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The immune response of 42 gastrointestinal and ovarian cancer patients at 1 month after exposure to murine monoclonal antibodies (B72.3 and CC49) reactive with the tumor-associated antigen TAG-72 was studied. The incidence of human anti-mouse antibody response was 89% to B72.3 and 70% to CC49. To evaluate the antiidiotypic immune response, we developed a serological assay based on affinity chromatography to remove the interference due to the presence of TAG-72, antiisotypic, and antiallotypic immunoglobulins in the serum. Seventy-eight percent of patients who received B72.3 developed an antiidiotypic response; in 33% of the patients, this was the only immune response detected. The antiidiotypic immune response after treatment with CC49 was present in 54% of the patients. Twelve percent of the patients who received CC49 developed an antiidiotypic response in the absence of antiisotypic or antiallotypic immune response. The lower immunogenicity of the variable region of CC49 is encouraging when considering the use of chimeric or humanized antibodies derived from the murine monoclonal antibody CC49 in clinical studies.

Creatine supplements have a long history of use for improving muscle performance. While there are a number of studies that document the effects of creatine supplementation on muscle strength and performance, there are relatively few studies examining oral bioavailability. Despite early studies suggesting nearly complete oral absorption of creatine monohydrate, there are a number of reasons to suggest creatine absorption from the gastrointestinal tract is far from complete and that significant improvements in bioavailability can be obtained. This review examines the mechanisms controlling creatine absorption in the intestine and the implications for improving the bioavailability of creatine supplements.

1. TechneScan MAG3 kit [package insert]. St. Louis, Mo: Mallinckrodt Inc; 2000. 2. OctreoScan kit [package insert]. St. Louis, Mo: Mallinckrodt Inc; 2000. 3. Weber DA, Paras P, Harris CC, et al. Initial testing and quality control for radionuclide dose calibrators. Committee on Standardization of Nuclear Medicine Instrumentation, American College of Nuclear Physicians. Nucl Med Commun. 1986;7:555-65. 4. Calhoun JM, Golas DB, Harris SG. Effects of varying geometry on dose calibrator response: cobalt-57 and technetium-99m. J Nucl Med. 1987;28:1478-83. 5. Chu RYL, Simon WE. Quality control testing of dose calibrators. J Nucl Med Technol. 1996;24:124-8. 6. Zimmerman BE, Coursey BM, Cessna JT. Correct use of dose calibrator values. J Nucl Med. 1998;38:575. 7. Dansereau RN, Methe BM. Dose variance associated with calibration and administration of radiopharmaceuticals. Am J Health Syst Pharm. 2001;58:580-4. 8. 10 CFR 35.50 (b) (4). 9. 10 CFR 35.60 (b).

In August 2009, the American Association of Colleges of Pharmacy (AACP) Council of Sections established a Task Force to assess the current status of compounding education at its member institutions and to provide recommendations for future direction. The Task Force conducted a survey in late June 2010 of faculty members enrolled in the AACP Pharmaceutics and Pharmacy Practice sections to gain qualitative information of the current state of compounding education. The survey results were then organized around eight curricular topics for which the Task Force members provided interpretations and recommendations. A final report was sent to the AACP Council of Sections on February 15, 2011. This publication provides the information contained in that final report to the professional community.

The Geothermal Jobs and Economic Development Impact (JEDI) model, developed through the National Renewable Energy Laboratory (NREL), is an Excel-based user-friendly tools that estimates the economic impacts of constructing and operating hydrothermal and Enhanced Geothermal System (EGS) power generation projects at the local level for a range of conventional and renewable energy technologies. The JEDI Model Geothermal User Reference Guide was developed to assist users in using and understanding the model. This guide provides information on the model's underlying methodology, as well as the parameters and references used to develop the cost data utilized in the model. This guide also provides basic instruction on model add-in features, operation of the model, and a discussion of how the results should be interpreted.

Many industries keep log data on maintenance and support. The log data contains information on the problems reported as well as the actions taken to fix the problems. The log data contains a wealth of information useful for future maintenance, as well as product design and inventory management. However, it is always hard to identify parts involved automatically when the number of part types is large and the data are sloppily authored. Boeing’s P-MATCH identifies part names from noisy non-professionally authored log data. In this chapter, the authors use P-MATCH to illustrate how to leverage the combined strength of natural language processing and text mining.

The terms “neoliberal” and “neoclassical” economics are often used interchangeably in contemporary economic jargon. Historically, they have emerged as identifiers of the contextualization of Adam Smith’s classical economic theory within the conditions of the nineteenth and twentieth century. Therefore, there is nothing truly “neo” in economic neoliberalism. By the end of the nineteenth century Smith’s assertion of “the invisible hand” had been stripped of metaphysical implications and had become the impersonal “hand of the markets” capable of “mobilizing even the basest of human instincts such as gluttony, greed, and the desire for wealth and power for the benefit of all.”1

Transmission electron microscopy was used to study the in vitro development of Eimeria tenella in a novel established avian-derived cell line (designated CEV-1/F7) used for antigen production in chicken immunization studies. Sporozoites of E. tenella were inoculated onto cell monolayers and the cells were fixed at 24-h intervals. Large numbers of intracellular sporozoites were seen at 24 h postinoculation (p.i.), and trophozoites were identified at 24-48 h p.i. Immature schizonts, some with budding merozoites, were seen by 48 h p.i. At 72-96 h p.i., immature and mature schizonts and extracellular merozoites were observed. No merozoite invasion occurred, but immature second-generation schizogony was seen in parasitophorous vacuoles of first-generation schizonts. No further development occurred and degeneration of most schizonts was seen by 120-144 h p.i. The results confirmed synchronous development of E. tenella until 48 h p.i., followed by asynchronous development and ultrastructural degeneration with increased incubation time.

Cells were dispersed from cecal tissues of 1- to 2-day-old turkeys using a mixture of collagenase and dispase to enrich for epithelial cells. The initial culture produced from these cells (TCC) appeared to be heterogeneous, but, as the cells were cultured through 25 passages, they assumed a more fibroblastic appearance. Cellular invasion of the TCC by two species of turkey coccidia, Eimeria adenoeides and Eimeria meleagrimitis, was not enhanced, as compared with invasion in turkey kidney cells (TKC), the cell culture system standardly used to study the avian coccidia in vitro. However, early development by one of the species, E. meleagrimitis, was markedly increased in the TCC (Passages 6 through 19) over that in TKC. Thirty to 42% of the parasites that invaded the TCC developed beyond the sporozoite stage, as compared with 5% development in TKC. Mature first-generation schizonts were observed within 24 hr postinoculation in the TCC, but not until 48 hr in the kidney cells. There was no evidence that development of the second generation was initiated in either the TCC or kidney cells.

