Immunity to coccidiosis: stages of the life-cycle of Eimeria maxima which induce, and are affected by, the response of the host

An attempt was made to determine the relative importance of the different life-cycle stages of Eimeria maxima in the induction of immunity and also those stages most affected by the immune response of the host. In one experiment the life-cycle was controlled by chemotherapy but in all other experiments partial life-cycles were induced by transfers of infected mucosa between hosts. The results indicated that the second generation schizont stage is probably that most concerned in the induction of protective immunity and that sexual stages are most susceptible to immune inhibition. After initial inhibition in the immune host the earlier asexual stages were able to resume development when transferred to a susceptible host. The longer the period of exposure to the immune environment, the less able was the parasite to recover.     

Lack of correlation between microscopic lesion scores and gross lesion scores in commercially grown broilers examined for small intestinal Eimeria spp. coccidiosis

Comparisons were made between microscopic lesion scores (MLSs) and gross lesion scores (GLSs) in sections from small intestine of broilers during three routine coccidiosis screenings. The duodenal and jejunal GLS were determined and recorded by different evaluators. During each screening, 2-cm sections of duodenum and jejunum were collected, and sections of intestine were then scored using a microscopic lesion scoring system. No correlation between MLS and GLS was observed in duodenum in two out of three coccidiosis screenings, and no correlation was observed between MLS and GLS in jejunum in three out of three screenings. Our findings demonstrate that, if used alone in coccidiosis screening, GLSs can underestimate infections and may not provide a true representation of the magnitude of Eimeria maxima infection within broiler flocks.     

Prevention of salt-dependent cardiac remodeling and enhanced gene expression in stroke-prone hypertensive rats by the long-acting calcium channel blocker lacidipine

OBJECTIVE: To analyze the effect of the long-acting calcium channel blocker lacidipine on cardiovascular remodeling induced by salt loading in a genetic model of hypertension. DESIGN: We examined the influence of threshold doses of lacidipine, with little blood-pressure lowering effect, on cardiac weight and gene expression in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: SHRSPs (8-week-old) were randomly allocated to four groups: control, salt-loaded SHRSP and salt-loaded SHRSP treated with lacidipine at 0.3 and 1 mg/kg per day. Systolic blood pressure was measured by the tail-cuff method. At the end of 6 weeks of treatment, ventricles were collected and weighed. Ventricular messenger RNA was extracted and subjected to Northern blot analysis. RESULTS: Lacidipine (0.3 mg/kg per day) not only prevented the salt-dependent cardiac hypertrophy and the slight increase in systolic blood pressure induced by salt, but also prevented, largely or completely, salt-dependent increases in ventricular levels of several gene products: skeletal and cardiac alpha-actin, beta-myosin heavy chain (beta-MHC), type I collagen, long-lasting (L)-type calcium channel and preproendothelin-1. At a higher dose of 1 mg/kg per day, lacidipine further decreased systolic blood pressure below the level of control SHRSP, completely prevented salt-dependent overexpression of the beta-MHC gene and markedly attenuated salt-dependent overexpression of the transforming growth factor-beta1 gene. CONCLUSIONS: Lacidipine prevents the cardiac remodeling and enhanced gene expression induced by salt loading in SHRSP at doses that only minimally affect the high systolic blood pressure.     

Incremental bolus versus a continuous infusion of propofol for deep sedation/general anesthesia during dentoalveolar surgery

PURPOSE: This article compared the use of the traditional incremental bolus technique with the continuous infusion technique for the administration of propofol for deep sedation/general anesthesia. PATIENTS AND METHODS: Patients were sedated with midazolam and fentanyl and then had maintenance of an anesthetic state achieved with propofol administered by either of the two techniques. Data were collected to evaluate the overall surgical/anesthetic procedure, movement of the patient, and his or her hemodynamic status. RESULTS: Both groups received a mean maintenance dose of propofol exceeding 6 mg/kg/hr. However, the patients in the continuous infusion group received a statistically greater maintenance dose (continuous infusion + supplemental vs incremental bolus). All patients were maintained in a deep sedation/general anesthetic state. Respiratory and blood pressure values were comparable in both groups. However, the continuous infusion group showed improved hemodynamic stability manifested as fewer fluctuations in heart rate. Visual analog scale (VAS) questionnaires completed by the surgeon and surgical assistant reported less patient movement and improved surgical/anesthetic conditions with the continuous infusion technique. Recovery of the two groups was comparable. CONCLUSION: This study, although finding advantages in the continuous infusion technique, showed satisfactory conditions associated with both techniques.     

Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery

The concentrations of sulbactam and ampicillin were determined in sera and different abdominal tissues of 16 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 (eight patients) were given 1,000 mg of sulbactam with 2,000 mg of ampicillin by intravenous bolus injection (3 min). This dose was administered again after 2 h by bolus injection by the same route. Patients in group 2 (eight patients) were given the same initial dose of sulbactam-ampicillin by bolus injection (3 min). Then, a continuous infusion of 1,000 mg of sulbactam with 2,000 mg of ampicillin in normal saline was immediately started and was administered over a 4-h period. Blood samples were collected to determine peak (10 min) and trough (end of surgery) antibiotic levels. Serial blood samples were also collected at predetermined periods (at the time of opening and closing of the abdominal cavity and at the time of surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Similar levels of the drugs in serum were observed for the two regimens of administration, with trough sulbactam levels of 33 +/- 16 and 37 +/- 22 microg/ml in groups 1 and 2, respectively, and trough ampicillin levels of 72 +/- 55 and 79 +/- 47 microg/ml in groups 1 and 2, respectively. Similar sulbactam concentrations were observed in abdominal tissues whichever regimen of administration was used; in fatty tissues the sulbactam concentrations ranged from 2.7 to 3.8 microg/g for group 1 and from 1.7 to 4.0 microg/g for group 2, and sulbactam concentrations in the colonic wall were 5.6 +/- 7.7 and 6.8 +/- 3.2 microg/g in groups 1 and 2, respectively (not significant). Again, no influence of the regimen of administration was observed on tissue ampicillin concentrations; in fatty tissues ampicillin concentrations ranged from 4.1 to 5.4 microg/g for group 1 and from 3.2 to 5.8 microg/g for group 2, and sulbactam concentrations in the colonic wall were 7.0 +/- 2.8 and 11.0 +/- 4.7 microg/g for groups 1 and 2, respectively (not significant). In most patients, the concentrations of ampicillin-sulbactam were greater than the MIC at which 50% of isolates are inhibited (MIC50) for Bacteroides fragilis in the fatty tissues. In the colonic wall, for most patients the concentrations of ampicillin-sulbactam were greater than the MIC90 for B. fragilis. No influence of the regimen of administration was observed on the ratio of the two components in the tissues investigated and in sera. In conclusion, a second intraoperative bolus injection or a continuous infusion were equally effective in maintaining sulbactam-ampicillin concentrations in abdominal tissues. The first method of administration can be recommended since it is easier to handle.     

Cardiac output and mixed venous oxygen content measurements by a tracer bolus method: theory

We present a bolus method of inert-gas delivery to the lungs that facilitates application of multiple inert gases and the multiple inert-gas-exchange technique (MIGET) model to noninvasive measurements of cardiac output (CO) and central mixed venous oxygen content Reduction in recirculation error is made possible by 1) replacement of sinusoidal input functions with impulse inputs and 2) replacement of steady-state analyses with transient analyses. Recirculation error reduction increases the inert-gas selection to include common gases without unusually high (and difficult to find) tissue-to-blood partition coefficients for maximizing the systemic filtering efficiency. This paper also presents a practical method for determining the recirculation contributions to inert expired profiles in animals and determining their specific contributions to errors in the calculations of CO and from simulations applied to published ventilation-perfusion ratio (V/Q) profiles. Recirculation errors from common gases were found to be reducible to the order of 5% or less for both CO and whereas simulation studies indicate that measurement bias contributions from recirculation, V/Q mismatch, and the V/Q extraction process can be limited to 15% for subjects with severe V/Q mismatch and high inspired oxygen fraction levels. These studies demonstrate a decreasing influence of V/Q mismatch on parameter extraction bias as the number of inert gases are increased. However, the influence of measurement uncertainty on parameter extraction error limits improvement to six gases.     

