Phosphoenolpyruvate metabolism in Teladorsagia circumcincta: a critical junction between aerobic and anaerobic metabolism.

Nematodes which have adapted to an anaerobic lifestyle in their adult stages oxidise phosphoenolpyruvate (PEP) to oxaloacetate rather than pyruvate as the final product of glycolysis. This adaptation involves selective expression of the enzyme phosphoenolpyruvate carboxykinase (PEPCK), instead of pyruvate kinase (PK). However, such adaptation is not absolute in aerobic nematode species. We have examined the activity and kinetics of PEPCK and PK in larvae (L(3)) and adults of Teladorsagia circumcincta, a parasite known to exhibit oxygen uptake. Results revealed that PK and PEPCK activity existed in both L(3)s and adults. The enzymes had differing affinity for nucleotide diphosphates: while both can utilise GDP, only PK utilised ADP and only PEPCK utilised IDP. In both life cycle stages, enzymes showed similar affinity for PEP. PK activity was predominant in both stages, although activity of this enzyme was lower in adults. When combined, both the activity levels and the enzyme kinetics showed that pyruvate production is probably favoured in both L(3) and adult stages of T. circumcincta and suggest that metabolism of PEP to oxaloacetate is a minor metabolic pathway in this species.

The kinetics and regulation of phosphofructokinase from Teladorsagia circumcincta.

Phosphofructokinase (PFK-1) activity was examined in L(3) and adult Teladorsagia circumcincta, both of which exhibit oxygen consumption. Although activities were higher in the adult stage, the kinetic properties of the enzyme were similar in both life cycle stages. T. circumcincta PFK-1 was subject to allosteric inhibition by high ATP concentration, which increased both the Hill coefficient (from 1.4±0.2 to 1.7±0.2 in L(3)s and 2.0±0.3 to 2.4±0.4 in adults) and the K(½) for fructose 6 phosphate (from 0.35±0.02 to 0.75±0.05mM in L(3)s and 0.40±0.03 to 0.65±0.05mM in adults). The inhibitory effects of high ATP concentration could be reversed by fructose 2,6 bisphosphate and AMP, but glucose 1,6 bisphosphate had no effect on activity. Similarly, phosphoenolpyruvate had no effect on activity, while citrate, isocitrate and malate exerted mild inhibitory effects, but only at concentrations exceeding 2mM. The observed kinetic properties for T. circumcincta PFK-1 were very similar to those reported for purified Ascaris suum PFK-1, though slight differences in sensitivity to ATP concentration suggests there may be subtle variations at the active site. These results are consistent with the conservation of properties of PFK-1 amongst nematode species, despite between species variation in the ability to utilise oxygen.

The design and delivery of a thermally responsive peptide to inhibit S100B-mediated neurodegeneration.

S100B, a glial-secreted protein, is believed to play a major role in neurodegeneration in Alzheimer's disease, Down syndrome, traumatic brain injury, and spinocerebellar ataxia type 1 (SCA1). SCA1 is a trinucleotide repeat disorder in which the expanded polyglutamine mutation in the protein ataxin-1 primarily targets Purkinje cells of the cerebellum. Currently, the exact mechanism of S100B-mediated Purkinje cell damage in SCA1 is not clear. However, here we show that S100B may act via the activation of the receptor for advanced glycation end product (RAGE) signaling pathway, resulting in oxidative stress-mediated injury to mutant ataxin-1-expressing neurons. To combat S100B-mediated neurodegeneration, we have designed a selective thermally responsive S100B inhibitory peptide, Synb1-ELP-TRTK. Our therapeutic polypeptide was developed using three key elements: (1) the elastin-like polypeptide (ELP), a thermally responsive polypeptide, (2) the TRTK12 peptide, a known S100B inhibitory peptide, and (3) a cell-penetrating peptide, Synb1, to enhance intracellular delivery. Binding studies revealed that our peptide, Synb1-ELP-TRTK, interacts with its molecular target S100B and maintains a high S100B binding affinity as comparable with the TRTK12 peptide alone. In addition, in vitro studies revealed that Synb1-ELP-TRTK treatment reduces S100B uptake in SHSY5Y cells. Furthermore, the Synb1-ELP-TRTK peptide decreased S100B-induced oxidative damage to mutant ataxin-1-expressing neurons. To test the delivery capabilities of ELP-based therapeutic peptides to the cerebellum, we treated mice with fluorescently labeled Synb1-ELP and observed that thermal targeting enhanced peptide delivery to the cerebellum. Here, we have laid the framework for thermal-based therapeutic targeting to regions of the brain, particularly the cerebellum. Overall, our data suggest that thermal targeting of ELP-based therapeutic peptides to the cerebellum is a novel treatment strategy for cerebellar neurodegenerative disorders.

The tricarboxylic acid cycle in L3 Teladorsagia circumcincta: metabolism of acetyl CoA to succinyl CoA.