The U.S. Department of Energy (DOE) Geothermal Technologies Program (GTP) tasked the National Renewable Energy Laboratory (NREL) with conducting the annual geothermal supply curve update. This report documents the approach taken to identify geothermal resources, determine the electrical producing potential of these resources, and estimate the levelized cost of electricity (LCOE), capital costs, and operating and maintenance costs from these geothermal resources at present and future timeframes under various GTP funding levels. Finally, this report discusses the resulting supply curve representation and how improvements can be made to future supply curve updates.

Background The cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has been estimated to have a very low probability; but effects of cofactors that vary in space and time may substantially alter this pattern. Methods To test the effect of individual variation in the HIV infectiousness generated by co-infection, we developed and analyzed a mathematical sexual network model that simulates the behavioral components of a population from Malawi, as well as the dynamics of HIV and the co-infection effect caused by other infectious diseases, including herpes simplex virus type-2, gonorrhea, syphilis and malaria. Results The analysis shows that without the amplification effect caused by co-infection, no epidemic is generated, and HIV prevalence decreases to extinction. But the model indicates that an epidemic can be generated by the amplification effect on HIV transmission caused by co-infection. Conclusion The simulated sexual network demonstrated that a single value for HIV infectivity fails to describe the dynamics of the epidemic. Regardless of the low probability of heterosexual transmission per sexual contact, the inclusion of individual variation generated by transient but repeated increases in HIV viral load associated with co-infections may provide a biological basis for the accelerated spread of HIV in sub-Saharan Africa. Moreover, our work raises the possibility that the natural history of HIV in sub-Saharan Africa cannot be fully understood if individual variation in infectiousness is neglected.

The 8th International Coccidiosis Conference, held on 9--13 July 2001 in Palm Cove, Australia, was a showcase of the latest studies on widely known coccidia, including Eimeria and Toxoplasma in addition to the emerging or re-emerging parasites such as Neospora, Cryptosporidium and Cyclospora. This meeting was staged in conjunction with the Annual Scientific Meeting of the Australian Society for Parasitology.

Class XI myosins are plant specific and responsible for cytoplasmic streaming. Because of the large number of myosin XI genes in angiosperms, it has been difficult to determine their precise role, particularly with respect to tip growth. The moss Physcomitrella patens provides an ideal system to study myosin XI function. P. patens has only two myosin XI genes, and these genes encode proteins that are 94% identical to each other. To determine their role in tip growth, we used RNA interference to specifically silence each myosin XI gene using 5′ untranslated region sequences. We discovered that the two myosin XI genes are functionally redundant, since silencing of either gene does not affect growth or polarity. However, simultaneous silencing of both myosin XIs results in severely stunted plants composed of small rounded cells. Although similar to the phenotype resulting from silencing of other actin-associated proteins, we show that this phenotype is not due to altered actin dynamics. Consistent with a role in tip growth, we show that a functional, full-length fusion of monomeric enhanced green fluorescent protein (mEGFP) to myosin XI accumulates at a subcortical, apical region of actively growing protonemal cells.

Freshly excysted sporozoites (SZ) of the turkey coccidia Eimeria meleagrimitis and Eimeria adenoeides were incubated at 41 C in concentrations of monensin from .01 to 1.0 microgram/mL, washed free of the drug, and either processed for phase, fluorescence, and transmission electron microscopy or inoculated into cultures of turkey kidney cells. Phase microscopy indicated that after 1.5 h incubation in 1.0 micrograms/mL monensin, about 60% of the SZ of E. meleagrimitis had become notably rounded or displayed localized protrusions. These alterations were accompanied by ultrastructural abnormalities (in 90% of the SZ) including vacuoles in the cytoplasm, bulging and separation of plasma membrane layers, and dense bands in the refractile bodies that extended toward the periphery of the refractile body. Similar morphological and ultrastructural changes were observed in over half of the E. adenoeides SZ after 2 h incubation in 1.0 micrograms/mL monensin. Additionally, some specimens contained a pycnotic nucleus that was usually surrounded by a large vacuole. After 4 h incubation, almost all of the SZ displayed some degree of ultrastructural damage. Indirect fluorescent antibody labeling with parasite-specific monoclonal antibodies demonstrated clouds of antigen surrounding the monensin-treated but not the untreated SZ, suggesting an increase in permeability with incubation in monensin. With both E. meleagrimitis and E. adenoeides, the structural changes were reflected in a significant inhibition of cellular invasion. The inhibitory activity of monensin was concentration- and time-dependent in that the greatest inhibition of invasion was observed in SZ incubated for 4 h in 1.0 micrograms/mL of monensin; shorter incubation times or lower concentrations of monensin having less effect.

Formins are present in all eukaryotes and are essential for the creation of actin-based structures responsible for diverse cellular processes. Because multicellular organisms contain large formin gene families, establishing the physiological functions of formin isoforms has been difficult. Using RNAi, we analyzed the function of all 9 formin genes within the moss Physcomitrella patens . We show that plants lacking class II formins (For2) are severely stunted and composed of spherical cells with disrupted actin organization. In contrast, silencing of all other formins results in normal elongated cell morphology and actin organization. Consistent with a role in polarized growth, For2 are apically localized in growing cells. We show that an N-terminal phosphatase tensin (PTEN)-like domain mediates apical localization. The PTEN-like domain is followed by a conserved formin homology (FH)1-FH2 domain, known to promote actin polymerization. To determine whether apical localization of any FH1-FH2 domain mediates polarized growth, we performed domain swapping. We found that only the class II FH1-FH2, in combination with the PTEN-like domain, rescues polarized growth, because it cannot be replaced with a similar domain from a For1. We used in vitro polymerization assays to dissect the functional differences between these FH1-FH2 domains. We found that both the FH1 and the FH2 domains from For2 are required to mediate exceptionally rapid rates of actin filament elongation, much faster than any other known formin. Thus, our data demonstrate that rapid rates of actin elongation are critical for driving the formation of apical filamentous actin necessary for polarized growth.