Determinants of regional distribution of a bolus inhaled from residual volume

The volume of lung at residual volume (RV) which fails to receive an inhaled tracer bolus (EXV) was quantitated in 13 normals by comparison of a scintigram of the distribution of a tracer bolus inhaled from RV (BORV) with a scintigram at RV of lung equilibrated with the tracer (EQRV). EXV was found in the dependent lung in the erect position in all subjects but also occurred to a lesser degree at the apex in 11 of 13 subjects. Basal EXV ranged from 1 to 7% of TLC, and unlike apical EXV increased with age (r= 0.91, P less than 0.01). EXV in the decubitus position shifted largely to the dependent lung with none remaining in the original erect apical and basal locations, demonstrating that gravity determined EXV location. Nitrous oxide, which is highly diffusible, failed in four subjects to carry the tracer to basal EXV even though perfusion was documented to persist to this area, implying basal EXV airways were closed, not narrowed. In one of the four subjects apical EXV was readily definable. Nitrous oxide carried tracer into this region, implying patent apical EXV airways.     

The pathogenesis of the lesions produced by Eimeria zuernii in calves

The pathogenesis of the lesions caused by Eimeria zuernii in calves is described. The gross lesions and the development and resolution of the microscopic lesions of the large intestine are described in detail. The development of the first asexual generation causes few changes in the lower ileum. The second asexual generation and gametogony of E. zuernii appear to be the pathogenic stages of its development. It is during these stages of the life cycle that epithelium is lost, capillaries are exposed and that hemorrhage into the lumen of the large intestine occurs. Resolution of these lesions takes place in approximately ten days in calves which survivie.     

Pharmacology of Bay g 2821, a long-acting, high-ceiling diuretic

Bay g 2821 is a diuretic, from a new class of chemical substances, with both the efficacy of diuretics with a high-ceiling activity, such as furosemide, bumetanide and ethacrynic acid, and the prolonged duration of action of thiazides. Pharmacological investigations showed that Bay g 2821 was more potent than furosemide in dogs but less potent in rats. Bay g 2821 did not differ from furosemide in excretion of electrolytes. Further studies showed that Bay g 2821 had an antihypertensive effect in dogs, spontaneously hpertensive rats, and in rats with artificially-induced renal hypertension. Other pharmacological studies did not reveal any other significant effects.     

Immunogenic characterization of a tissue culture-derived vaccine that affords partial protection against avian coccidiosis

The immunogenicity of a tissue culture-derived vaccine generated from an Eimeria tenella-infected cell line in a serologically defined bird line, and the ability to confer protection against homologous challenge in young chicks was examined. The cell line, SB-CEV-1/F7, was infected with E. tenella sporozoites and the resulting 72-h postinfection cell-free supernatants were adjuvanted and used to immunize Leghorn chicks homozygous for the B19 haplotype. Peripheral blood and splenic lymphocytes from these immunized birds proliferated in vitro in response to both sporozoite and SB-CEV-1/F7 tissue culture-derived parasite antigens. In addition, splenic immune lymphocytes obtained from birds previously exposed to E. tenella in vivo responded to these tissue culture-derived parasite antigens in vitro. To evaluate the efficacy of the vaccine, B19B19 chicks were vaccinated s.c. with adjuvanted 72-h postinfection cell-free supernatants or an ammonium sulfate precipitate derivative thereof, orally boosted, and then subjected to homologous parasite challenge at 10 d of age. The level of protection (body weight gain, cecal lesions) was assessed 6 d after challenge. Performance results from four battery trials demonstrated that vaccinated birds were significantly protected against weight loss compared to unimmunized, challenged controls. In addition, in two of the four trials, vaccinated birds were significantly protected against lesions. These results provide strong evidence that tissue culture-derived parasite antigens obtained from the E. tenella-infected SB-CEV-1/F7 cell line are immunogenic in birds and can provide partial protection against E. tenella clinical coccidiosis.     

Eimeria maxima: a comparison of two laboratory strains with a fresh isolate

Oocysts of the Weybridge and Houghton strains of Eimeria maxima and a fresh field isolate were similar and measured on average 30-9 X 22-4 mum. The Weybridge strain and the field isolate produced similar pathogenic effects in 6-week-old chickens, high doses causing 50-80% mortality and severe weight loss. The Houghton strain was slightly less pathogenic and few birds died but more oocysts were produced. With each strain, a single dose gave complete immunity to a light challenge with the homologous strain. Two or 3 immunizing doses gave complete immunity to a heavy homologous challenge but were not sufficient to protect against heterologous challenge.     

Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat

This study was designed to assess the morphological effects of a bolus infusion of PEG-hemoglobin on the heart, lung, liver, spleen and kidney of laboratory rats. Of particular interest was the determination of PEG-hemoglobin's potential to form vacuoles in the tissues and whether these were transitory and article specific. One hundred ten female Sprague-Dawley rats were used in this study. The first experiment determined whether vacuole formation was test article specific by infusing either stroma-free bovine hemoglobin, PEG-hemoglobin, bovine serum albumin, PEG-bovine serum albumin or free PEG. The second experiment assessed the transitory nature of vacuolization. In both experiments, unconscious rats received an intravenous top-loading (bolus) injection of test article via the tail vein. Rats were sacrificed at various time points following administration and had their tissues examined for the presence of vacuoles by light microscope morphological examination and iron staining. Formation of vacuoles appeared to be test article specific with only prolonged circulating, high solute test articles producing vacuoles. These vacuoles appeared dose responsive and transitory in nature. The vacuolization found was non-toxic and believed to be due to the known effect of lysosomal overloading following the phagocytosis of vascularly persistent high solute test articles.     

Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy.

This study evaluated mindfulness-based cognitive therapy (MBCT), a group intervention designed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence. Recovered recurrently depressed patients (n?=?145) were randomized to continue with treatment as usual or, in addition, to receive MBCT. Relapse/recurrence to major depression was assessed over a 60-week study period. For patients with 3 or more previous episodes of depression (77% of the sample), MBCT significantly reduced risk of relapse/recurrence. For patients with only 2 previous episodes, MBCT did not reduce relapse/recurrence. MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacokinetics of L-749,345, a long-acting carbapenem antibiotic, in primates

L-749,345 is a carbapenem antibiotic, currently in phase II clinical trials, which possesses a broad antibacterial spectrum and extended half-life. The time courses of levels of the drugs in plasma and urinary recovery were evaluated for L-749,345, imipenem-cilastatin (IPM), and ceftriaxone (CTX) in male rhesus monkeys (Macaca mulatta) and a chimpanzee (Pan troglodytes). The chimpanzee pharmacokinetics was predictive of human results and indicated a compound that was superior to IPM and approached CTX in its ability to persist in the circulation. Levels of binding to protein, in the range of clinically relevant concentrations in serum, are virtually equivalent for L-749,345 and CTX in humans. Results of a crossover bioassay versus those of a high-pressure liquid chromatography assay of 1-g human samples showed that there were no bioactive metabolites of L-749,345. The extended half-life at elimination phase of L-749,345 allows consideration of single daily dosing. In contrast to results with IPM, the improved stability of L-749,345 with respect to hydrolysis by the renal dehydropeptidase I (0.25 times the rate of IPM) results in urinary recovery sufficient for the drug's use as a single agent.     

Quantifying risk factors of coccidiosis in broilers using on-farm data based on a veterinary practice

A study was done to find and quantify risk factors for coccidiosis. The study population consisted of 4774 broiler flocks kept on 177 farms. Flocks were considered a case when at least one bird in the flock showed microscopic presence of oocysts in intestinal scrapings in a grow-out cycle. Other flocks were defined as controls. This was done for three types of Eimeria: Eimeria acervulina, Eimeria tenella and Eimeria maxima. Logistic regression was used to assess variables that influence the occurrence of Eimeria species. There were 49 variables, based on animal, flock or farm level. There was an enhanced risk of coccidiosis due to environmental and management factors that increase the risk of introducing contamination or that are related to hygienic measures. These include lack of use of overalls by visitors, a farmyard which is difficult to clean, bad hygienic status, personnel who might also be working on other farms, presence of other animals on the farm, and feeding and drinking systems which are more difficult to clean. Also, the presence of other diseases on the farm and Eimeria species found in the previous flock increased the risk of coccidiosis.     

