Infection of immunodeficient horses with Sarcocystis neurona does not result in neurologic disease

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.     

Insulin infusion protocol for critical care units.

PURPOSE: An insulin infusion protocol for critical care units is described. SUMMARY: Evidence that aggressive glycemic control improves outcomes led physicians, nurses, dietitians, and pharmacists at a trauma center to develop an insulin infusion protocol. Before the protocol, elevated blood glucose concentrations were often not treated until they reached 200 mg/dL or higher. Insulin infusions were underutilized and were often not started until capillary blood glucose concentrations were greater than 350 mg/dL for 12 or more hours. When orders for an insulin infusion were written, they did not include directions for dosage adjustment, and the goal blood glucose range varied. A preliminary protocol was drafted allowing adjustments in insulin administration to be based on changes in capillary blood glucose values since the previous blood glucose measurement. The protocol was presented to a multidisciplinary team and further refined. The targeted blood glucose concentration range was 80-130 mg/dL. After the targeted range was achieved for a patient, if the blood glucose level continued to decrease over three consecutive measurements, the infusion rate was decreased by 0.5 or 1 unit/hr, depending on the capillary blood glucose level. Data for the first 30 patients were collected from September 2003 to August 2004. It took 2-36 hours (mean, 12.6 hours) to bring the capillary blood glucose concentration to less than 130 mg/dL. Among 2,845 capillary blood glucose measurements, there were 15 cases of hypoglycemia (0.4%) requiring treatment with 50% dextrose injection. CONCLUSION: A multidisciplinary effort resulted in the development of an insulin infusion protocol for use in critical care units.     

Supplementation with macular carotenoids reduces psychological stress,serum cortisol,and sub-optimal symptoms of physical and emotional health in young adults

Purpose: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit.

Methods: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13?mg, or 27?mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire.

Results: Significant baseline correlations were found between MPOD and Beck anxiety scores (r?=??0.28; P?=?0.032), MPOD and Brief Symptom Inventory scores (r?=?0.27; P?=?0.037), and serum cortisol and psychological stress scores (r?=?0.46; P?P?Conclusions: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.     

Long-term collection and characterization of afferent lymph from the ovine small intestine

Reliable methods for long-term collection of afferent lymph draining from the small intestine of sheep are described and validated. The procedure was used successfully in normal sheep, in animals infected experimentally with the parasitic intestinal nematode Trichostrongylus colubriformis and in animals infected naturally with Mycobacterium avium subsp. paratuberculosis, the causative agent of Johne's disease. Our approach enabled afferent lymph draining from the small intestine to be collected continuously for up to 4 months, without any detrimental effects on the animals. Based on cytokine gene expression profiles of afferent intestinal lymph cells, the two infections induced contrasting regional immune responses, namely, Th2-type immunity in the case of T. colubriformis infection and Th1-type immunity in natural cases of Johne's disease. Some immune parameters differed markedly between the two disease models, highlighting the potential value of this approach to gain real-time insights into distinctive host-pathogen interactions as they occur in vivo within the regional immune system of the gastrointestinal tract.     

Pressure Ulcer Prevalence and Incidence in a Rehabilitation Hospital

Pressure ulcers remain a serious health problem, especially in terms of personal suffering and economics. The study described here, conducted in a rehabilitation setting, investigated the prevalence (number of persons with pressure ulcers at a given time) and the incidence (number of persons developing pressure ulcers over a given time) of pressure ulcers. Skin assessments and risk assessments of the subjects were completed using the Braden Scale for Predicting Pressure Sore Risk. Demographic data were obtained. The prevalence rate was 25%, although there was no incidence during the time of this study. Factors associated with the prevalence of pressure ulcers are discussed.     

Infection of Immunodeficient Horses with Sarcocystis neurona Does Not Result in Neurologic Disease

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 × 10⁵ sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 × 10⁸ merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.     

The Cain and Abl of epithelial-mesenchymal transition and transforming growth factor-β in mammary epithelial cells

Transforming growth factor-β (TGF-β) normally inhibits breast cancer development by preventing mammary epithelial cell (MEC) proliferation, by inducing MEC apoptosis, and by creating cell microenvironments that maintain MEC homeostasis and prevent their uncontrolled growth and motility. Mammary tumorigenesis elicits dramatic alterations in MEC architecture and microenvironment integrity, which collectively counteract the tumor-suppressing activities of TGF-β and enable its stimulation of breast cancer invasion and metastasis. How malignant MECs overcome the cytostatic actions imposed by normal microenvironments and TGF-β, and how abnormal microenvironments conspire with TGF-β to stimulate the development and progression of mammary tumors remains largely undefined. These knowledge gaps have prevented science and medicine from implementing treatments effective in simultaneously targeting abnormal cellular microenvironments, and in antagonizing the oncogenic activities of TGF-β in developing and progressing breast cancers. c-Abl is a ubiquitously expressed nonreceptor protein tyrosine kinase that essentially oversees all aspects of cell physiology, including the regulation of cell proliferation, migration and adhesion, as well as that of cell survival. Thus, the biological functions of c-Abl are highly reminiscent of those attributed to TGF-β, including the ability to function as either a suppressor or promoter of tumorigenesis. Interestingly, while dysregulated Abl activity clearly promotes tumorigenesis in hematopoietic cells, an analogous role for c-Abl in regulating solid tumor development, including those of the breast, remains controversial. Here, we review the functions of c-Abl in regulating breast cancer development and progression, and in alleviating the oncogenic activities of TGF-β and its stimulation of epithelial-mesenchymal transition during mammary tumorigenesis.     

Contingency management treatments: Reinforcing abstinence versus adherence with goal-related activities

Contingency management (CM) interventions usually reinforce submission of drug-negative specimens, but they can also reinforce adherence with goal-related activities. This study compared the efficacy of the 2 approaches. Substance-abusing outpatients (N = 131) were randomly assigned to 1 of 3 12-week treatments: standard treatment (ST), ST with CM for submitting negative urine toxicology screens, or ST with CM for completing goal-related activities. CM patients remained in treatment longer and achieved more abstinence than ST patients, but the CM condition that reinforced submission of negative samples resulted in better outcomes than the CM condition that reinforced goal-related activities. Abstinence at 6- and 9-month follow-ups did not differ by group, but longest duration of abstinence achieved during treatment was associated with abstinence posttreatment.