A hydrothermal flame is a flame that exists in a supercritical aqueous medium and is characterized by steep temperature and density gradients. The overall objective of our project was to increase understanding of heat, mass, and momentum transport processes within hydrothermal flames. Specifically, we planned to study hydrothermal flame characteristics such as flame temperature and stability, and to develop a method for modeling heat and mass transport processes in the hydrothermal flame and supercritical water environments based on experimental observations. With this knowledge, hydrothermal flames can be tailored to the task of destroying aqueous wastes such as chemical and biological warfare agents or municipal sludges, or used to perform thermal spallation and/or fusion of rock surfaces in a deep-borehole environment for rock drilling and excavation. An autoclave reaction system was designed and constructed to create flame jets in water using both methanol and hydrogen as fuel at a pressure of 250 bar. The temperatures of these flames were measured, and attempts were made to use the flames to spall small rock samples. The experimental system was modified to study the centerline temperature decay of supercritical water jets injected at temperatures up to 525 degrees C into ambient temperature water. A device for measuring the heat flux from these jets was designed, constructed, and used to determine the heat transfer coefficients of the jets impinging against a flat surface. Together, these studies indicate that the necessary temperatures and heat fluxes required to induce thermal spallation in rocks can be achieved in a deep borehole. A detailed account of the experiments and results summarized below is available in Thesis Dissertation "Hydrothermal Spallation Drilling and Advanced Energy Conversion for Engineered Geothermal Systems" by Chad Augustine.

The results of a survey of pharmacy department activities for quality assurance in the preparation of sterile drug products in short-term, nonfederal hospitals are reported. A questionnaire was mailed in March and April 1991 to pharmacy directors at hospitals that had indicated in ASHP's 1990 national survey of pharmaceutical services that they had formal quality assurance processes for intravenous admixture preparation. The adjusted gross sample size was 465. The net response rate was 71% (330 usable replies). Nearly all respondents indicated that sterile drug products were prepared extemporaneously in their departments; 61% reported batch preparation of such products. Both pharmacists and pharmacy technicians prepared sterile products. Respondents identified which guidelines were used in developing departmental policies and procedures for sterile product preparation. Specific areas were identified in which educational programs for pharmacists are needed; the most frequently indicated area (85%) was principles of aseptic technique. A majority of respondents used the following means for the orientation and training of personnel who prepare sterile products: aseptic technique lectures or videotapes, on-the-job training, written policies and procedures, and direct observation of technique. Almost all of the respondents (99%) had laminar-airflow hoods in their departments. Three fourths of those respondents indicated that laminar-airflow hoods were located in a limited-access room. Half of the respondents reported that laminar-airflow hoods were located certified every six months and that prefilters were changed monthly. Less than one third sampled environmental areas for microbial contamination. Less than one third of the surveyed hospitals routinely sampled sterile products for microbial contamination or pyrogens. Almost half indicated the absence of policies and procedures for testing chemical purity, drug concentration, sterility, pyrogenicity, or the environment for sterile preparations. Few respondents indicated the use of sterilization techniques other than microbial filtration, which was used by 32% of pharmacies involved in extemporaneous preparation and 16% of those involved in batch preparation. About 90% of the respondents used published references and manufacturers' recommendations to determine expiration dating. This survey revealed that certain quality assurance procedures related to pharmacy-prepared sterile products need major improvement.

The tremendous increase in device density of present day designs is accompanied by a corresponding increase in transistor failures (hard faults), posing a major challenge to current fault tolerant techniques and tools. We propose a novel "design-time" fault-tolerance methodology at architecture/circuit levels to improve the reliability of applications, where it is possible to classify computations into two categories- (i) those which contribute to quality degradation and, (ii) those which result in total system failure. The proposed scheme enhances system reliability by making appropriate trade-offs between area, output quality (signal to noise ratio or mean square error), and fault tolerance. This low-overhead generic methodology is suitable not only for scaled CMOS technologies, but is also applicable to future nanotechnologies (carbon nanotubes etc.) as well, where such defects are expected to be prevalent. We evaluated this technique on a widely used DSP system - Finite Impulse Response (FIR) filters (where minor degradation in quality can be tolerated). Results show that our technique achieves an improvement between 73.4%-450% (in terms of total system failure probability under iso-redundancy) compared to conventional fault tolerance techniques.

The actin cytoskeleton is critical for tip growth in plants. Profilin is the main monomer actin binding protein in plant cells. The moss Physcomitrella patens has three profilin genes, which are monophyletic, suggesting a single ancestor for plant profilins. Here, we used RNA interference (RNAi) to determine the loss-of-function phenotype of profilin. Reduction of profilin leads to a complete loss of tip growth and a partial inhibition of cell division, resulting in plants with small rounded cells and fewer cells. We silenced all profilins by targeting their 3′ untranslated region sequences, enabling complementation analyses by expression of profilin coding sequences. We show that any moss or a lily (Lilium longiflorum) profilin support tip growth. Profilin with a mutation in its actin binding site is unable to rescue profilin RNAi, while a mutation in the poly-l-proline binding site weakly rescues. We show that moss tip growing cells contain a prominent subapical cortical F-actin structure composed of parallel actin cables. Cells lacking profilin lose this structure; instead, their F-actin is disorganized and forms polarized cortical patches. Plants expressing the actin and poly-l-proline binding mutants exhibited similar F-actin disorganization. These results demonstrate that profilin and its binding to actin are essential for tip growth. Additionally, profilin is not needed for formation of F-actin, but profilin and its interactions with actin and poly-l-proline ligands are required to properly organize F-actin.

The effect of conditioned media from cultures of turkey and chicken intestinal cells on cellular invasion by sporozoites of avian Eimeria species was examined in vitro. Media conditioned by the growth of cells from the ceca, mid-intestine (area of the yolk stalk diverticulum), and duodenal loop were examined for their ability to enhance invasion. Conditioned medium from cultures of turkey cecal cells significantly enhanced invasion by the turkey coccidia Eimeria adenoeides, by 2.4-fold, and E. meleagrimitis, by 2.2-fold, as compared with invasion in the presence of control medium. Conditioned medium from mid-intestinal cell cultures enhanced invasion by the two coccidial species by 2.0- and 2.1-fold, respectively. The enhancement occurred with conditioned media from early (1) as well as later (11) passages of cells. This suggests that the enhancing factor was produced by fibroblast-like cells, the predominant cell type at both early and late passages, and not by epithelial-like cells that had disappeared by the first or second passage. Additionally, conditioned media from cultures of chicken cecal and duodenal loop cells significantly enhanced invasion by the turkey cecal coccidium, E. adenoeides, (1.7- and 1.6-fold, respectively). This was less enhancement than was caused by the turkey cell conditioned media. Heat treatment (56 degrees C for 45 min) of conditioned media failed to alter the effect on invasion. Neither the turkey or chicken cecal cell media nor conditioned media from any other chicken intestinal cell cultures enhanced invasion by E. tenella, the chicken cecal coccidium. Although morphologically dissimilar when they were first plated, the gross appearance and growth of the turkey and chicken cells when conditioned media was collected was comparable.