Nematodes, like other species, derive much of the energy for cellular processes from mitochondrial pathways including the TCA cycle. Previously, we have shown L3 Teladorsagia circumcincta consume oxygen and so may utilise a full TCA cycle for aerobic energy metabolism. We have assessed the relative activity levels and substrate affinities of citrate synthase, aconitase, isocitrate dehydrogenase (both NAD+ and NADP+ specific) and α-ketoglutarate dehydrogenase in homogenates of L3 T. circumcincta. All of these enzymes were present in homogenates. Compared with citrate synthase, low levels of enzyme activity and low catalytic efficiency was observed for NAD+ isocitrate dehydrogenase and especially α-ketoglutarate dehydrogenase. Therefore, it is likely that the activity of these to enzymes regulate overall metabolite flow through the TCA cycle, especially when [NAD+] limits enzyme activity. Of the enzymes tested, only citrate synthase had substrate affinities which were markedly different from values obtained from mammalian species. Overall, the results are consistent with the suggestion that a full TCA cycle exists withinL3 T. circumcincta. While there may subtle variations in enzyme properties, particularly for citrate synthase, the control points for the TCA cycle inL3 T. circumcincta are probably similar to those in the tissues of their host species.

Teladorsagia circumcincta: survival of adults in vitro is enhanced by the presence of a mammalian cell line.

Adult Teladorsagia circumcincta survival and motility in vitro was examined in a range of different cell culture media, supplements and gas mixes. Under optimum conditions, worms survived for 14 days, exhibiting high motility for 9 days and egg production for 72 h. Optimum conditions involved co-culture of worms with a HeLa cell line in a supplemented cell medium (CEM) and an atmosphere containing 10% CO(2), 5% O(2) 85% N(2), 65% humidity at 37 degrees C. The incubation medium consisted of Minimum Essential Medium with 10% fetal calf serum, 1% non-essential amino acids, 1% glutamax and 1% penicillin-neomycin-streptomycin cocktail mix. Compared with optimum conditions, incubation in CEM alone, cell conditioned CEM, RPMI alone, Medium 199 alone, reduced CO(2) or O(2), or when cells were replaced with Escherichia coli, both survival and motility were reduced. Optimum conditions for adult T. circumcincta maintenance for culture, anthelmintic testing or generation of excretory/secretory products are described.

Nitrogen excretion by the sheep abomasal parasite Teladorsagia circumcincta.

Excretion of nitrogenous substances by Teladorsagia circumcincta was investigated during incubation of L3 in phosphate buffer for up to 30h and adult worms for 4-6h. Ammonia was the main excretory product, with about 20% urea. For the first 4-6h, ammonia excretion by L3 was temperature dependent, directly proportional to the number of larvae, but independent of the pH or strength of the phosphate buffer. Later, ammonia excretion slowed markedly in L3 and adults and reversed to net uptake in L3 by 30h. An initial external ammonia concentration of 600 microM did not alter the pattern or magnitude of excretion. Re-uptake of ammonia did not occur at extremes of pH or low buffer strength and was slightly reduced at the highest external concentrations. Ammonium transporters and enzymes of glutamate metabolism, including glutamate dehydrogenase, glutamine synthetase and possibly glutamate synthase, are worthy of further investigation as anthelmintic targets.

[Vasospastic angina pectoris following abortion induced by prostaglandin analogue]. / Vasospastisk angina pectoris ved medicinsk provokeret abort med prostaglandinanalog.

A case of vasospastic angina pectoris with loss of consciousness, bradycardia and seizures induced by medical abortion following administration of mifepristone and gemeprost is reported. The patient had a history of smoking and migraine, and former treatment with ergot alkaloids or serotonin agonists had also resulted in chest pain and lipothymia. The case underlines the importance of obtaining a detailed history of vasospastic disorders in women referred for medical abortion.

Internet course on total quality management.

The Internet provides new opportunities to information-based industries such as universities. If a vast majority of potential customers of our programs have access to the Internet, then it is conceivable that many universities will begin teaching Internet courses and that such courses could, in many cases, replace or at least augment existing face-to-face classroom activities. This paper is an account of one such course at Cleveland State University and the type of policy issues raised by the course at this institution.

Treatment of mandibular angle fractures using one noncompression miniplate.

PURPOSE: This study evaluated the results in patients treated for fractures of the mandibular angle with a single miniplate. PATIENTS AND METHODS: Eighty-one patients with fractures of the mandibular angle were treated by open reduction and internal fixation using one noncompression miniplate with 2.0-mm self-threading screws placed through a transoral incision. No patient was placed into postsurgical maxillomandibular fixation. They were prospectively studied for complications. RESULTS: Thirteen patients with angle fractures (16%) experienced complications requiring secondary surgical intervention. Most of the complications (n = 11), however, were minor and could be treated in the office. Most commonly, intraoral incision and drainage and later removal of the bone plate were required. All patients with minor complications had clinical union. Only two complications required hospitalization for intravenous antibiotics and further surgery. One of these patients had a fibrous union requiring a bone graft. CONCLUSIONS: The use of a single miniplate for fractures of the angle of the mandible is a simple, reliable technique with a relatively small number of major complications.

