 to 9 post-infection) total number of oocysts excreted in the feces of chicks from eggs collected 3 weeks after infection of the hens was (0.6 +/- 0.4) x 10(6) (mean +/- standard error) compared with (9.9 +/- 1.4) x 10(6) for the progeny of uninfected hens, which represents a greater than 90% reduction. However, oocyst excretion by chicks from eggs collected 7 or 8 weeks after infection of the hens was only 47 or 68% lower than control values, reflecting declining levels of protective antibodies. In a second experiment, in which the hens were somewhat older and pretreated by intramuscular injection of saline in the emulsifying agent, Arlacel A, the period for which protective antibodies were transferred to hatchlings was prolonged. Thus, oocyst excretion by challenged hatchlings from eggs collected for an 8-week period after infection of the hens was more than 90% lower than oocyst excretion by control chicks, and even hatchlings of eggs collected 19 weeks after infection of the hens showed a 60% reduction in oocyst output. In both experiments, the levels of immunoglobulin G (IgG) antibodies to all developmental stages in yolks or hatchling sera were very strongly correlated with maternally derived immunity to E. maxima. In contrast, parasite-specific IgM or IgA was not detectable, either in egg yolk or egg white. These results demonstrate the ability of IgG antibodies to protect against E. maxima in poultry, thus raising the possibility of using protective maternally derived IgG antibodies to identify potentially protective parasite antigens and indicating the feasibility of using maternal immunization as a means for parasite control.

Animals↗