Purpose. The outcomes of pharmacistmanaged diabetes care services in a community health center were studied. Methods. Eligible patients were over age 18 years and had a diagnosis of type 2 diabetes mellitus. Patients were randomly assigned by the clinical pharmacist and nurse to the intervention group ( n = 76) or control group ( n = 73). Patients in the intervention group were enrolled in a pharmacist-managed diabetes care program. Patients in the control group received the standard diabetes care. The primary endpoint was reduction in glycosylated hemoglobin (HbA1c); secondary outcome measures included weight loss, an improved body mass index, decreased blood pressure, and an improved lipid panel. Quality-of-life measures (health level, satisfaction, impact, worry about disease, and worry about social and vocational issues) were also assessed. Results. Demographic differences between groups were not remarkable. Mean HbA1c levels fell significantly ( p < 0.05) from baseline to nine months in both groups. A diff erence of 1.0 was reported between the groups’ HbA1c levels (95% confidence interval, 0.08–1.78; p < 0.05). Satisfaction level improved from 63.7 to 77.4 in the intervention group, which was significant when compared with the control group, whose satisfaction score improved from 57.0 to 63.4 ( p < 0.05). Conclusion. Patients with type 2 diabetes mellitus who received pharmacist-managed diabetes care demonstrated improved HbA1c, systolic blood pressure, and low-density-lipoprotein cholesterol levels and quality-of-life measures and met treatment goals more often than patients receiving standard care.

The specific aim of this project was to form a partnership between a community health center (CHC) to improve access to exercise for low-income patients with type 2 diabetes.Eligible participants were members of the Siouxland Community Health Center (SCHC), 19 years of age or older, with a diagnosis of type 2 diabetes. Patients were medically waived and received an invitation to exercise at the Siouxland YMCA. An exercise coach (pharmacist, registered nurse, or medical assistant) met with each patient and scheduled and conducted exercise visits for participating patients 2 times each week. Patients' baseline clinical variables were taken and assessed quarterly over a 12-month period.This collaboration established an ongoing exercise program with a total of 1297 exercise encounters in a 12-month period. Forty-eight of 130 eligible patients (36.9%) visited the YMCA on at least 1 occasion. Patients were categorized as experimental (56.3%), involved (25%), and regular (18.8%) exercisers. Nine (18.8%) of the 48 patients attended supplementary YMCA exercise encounters. Five (11%) of the 48 patients renewed and purchased a membership at the YMCA and adopted a self-management approach to regular exercise.The creation of a partnership between a community health center and an exercise organization permitted disadvantaged patients with diabetes an affordable exercise program and contributed to improved clinical measurements. The exercise program can be used as a model for other community health centers and health professionals who desire to improve the implementation of an exercise program for patients with diabetes.

An effective method for the enrichment of two cecal species of the avian Eimeria in mixed cultures has been developed. The method involves the transfer of sporozoites of Eimeria tenella and Eimeria adenoeides from their specific site of invasion in a foreign host bird to the natural host, and markedly increases the numbers of the cecal species in relation to the other species in the mixture. Donor turkeys and chickens were inoculated with mixed cultures containing equal numbers of oocysts of the chicken coccidia, E. tenella + Eimeria acervulina, or the turkey coccidia, E. adenoeides + Eimeria meleagrimitis, respectively. After 8 to 24 h, the cecal tissues of the donor birds were scraped into phosphate-buffered saline and transferred, per os, to the natural host. On Day 6 to 7 posttransfer, numerous oocysts of E. tenella and E. adenoeides were found in the ceca of the recipient chickens and turkeys, respectively. In contrast, only occasional oocysts were found in a few birds in other areas of the intestine.

Objectives To provide background information related to the development of the Nuclear Pharmacy Compounding Guidelines, to discuss regulatory complexities related to radiopharmaceutical compounding practice, and to summarize the gaps in the current compounding regulations for radiopharmaceuticals. Data Sources The Guidelines closely follow the provisions of section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the monographs and chapters related to pharmacy compounding in the United States Pharmacopeia (USP), and the recommended guidelines published by the American Society of Health-System Pharmacists. Summary The Food and Drug Administration Modernization Act (FDAMA) of 1997 established parameters under which the compounding of drug products is appropriate and lawful, but these criteria expressly do not apply to radiopharmaceuticals. The Nuclear Pharmacy Compounding Practice Committee, a group of nuclear pharmacists convened by the American Pharmaceutical Association, developed the Nuclear Pharmacy Compounding Guidelines to establish a set of principles and guidelines for good radiopharmaceutical compounding practice. The intent of the new document is to provide guidance on radiopharmaceutical compounding practices that have evolved over the last 2 decades and to place them in an appropriate regulatory framework in accordance with previous enforcement policies and guidelines issued by the U.S. Food and Drug Administration (FDA) regarding the exemption of certain pharmacy practices from enforcement of adulteration, misbranding, and new drug requirements. Conclusion The Nuclear Pharmacy Compounding Guidelines, recently released by APhA, is the first official document that provides realistic and practical compounding guidance for nuclear pharmacists. Even though the United States Court of Appeals for the Ninth Circuit recently ruled section 503A of the FD&C Act to be invalid in its entirety, and the Supreme Court upheld that ruling, the compliance policy guides issued by FDA in March 1992 and revised in May 2002 maintain guiding principles on pharmacy compounding similar to those stated in section 503A of the FD&C Act. The Nuclear Pharmacy Compounding Practice Committee is optimistic that the practical information contained in the Guidelines will assist state boards of pharmacy, FDA, and the United States Pharmacopeial Convention in setting appropriate standards for nuclear pharmacy compounding practice that will ensure the continued availability of high-quality compounded radiopharmaceuticals at reasonable cost.