Prevention of carotid artery thrombosis by oral platelet GPIIb/IIIa antagonist in dogs

BACKGROUND AND PURPOSE: Current antithrombotic therapy in acute ischemic stroke and myocardial infarction in which a combination of antiplatelet agents (aspirin) and anticoagulants (heparin) was used led to partial reduction of acute thrombotic complications. Recent advances in antiplatelet research led to the discovery of the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), the final common pathway for platelet aggregation. The present study was undertaken to determine the oral antithrombotic efficacy of a potent and specific platelet GPIIb/ IIIa antagonist, DMP728, in an electrically induced carotid artery thrombosis model in dogs. Based on the powerful antiplatelet efficacy of this mechanism in inhibiting all agonist-induced platelet aggregation as well as in inhibiting platelet procoagulant activity (thrombin generation and hence fibrin formation), an orally active antagonist for this integrin receptor might have potential benefits in stroke. METHODS: Anesthetized dogs were instrumented for monitoring of arterial blood pressure, heart rate, and carotid artery flow velocity. Animals were treated with saline or DMP728 (0.1 to 1.0 mg/kg PO). Thrombus formation (platelet-rich aggregate with fibrous coating and a few erythrocytes) by anodal electrolytic stimulation (300 microA) to the intimal surface of the right carotid artery was initiated 120 minutes after oral DMP728 administration and continued for 180 minutes. Whole blood cell counts, ex vivo platelet aggregation, and template bleeding time were determined at different time points throughout the study. RESULTS: DMP728 administered at 0.1 to 1.0 mg/kg PO exhibited dose-dependent antithrombotic efficacy in this model. DMP728 was shown to be significantly effective in inhibiting ex vivo platelet aggregation and in inhibiting thrombosis at 0.3 to 1.0 mg/kg PO. The antiplatelet, antithrombotic effects of DMP728 were demonstrated without any significant changes in the different hemodynamic or coagulation parameters. These data demonstrated the oral antithrombotic efficacy of DMP728 in dogs. CONCLUSIONS: Platelet GPIIb/IIIa blockade with an orally active antagonist was shown to be safe and effective in the prevention of carotid artery occlusive thrombosis.     

Eimeria tenella: cloning and characterization of cDNA encoding a S3a ribosomal protein

We determined the genomic organization of human CRF type-1 receptor (hCRF-R1). The gene coding for hCRF-R1 consists of at least 14 exons and spans over 20 kilobases. hCRF-R1's three reported isoforms originate from the same gene by alternative splicing. The first hCRF-R1, which binds to CRF with the highest affinity and transduces the most sensitive cAMP accumulation in response to CRF, is encoded in a total of 13 exons, the only one excluded being exon 6. The second isoform contains an additional 29-amino acid sequence which corresponds to exon 6. Unlike the first isoform, the third lacks a 40-amino acid sequence, corresponding to exon 3. Exon-intron boundaries are the same as that of the consensus sequence. Locations of introns in the coding sequence are similar to human CRF-R1, rat CRF-R1, human CRF-R2alpha and others belonging to the human glucagon receptor family.     

Metabolism and excretion of dimethoate following ingestion of overtolerance peas and a bolus dose

Data to guide an exposure assessment were obtained by giving sugar peas containing overtolerance dimethoate residues (17 ppm; 8% oxon) and a bolus dose of dimethoate to a healthy adult male. The dimethoate tolerance on peas was and remains 2 ppm. Serial total urine samples were collected and analysed for dimethoate and its oxon, dimethylphosphate, dimethylphosphorothioate (DMTP) and dimethylphosphorodithioate. The dose of dimethoate administered was approx. 0.1 mg/kg body weight and produced no symptoms of toxicity. Dimethylphosphates appeared in the urine within 2 hr. The major metabolite (about 60%) was DMTP. Only traces (< 0.5%) of dimethoate and oxon were recovered from urine. Acetylcholinesterase inhibition was not observed although urinary metabolites were prominent, indicating that they are better indicators of acute exposure than cholinesterase inhibition. The results obtained using a bolus dose were virtually identical to those from the trial with overtolerance peas, and indicated that dimethoate is readily absorbed and its urinary metabolites are readily eliminated following exposures to low doses (0.1 mg/kg body weight).