Female circumcision: a report of four adolescents.

PIP: Although female circumcision is not traditionally performed in the US, health professionals must consider the possibility when seeing a female patient from central Africa that she may have been circumcised. A genital examination should therefore be part of such women's routine health maintenance. Pertinent genitourinary symptoms which may be secondary to the circumcision should be elicited. When pelvic exam is difficult or impossible in a patient, pelvic sonography can supplement rectal exam when pelvic pathology is suspected. Some adolescents may desire reconstructive surgery, while others will want only symptomatic treatment if complications arise. It is also important to create a comfortable environment in which relevant psychosocial issues may be discussed as the young women become acculturated into Western society. Four cases of recently immigrated, circumcised adolescent females from Somalia are reported. It is not illegal to perform female circumcision in the US, but efforts are being made to create and implement such legislation. When parents present requesting a circumcision for their daughter, they must be given information about the risks and complications of the procedure and its outcome. Culturally sensitive counseling should be offered to help the family make its decision.^ieng

Rating journals in health care administration. The perceptions of program chairpersons.

The perceived quality of a journal is often a heavily weighted factor in the appraisal of faculty performance. We developed a listing of 53 prominent journals in the field of health care administration and surveyed the chairpersons of the 52 accredited graduate programs in the United States, Canada, and Puerto Rico, asking each to rate the level of achievement of a faculty member who published in each journal. Using the chi-square goodness-of-fit method for a multinomial experiment, we were able to identify six distinct "tiers" of journals and show a relationship between the subject category of a journal and its tier ranking. The implications of the study findings for faculty members are addressed, followed by a discussion of the data limitations and suggestions for future research.

Evaluation of health care service diversification options in health care institutions and programs by portfolio analysis: a marketing approach.

Originally conceived as a technique to assess how well current activities contribute to the attainment of organizational goals, portfolio analysis also can be used as a marketing research tool for considering the relative merits of various diversification options under consideration by institutional decision makers. The authors describe the features of portfolio analysis and its use as a tool in the evaluation of health care diversification options. A case study of a hospital that has employed the method in its corporate planning and marketing efforts illustrates the use of this analysis technique.

Biological Invasion by Myrica faya Alters Ecosystem Development in Hawaii.

The exotic nitrogen-fixing tree Myrica faya invades young volcanic sites where the growth of native plants is limited by a lack of nitrogen. Myrica quadruples the amount of nitrogen entering certain sites and increases the overall biological availability of nitrogen, thereby altering the nature of ecosystem development after volcanic eruptions.

Integrating knowledge and behavior: development of a management and career development program for graduate health administration education.

How best to integrate cognitive learning and behavioral skills in health administration education has been a concern of both academics and practitioners for many years. Charged with the education of health care administrators, graduate programs are expected to produce persons who are both knowledgeable about the field in which they plan to be employed and skilled in carrying out the many tasks associated with successful performance in their future roles. This article describes the theoretical basis and design of the management and career development offering (MCDO) of Widener University's Graduate Program in Health and Medical Services Administration, the key objectives of which are to integrate cognitive learning with practical experience and to provide a mechanism for the development of needed professional skills in a low-risk academic atmosphere. It was clear that these objectives could not be achieved entirely within a traditional academic curriculum, nor were they always appropriately treated there. However, the complexity of the health care field, the growing demands placed on administrators, and conflicts arising within and between roles increase the necessity to integrate these theoretical and behavioral skills.

Psychosocial determinants of breast self-examination.

To explore the psychosocial determinants of breast self-examination (BSE) among women, we studied a stratified random sample of 264 women students, faculty, and staff in a university community. The dependent variable of the study was self-reported frequency of BSE, and predictors included measures of general health predispositions, variables of the Health Belief Model, the impact of a woman's social network, a set of secondary non-health-related barriers and benefits, and the woman's evaluation of her personal health care system. Analysis of the data showed strong relationships between most of the predictor variables and BSE. Regression analysis showed that variables measuring a woman's recent experience in the health care system were stronger predictors of BSE practice than intrapersonal "health belief" variables. However, the independent variables included in the regression accounted for almost 35 percent of the total variance in BSE practice.

Strategic marketing applications of conjoint analysis: an HMO perspective.

The purpose of this article is to demonstrate how data from a conjoint analysis study can be used to help determine the most appropriate marketing mix for an operational HMO which is entering a new market--the geriatric population. Included are two features which are absent in previous articles on health care applications of conjoint analysis: external validation of results, and a demonstration of how conjoint analysis can be used to simulate market responses to changes in the provider's marketing mix.

Measuring consumer preferences for ambulatory medical care arrangements.

This paper describes how conjoint analysis can be applied to health care marketing. Data from a sample of 73 university students were used to estimate part-worth values for different levels of attributes of ambulatory care arrangements. A high degree of comparative validity was found.