Sporozoites of avian Eimeria species differed markedly in their ability to invade cells in vitro. Invasion by E. tenella and E. adenoeides was significantly greater in baby hamster kidney (BHK) and chicken cecal cell (CC) cultures than in primary chicken (PCK) or turkey kidney (PTK) cell cultures. Moreover, invasion of BHK cell cultures by E. adenoeides was significantly greater than that of other Eimeria species, and invasion by E. acervulina sporozoites was significantly lower. Monoclonal antibody 1209-C2 (MAb 1209-C2) reacted by immunofluorescent labeling (IFA) with refractile bodies of sporozoites of 5 species of Eimeria and Caryospora bigenetica, but not with sporozoites of Toxoplasma gondii, Hammondia hammondi, or Cryptosporidium parvum, which have no refractile bodies. The MAb also cross-reacted with formalin-fixed BHK, CC, turkey cecal (TC) cells, and PTK. Pretreatment of BHK cells with MAb 1209-C2 significantly reduced invasion of the cells by sporozoites of E. tenella, E. acervulina, E. meleagrimitis, and C. bigenetica, but did not alter invasion by T. gondii, C. parvum, or H. hammondia. Apparently, reactivity of MAB 1209-C2 with the sporozoites was required for inhibition of invasion despite the fact that the inhibition resulted from pre-treatment of the host cell. Conversely, although MAb 1209-C2 also reacted moderately with PTK and TC cells, pre-treatment of these cell cultures with the MAb did not inhibit invasion by either MAB 1209-C2-reactive or -nonreactive parasites. Collectively, the data indicated that refractile body antigens of sporozoites of Eimeria and Caryospora, which are recognized by MAb 1209-C2, may function in cellular invasion, but also suggest that cellular invasion is probably not mediated by interactions between the conserved epitopes in sporozoites and cultured host cells that are recognized by the MAb.

Radioimmunotherapy with anti-CD20 antibodies is a promising treatment approach for relapsed low-grade non-Hodgkin's lymphoma. Under revised Nuclear Regulatory Commission regulations (May 1997), patients may be released following treatment provided the maximum dose to any individual is not likely to exceed 500 mrem. Non-Hodgkin's lymphoma patients have been studied to evaluate radiation exposure to caregivers/family members after outpatient treatment with tositumomab and iodine I 131 tositumomab (Bexxar® therapy). Estimates of total radiation doses to individuals expected to be maximally exposed to patients posttreatment have revealed that the doses should be within revised guidelines. In a University of Nebraska Medical Center study, the predicted total radiation doses (based on patient dose rate at 1 meter) ranged from 95–423 mrem. Family members were provided radiation-monitoring devices to directly monitor radiation exposure. Measured doses ranged from 10–409 mrem. In this and other studies, estimated and measured dose equivalents to maximally exposed individuals were below 500 mrem. Measured doses were, in most instances, lower than those predicted by patientspecific calculations, thus confirming the validity of the calculated dose predictions. Therefore, radioimmunotherapy with tositumomab and iodine I 131 tositumomab can be safely conducted on an outpatient basis.

To teach drug utilization review (DUR) skills to pharmacy students and assess their abilities and confidence before and after training.Profile reviews and online and live drug-utilization-review activities of increasing difficulty were incorporated into the first (P1), second (P2), and third (P3) years of the Pharmacy Skills Training Laboratory sequence in a doctor of pharmacy (PharmD) curriculum.An online survey instrument was administered to gauge how comfortable students were with specific DUR skills before and after the activities. Students' confidence in performing specific DUR skills improved after completing the activities.Profile reviews, as well as online and live medication reviews, gave students numerous opportunities to practice drug utilization review skills throughout the first 3 years of the pharmacy curriculum. Students' confidence in performing specific drug utilization review skills improved after the activities. Students' ability to perform the skills also improved as measured with the developed checklist in section V and VI of the Pharmacy Skills Laboratory sequence.

To assess muscle breakdown during avian coccidiosis, the level of the non-metabolizable amino acid 3-methylhistidine (3MH) was determined in muscle and plasma from turkey poults that received an infection with a field isolate containing a mixture of Eimeria species. The effect of increased levels of parasitism was evaluated at 6 days postinoculation (DPI) in birds receiving 2.5 x 10(4), 1 x 10(5), or 2 x 10(5) oocysts each. The changes in 3MH levels during recovery from acute infection were assessed at 6-29 DPI in animals given 1.9 x 10(5) oocysts per bird. In some experiments, uninoculated birds given the same amount of feed as infected birds (pair fed) were used to determine the impact of feed deprivation on weight loss and 3MH levels. Infected birds had significantly elevated plasma and muscle 3MH at 6 DPI after a single dose of Eimeria oocysts. The plasma and muscle 3MH returned to control levels after 14 DPI. The 3MH levels increased with increased dose of oocysts. Plasma and muscle 3MH levels were well correlated, and an inverse curvilinear relationship between weight gain and plasma 3MH concentrations levels was observed. Plasma and muscle 3MH levels were significantly elevated in pair-fed birds, but 3MH levels in infected birds were increased by 30% over pair-fed birds. The results suggested that muscle breakdown, as assessed by plasma and muscle levels of 3MH, increased during the acute stage of Eimeria infection in turkey poults.

The effects of prior or concurrent administration of Eimeria acervulina on invasion of cultured cells by Eimeria adenoeides sporozoites and possible mechanisms of action were examined. Baby hamster kidney (BHK) cell cultures that were inoculated with E. acervulina sporozoites were significantly more permissive for invasion by E. adenoeides sporozoites than uninoculated cultures. Enhancement of invasion by E. adenoeides did not occur when the two species were inoculated into cultures concurrently, or within 30 h of each other. However, 48 and 72 h after inoculation of BHK cells with E. acervulina, invasion by E. adenoeides sporozoites was significantly greater than invasion in uninoculated cultures. At 96 h postinoculation with E. acervulina, the enhancing effect on invasion was variable. Culture media collected from E. acervulina-inoculated cultures also significantly enhanced invasion by E. adenoeides. Slight changes in proteins of E. acervulina-inoculated versus uninoculated cell cultures were detected by Western blots of biotinylated and nonbiotinylated cells. Biotinylated bands between 10 and 25 kDa increased in the inoculated cultures. In addition, when chicken anti-E. acervulina sporozoite serum was used as a probe, labeling of a 10 kDa antigen increased in the inoculated cultures.

The Nuclear Regulatory Commission (NRC) regulations that govern release of patients administered radioactive material have been revised to include dose-based criteria in addition to the conventional activity-based criteria. A licensee may now release a patient if the total effective dose equivalent to another individual from exposure to the released patient is not likely to exceed 5 mSv (500 mrem). The result of this dose-based release limit is that now many patients given therapeutic amounts of radioactive material no longer require hospitalization. This article presents measured dose data for 26 family members exposed to 22 patients treated for non-Hodgkin's lymphoma with (131)I-anti-B1 antibody after their release according to the new NRC dose-based regulations.The patients received administered activities ranging from 0.94 to 4.77 GBq (25--129 mCi). Family members were provided with radiation monitoring devices (film badges, thermoluminescent or optically stimulated luminescent dosimeters, or electronic digital dosimeters). Radiation safety personnel instructed the family members on the proper wearing and use of the devices. Instruction was also provided on actions recommended to maintain doses to potentially exposed individuals as low as is reasonably achievable.Family members wore the dosimeters for 2--17 d, with the range of measured dose values extending from 0.17 to 4.09 mSv (17--409 mrem). The average dose for infinite time based on dosimeter readings was 32% of the predicted doses projected to be received by the family members using the NRC method provided in regulatory guide 8.39.Therapy with (131)I-anti-B1 antibody can be conducted on an outpatient basis using the established recommended protocol. The patients can be released immediately with confidence that doses to other individuals will be below the 5-mSv (500 mrem) limit.

The site specificity that avian Eimeria sporozoites and, to a more limited degree, other apicomplexan parasites exhibit for invasion in vivo suggests that specific interactions between the sporozoites and the target host cells may mediate the invasion process. Although sporozoite motility and structural and secreted antigens appear to provide the mechanisms for propelling the sporozoite into the host cell,there is a growing body of evidence that the host cell provides characteristics by which the sporozoites recognise and interact with the host cell as a prelude to invasion. Molecules on the surface of cells in the intestinal epithelium, that act as receptor or recognition sites for sporozoite invasion, may be included among these characteristics. The existence of receptor molecules for invasion by apicomplexan parasites was suggested by in vitro studies in which parasite invasion was inhibited in cultured cells that were treated with a variety of substances designed to selectively alter the host cell membrane. These substance included cationic compounds or molecules, enzymes that cleave specific linkages, protease inhibitors, monoclonal antibodies, etc. More specific evidence for the presence of receptors was provided by the binding of parasite antigens to specific host cell surface molecules. Analyses of host cells have implicated 22, 31, and 37 kDa antigens, surface membrane glycoconjugates,conserved epitopes of host cells and sporozoites, etc., but no treatment that perturbs these putative receptors has completely inhibited invasion of the cells by parasites. Regardless of the mechanism,sporozoites of the avian Eimeria also invade the same specific sites in foreign host birds that they invade in the natural host. Thus, site specificity for invasion may be a response to characteristics of the intestine that are shared by a number of hosts rather than to a unique trait of the natural host. Protective immunity elicited against avian Eimeria species is not manifested in a total blockade of parasite invasion. In fact, the effect of immunity on invasion differs according to the eliciting species and depends upon the area of the intestine that is invaded. Immunity produced against caecal species of avian Eimeria, for example Eimeria tenella and Eimeria adenoeides, inhibits subsequent invasion by homologous or heterologous challenge species, regardless of the area of the intestine that the challenge species invade. Conversely, in birds immunised with upper intestinal species, Eimeria acervulina and Eimeria meleagrimitis, invasion by challenge species is not decreased and often is significantly increased.

The effects of prior (immunity) or concurrent administration of Eimeria acervulina or Eimeria tenella on cellular invasion in vivo and in vitro and on growth performance in white leghorn chickens (WLC) were examined. Weight gains of WLC immunized with E. acervulina and challenged with E. tenella were significantly greater than those of nonimmunized chicks challenged with E. tenella (this occurred despite the increased invasion by E. tenella in E. acervulina-immunized chicks that was reported earlier). The weight gains and modest but consistent improvements in intestinal lesion scores, feed conversion ratios, and oocyst shedding in immunized/challenged WLC indicated that E. acervulina conferred a small measure of protection against E. tenella infection that was independent of the effect on invasion. In contrast, immunization of WLC with E. tenella significantly decreased (41%-51%) invasion by E. acervulina as compared with that in nonimmunized WLC but had little effect on chick growth performance. Concurrent inoculation of chicks with E. tenella and E. acervulina had little effect on invasion by E. tenella sporozoites or on subsequent performance of the chicks. In vitro, prior exposure of cultured cells to either of two isolates of E. tenella also caused a significant decrease in invasion by E. acervulina. No gross changes occurred in the culture morphology between the E. tenella-inoculated and noninoculated cultures. Collectively, the data indicate that prior exposure of WLC and cultured cells to single isolates of avian coccidia markedly influenced invasion by other species but had less effect on the growth performance of the birds.

The effect of a monoclonal antibody (1209-C2) elicited against sporozoite refractile-body antigen on invasion of cultured baby hamster kidney cells by avian Eimeria species was examined in vitro. Pretreatment of sporozoites with 1209-C2 for 45 min before inoculation into cultures or simultaneous introduction of sporozoites and 1209-C2 into cultures had no significant effect on invasion. However, pretreatment of cultures for 45 min with 1209-C2 (also with media from other cloned 1209 cell lines) significantly inhibited invasion by sporozoites of Eimeria tenella and E. adenoeides. Pretreatment of cultures with 2 unrelated monoclonal antibodies with the same isotype as 1209-C2 did not inhibit invasion by E. tenella. There was a significant correlation between time of exposure of the cultures to 1209-C2 and invasion (r = -0.80924; p = 0.0001), with inhibition of invasion occurring after 20 min exposure, but not after 10 min. There was also a significant correlation between the titer of 1209-C2 and invasion (r = 0.62291; p = 0.0305). Monoclonal antibody 1209-C2 cross-reacted with epitopes of baby hamster kidney cells by both immunofluorescence and Western blot. The fluorescent labeling of the cells differed according to the fixative that was used. In formalin-fixed cultures labeled with 1209-C2, fluorescent foci were distributed over the entire cell; after methanol fixation, 1209-C2 reacted with only discrete foci in the nucleus. On Western blots of sporozoites, 1209-C2 reacted with antigens having molecular sizes of approximately 8, 17, 23, 30, and 45-60 kDa, and with several minor bands. On baby hamster kidney cells, the antibody reacted primarily with bands of approximately 30, 45-60, and slightly with other bands. The data suggest that interactions among similar molecules in the sporozoites and host cells may play a role in cellular invasion.

The effect of betaine and salinomycin on absorption of methionine and glucose in tissue from the duodenal loops of Eimeria acervulina-infected chicks was determined. Differences in the ultrastructure of the intestinal cells and parasite developmental stages were also examined. With a drug-resistant isolate of E. acervulina, methionine absorption was significantly higher in chicks fed a basal diet supplemented with 0.15% betaine as compared with absorption in chicks fed the unsupplemented basal diet. Addition of 66 ppm salinomycin to the diet containing betaine did not further enhance absorption. Conversely, with a drug-sensitive isolate, methionine absorption was significantly higher in chicks fed a diet supplemented with both betaine and salinomycin than in chicks fed the unsupplemented basal diet. Tissue from chicks fed any of the supplemented diets was usually significantly heavier than that from chicks fed the unsupplemented diet, even when weight gains of the birds were similar. Glucose absorption was similar in all diet groups. Epithelial cells in coccidia-infected and uninfected chicks fed diets supplemented with betaine or betaine plus salinomycin were less electron dense than cells from chicks fed diets that were not supplemented with betaine. Merozoites of E. acervulina in chicks fed diets supplemented with salinomycin had extensive membrane disruption and vacuolization, but the damage was prevented when betaine was added to the diet. Numerous merozoites and intact schizonts were seen in the intestinal lumen of chicks fed the diet containing betaine plus salinomycin.

During the past several years, our laboratory has been investigating the anticoccidial activities of various natural products that have potential use as dietary supplements for coccidiosis control. Sources of fats containing high concentrations of n-3 fatty acids such as menhaden oil and flaxseed oil and flaxseed, when added to starter rations and fed to chicks from one day of age, effectively reduce lesions caused by the caecal parasite Eimeria tenella, but not lesions caused by Eimeria maxima. Our results are consistent with reports of effects of diets high in n-3 fatty acids on other protozoan parasites which suggest that the state of oxidative stress induced by these diets in the cells of both host and parasites is responsible for their parasitic actions. Artemisinin, a naturally occurring (Artemisia annua) endoperoxide and effective antimalarial significantly lowers lesions from E. tenella when given at low levels as a feed additive. The mechanism of its action is also considered to involve induction of oxidative stress. Diets supplemented with 8 p.p.m. gamma-tocopherol (abundant in flaxseeds) or with 1% of the spice tumeric, reduce mid-small intestinal lesion scores and improve weight gains during E. maxima infections. These compounds may exert their anticoccidial activity because they are effective antioxidants. Betaine, a choline analogue found in high concentrations in sugar beets, improves nutrient utilisation by animals under stress. When provided as a dietary supplement at a level of 0.15% it has enhanced the anticoccidial activity of the ionophore, salinomycin. Betaine may act as an osmoprotectant whereby it improves the integrity and function of the infected intestinal mucosa. In in vivo studies, betaine plus salinomycin significantly inhibit invasion of both E. tenella and E. acervulina. However, subsequent development of E. acervulina is inhibited more effectively with this combination treatment than development of E. tenella.

Eimeria gruis and E. reichenowi are common coccidial parasites of a number of crane species. In the present study, monoclonal antibodies (McAbs), elicited against Eimeria spp. of chickens and turkeys, cross-reacted with sporozoites and developmental stages of E. gruis in the tissues of Florida sandhill cranes. These McAbs were used to define the area of the intestine that was invaded by sporozoites of E. gruis and to demonstrate the feasibility of using McAbs to study the early development of E. gruis in the intestines and visceral organs of cranes. At 6 hr postinoculation (PI), E. gruis sporozoites were found primarily from just proximal to Meckle's diverticulum in the jejunum to the ileocecal juncture. Fewer sporozoites were found in the ceca and rectum, and none were found in the duodenum. Most of the sporozoites were in the middle third of the villi and within the lamina propria. At 14 days PI, developmental stages were detected in the ceca, jejunum, liver, and lungs but not in the heart, kidney, or brain. In the ceca and jejunum, the number, location, and maturity of the stages differed markedly.

Objective Brexpiprazole is a serotonin-noradrenaline-dopamine agent that binds with high affinity to multiple serotonin, norepinephrine and dopamine receptors. In particular, Brexpiprazole is a partial agonist at dopamine D2/D3 and 5-HT1A receptors and an antagonist at 5-HT2A and norepinephrine alpha1B receptors. We assessed the efficacy and safety of brexpiprazole versus placebo as adjunctive therapy to anti-depressant therapy (ADT) in subjects with MDD who demonstrated inadequate response to ADT. Methods This trial had 3 phases: a screening phase (7-28 days); a prospective phase (Phase A): 8-week, single-blind placebo plus an investigator-determined, open-label ADT; a randomized phase (Phase B): 6-week, double-blind, adjunctive brexpiprazole (2 mg/day) vs. placebo in patients with an inadequate response to ADT. The primary efficacy endpoint was the change from the end of Phase A (Week 8) to the end of Phase B (Week 14) in MADRS Total Score. The key secondary endpoint was the change in mean SDS score. Other secondary endpoints were mean change in CGI-S, IDS-R, HAMD and HAMA. Results Of 379 randomized patients, completion rates at Week 14 were high (92.9%). Statistically significant improvements in mean MADRS Total score were observed for subjects receiving adjunctive brexpiprazole 2mg/day compared with placebo (p=0.0001) at endpoint. In addition, on all secondary endpoints Brexpiprazole showed a statistically significant advantage over placebo. Commonly reported adverse events in the brexpiprazole group (>5% and more than twice placebo) were weight gain (8.0%), akathisia (7.4%). Conclusions Brexpiprazole was effective and well tolerated as adjunctive treatment for MDD patients with an inadequate response to ADT.

The objective of this work was to develop patient-specific dosimetry for patients with metastatic gastrointestinal tract cancers who received 111In-CC49 IgG for imaging before therapy with 90Y-CC49 IgG.Whole-body imaging of 12 patients, who received 111-185 MBq (3-5 mCi) of 111In-CC49, commenced in2 hr postinfusion and was continued daily for 4-5 days. SPECT data were acquired at 24 and 72 hr to determine the range of 111In-CC49 activity concentrations in tumors and normal organs. Time-activity curves were generated from the image data and scaled from 111In-CC49 to 90Y-CC49 for dosimetric purposes. Absorbed-dose calculations for 90Y-CC49 included the mean and range in tumor and normal organs. Computed 90Y-CC49 activity concentrations were compared with measurements on 10 needle biopsies of normal liver and four tumor biopsies.In 9 of 10 normal liver samples, the range of computed 90Y-CC49 activity concentrations bracketed measured values. This was also the case for 3 of 4 tumor biopsies. Absorbed-dose calculations for 90Y-CC49 were based on patients' images and activities in tissue samples and, hence, were patient-specific.For the radiolabeled antibody preparations used in this study, quantitative imaging of 111In-CC49 provided the data required for 90Y-CC49 dosimetry. The range of activities in patients' SPECT images was determined for a meaningful comparison of measured and computed values. Knowledge of activity distributions in tumors and normal organs was essential for computing mean values and ranges of absorbed dose and provided a more complete description of the absorbed dose from 90Y-CC49 than was possible with planar methods.

The effect of prior or simultaneous administration of Eimeria acervulina on cellular invasion by E. acervulina, E. tenella, or E. adenoeides was examined in vivo and/or in vitro. In chickens immunized with E. acervulina oocysts, invasion by sporozoites from a challenge inoculum of E. acervulina increased slightly over invasion in naive controls, and invasion by sporozoites of E. tenella and E. adenoeides increased by factors of 1.99 and 2.26, respectively, over that in controls. Conversely, simultaneous inoculation of E. acervulina along with E. tenella or E. adenoeides did not have a significant effect on invasion. Cultured baby hamster kidney cells that had been previously inoculated with E. acervulina sporozoites also supported significantly greater (by factors of 1.39 to 2.66) invasion by E. adenoeides sporozoites than did control cultures. The enhancement of invasion in vitro appeared to depend upon either the interval between the inoculation of cells with E. acervulina and E. adenoeides or the interval between the replating of the cells and their inoculation with E. adenoeides. There were no gross changes in the culture morphology between the E. acervulina-inoculated and noninoculated cultures. The data indicate that prior exposure to E. acervulina enhances invasion by other species of avian coccidia and, therefore, may exacerbate the infection produced by these species.

The effect of conditioned media (media aspirated from a variety of cell cultures after 4 d of growth) on cellular invasion by sporozoites of the turkey coccidium, Eimeria adenoeides, was examined. Conditioned medium from turkey kidney cells and baby hamster kidney cells failed to alter invasion. However, conditioned medium from turkey cecal cell cultures produced a significant (P ≤ 0.05), two-fold increase in invasion over control medium in a variety of cell types. Retentates of conditioned medium from the turkey cecal cells that were passed through microconcentrators having molecular mass cutoffs of 50, 100, and 300 kDa similarly enhanced invasion over retentates from control medium. However, retentates from microconcentrators with a cutoff of 1,000 kDa failed to enhance invasion. Pretreatment in conditioned medium, followed by washing of sporozoites prior to inoculation into cultures, did not result in enhanced invasion. Moreover, when the interval between inoculation of sporozoites into cells and fixation of cultures was reduced to less than 3 h, no enhancement of invasion occurred. Conditioned medium from turkey cecal cells that were grown in the presence of 35S-translabel had at least two labeled bands at 150 kDa and > 200 kDa that were absent in conditioned media from turkey kidney and baby hamster kidney cells.

The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration.Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained.To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation.When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

Cashew (Anacardium occidentale L.), belonging to the family Anacardiaceae, is an evergreen tree with a dome-shaped canopy which almost touches the ground (Fig. 1A). According to Ohler (1979), there are few trees as beautiful as a tall cashew tree. The stout branches arise very low on the trunk and some of them trail on the ground. The bark is thick, resinous, and scaly. The wood is yellow, moderately soft, light, having a relative density of 0.50 (Tavares 1959). The leaves are simple, glabrous, obovate, thickly coriaceous, often notched at the apex. The tree normally comes to flowering in 3 to 5 years. The inflorescence is an indeterminate panicle of which 96% of the flowers are staminate (Johnson 1973). Rao and Hassan (1957a) describe two distinct growth flushes and emergence of panicles on shoots during October and January. The flowers are essentially cross-pollinated (Wait and Jamieson 1986). The pollination is totally dependent on insects (Reddi 1992).

Repeated oral inoculation of turkey poults with large doses (1 x 10(6) oocysts) of the chicken coccidia, Eimeria tenella or E. acervulina, failed to prevent weight loss, poor feed conversion, and intestinal pathology in turkeys challenged with the turkey coccidium, E. adenoeides. Invasion by E. tenella in turkeys was significantly greater than invasion by E. adenoeides in chickens; by 24 hr postinoculation (PI), the numbers of E. tenella and E. adenoeides sporozoites in the ceca had decreased markedly as compared with the numbers that initially invaded, and they did not differ significantly from each other. At 24 hr PI, however, transfer of cecal scrapings from chickens or turkeys inoculated with E. adenoeides produced infection in 53% of the recipient turkeys, but transfer of scrapings from either chickens or turkeys inoculated with E. tenella failed to produce infection in 20 attempts with recipient chickens. Cultured chicken peripheral blood monocytes (PBMs) that were inoculated with E. adenoeides sporozoites contained numerous vesicles that were recognized by the refractile body-specific monoclonal antibody 1209; the number of vesicles was markedly decreased in PBM cultures inoculated with gamma-irradiated E. adenoeides sporozoites. Very few vesicles were detected in the cytoplasm of turkey PBMs that contained E. tenella sporozoites, and none were detected in turkey PBMs containing E. adenoeides sporozoites. The survival of infective sporozoites, along with the secretion of refractile body antigen, may be more critical to the development of cross-species immunity than the number of sporozoites that initially invade the foreign host.

Unimmunized chickens, given intraperitoneal injections of Sephadex at the same time that they were inoculated with oocysts of either Eimeria tenella or E. acervulina, had significantly lower lesion scores at 6 days postinoculation (PI) than unimmunized chickens that were injected with saline instead of Sephadex. Despite the difference in lesion scores, there was little effect on weight gain, except in one experiment, in which Sephadex-injected chickens gained significantly more weight than saline-injected chickens. In contrast, in chickens that were immunized by prolonged exposure to sporozoites of E. adenoeides, injection of Sephadex at the time of challenge with E. tenella did not reduce lesion scores or parasite development as compared with the uninjected chickens, and the weight gain of the Sephadex-injected challenged chickens fell to a level significantly lower than that of their saline-injected challenged counterparts. The data indicate that Sephadex injected at the time of oocyst inoculation 1) produces markedly different effects on lesion scores and weight gain in unimmunized and immunized chickens and 2) abrogates sporozoite-elicited immunity against E. tenella challenge.

A cross-reactive monoclonal antibody (mAb), designated 1205, was used to study redistribution, parasitophorous vacuole (PV) incorporation, and in situ antigen production during the intracellular parasite development of Eimeria acervulina and E. tenella. Western-blot analysis of sporozoite preparations showed that the mAb recognized antigenic bands at 55 and 80 kDa. Indirect immunofluorescent antibody (IFA) labeling of sporozoites produced an internal dot pattern. Immunogold electron microscopy (IM) showed labeling of dense granules within sporozoites. The IFA pattern changed to a general-internal label in immature schizonts followed by a surface-tip pattern in mature merozoites both in vitro and in vivo. IM of the asexual stages revealed the same labeling pattern for the in vivo development of both species, and labeling of rhoptries was seen. In vitro, the PV membrane together with amorphous material within the PV was labeled by IFA during schizont development for E. tenella. No IM labeling of either the PV membrane or material within the PV was observed. Sexual stages seen in vivo for both species had the general-internal IFA pattern.