Bioavailability of vitamin D biofortified pork meat: results of an acute human crossover study in healthy adults.

Vitamin D intakes are concerningly low. Food-based strategies are urgently warranted to increase vitamin D intakes and subsequently improve 25-hydroxyvitamin D (25(OH)D) concentrations. This acute randomised three-way crossover study investigated the efficacy of vitamin D biofortified pork derived from pigs exposed to UVB light to increase serum 25(OH)D3 concentrations, compared to a dose-matched vitamin D3 supplement and control pork in adults (n = 14). Blood samples were obtained at baseline and then 1.5, 3, 6, 9 and 24 h postprandially. There was a significant effect of time (p < 0.01) and a significant treatment*time interaction (p < 0.05). UV pork and supplement significantly increased within-group serum 25(OH)D3 concentrations over timepoints (p < 0.05) (max. change 0.9 nmol/L (2.2%) UV pork, 1.5 nmol/L (3.5%) supplement, 0.7 nmol/L (1.9%) control). Vitamin D biofortified pork modestly increased 25(OH)D3 concentrations and produced a similar response pattern as a dose-matched vitamin D supplement, but biofortification protocols should be further optimised to ensure differentiation from standard pork.

Real-world data on eslicarbazepine acetate as add-on to antiepileptic monotherapy.

OBJECTIVE: To assess retention, tolerability, and safety, efficacy and effects on quality of life (QoL) of eslicarbazepine acetate (ESL) add-on treatment over 6 months in a real-world adult population with partial-onset seizures. METHODS: This non-interventional, multicenter, prospective study was performed in eight European countries. Adult patients (n = 247) for whom the physician had decided to initiate ESL as add-on to an existing antiepileptic drug (AED) monotherapy were invited to participate. The study comprised three visits: baseline, and after 3 and 6 months. Data on ESL retention, efficacy, tolerability, safety, and QoL were collected. RESULTS: After 6 months, the retention rate of ESL was 82.2%, and 81.8% of patients reported a reduction of seizure frequency of at least 50%; 39.2% of patients reported seizure freedom at this time. The mean QOLIE-10 score improved from 2.9 (SD ± 0.8) at baseline to 2.1 (SD ± 0.8) after 6 months. 109 adverse events (AEs) were reported in 57 patients (26.0%); the majority were rated as related to ESL by the investigator and led to a discontinuation of ESL in 25 patients (11.4%). Eight patients (3.7%) suffered at least one serious AE. The most frequently reported AEs were dizziness, headache, convulsion, and fatigue. CONCLUSIONS: This study shows that ESL was well tolerated and efficacious as add-on therapy to one baseline AED. The use of ESL in patients less refractory than those included in previous clinical trials led to higher responder and seizure freedom rates. No new safety issues were observed.

Adrenal Hormone and Metabolic Biomarker Responses to 30 min of Intermittent Cycling Exercise in Breast Cancer Survivors.

The aim of this study was to explore the effect of one bout of aerobic exercise on epinephrine, norepinephrine, cortisol, glucose, lactate, and free fatty acid (FFA) responses in breast cancer survivors and healthy controls. 9 female breast cancer survivors and 9 women without a history of cancer completed 30 min of cycle ergometry exercise at 60% of VO2peak. Blood samples were taken pre-exercise, immediately post-exercise, and 2 h post-exercise from which plasma concentrations of study variables were measured. Immediately and 2 h post-exercise, increases were observed in epinephrine (control group only) norepinephrine (both groups), lactate (both groups), and FFA (both groups immediately post-exercise; breast cancer survivor group only at 2 h post-exercise) (p<0.05). Cortisol decreased immediately and 2 h post-exercise in the control group while glucose decreased immediately post-exercise in the breast cancer survivor group (p<0.05). In conclusion, breast cancer survivors appeared to display attenuated epinephrine, cortisol, and lactate responses while displaying larger magnitude changes in glucose and FFA responses compared to controls. These preliminary findings may have implications for the regulation of metabolism during exercise in breast cancer survivors.

[Anticonvulsant add-on therapy with Eslicarbazepine acetate : Results of the EPOS-study in adults in Germany]. / Antikonvulsive Zusatztherapie mit Eslicarbazepinacetat : Ergebnisse der EPOS-Studie bei Erwachsenen in Deutschland.

BACKGROUND: Due to inadequate seizure control achieved with antiepileptic drug (AED) monotherapy and the considerable side effects at high required doses, patients with partial-onset seizures (POS) often require AED combination therapy. Eslicarbazepine acetate (ESL) is licensed as an add-on therapy for POS and has a favorable tolerability profile. OBJECTIVES: To investigate retention, utilization, reported efficacy, safety and tolerability as well as effects on health-related quality of life using ESL as an add-on treatment to an established monotherapy in a real-world adult population with POS in Germany. PATIENTS AND METHODS: A subgroup analysis was performed on the data derived from the German study sites that had participated in an international, non-interventional, open-label study conducted in eight European countries (eslicarbazepine acetate in partial-onset seizures, EPOS). Adult patients with POS whose physician had decided to prescribe add-on treatment with ESL to an established monotherapy were followed over a total period of approximately six months (three visits: baseline and after periods of approximately three and six months). Data collection included patient retention, reported efficacy, safety and tolerability as well as quality of life (QOLIE-10). RESULTS AND DISCUSSION: The subgroup analysis included 104 patients which had been enrolled at 38 German study sites. After 6 months, retention of ESL add-on therapy was 86.5 %, with 44.7 % of patients reporting seizure freedom over the 3 months prior to this visit. The overall tolerability of ESL add-on therapy was favorable: 32 adverse events (AE) were reported in 20 patients (19.2 %), while only two events in two patients were considered serious. No new safety signals were detected.

Improving vitamin D content in pork meat by UVB biofortification.

Vitamin D deficiency is prevalent worldwide and identification of alternative food-based strategies are urgently warranted. In two studies, 12-week old crossbred pigs (Duroc x (Large White x Landrace)) were exposed daily to narrowband UVB radiation for ∼10 weeks or control (no UVB exposure) until slaughter. In Study 1 (n = 48), pigs were exposed to UVB for 2 min and in Study 2 (n = 20), this duration was tripled to 6 min. All pigs were fed the maximum permitted 2000 IU vitamin D3/kg feed. Loin meat was cooked prior to vitamin D LC-MS/MS analysis. In Study 1, pork loin vitamin D3 did not differ between groups. Study 2 provided longer UVB exposure time and resulted in significantly higher loin vitamin D3 (11.97 vs. 6.03 µg/kg), 25(OH)D3 (2.09 vs. 1.65 µg/kg) and total vitamin D activity (22.88 vs. 14.50 µg/kg) concentrations, compared to control (P < 0.05). Pigs remained healthy during both studies and developed no signs of erythema. Biofortification by UVB radiation provides an effective strategy to further safely increase the naturally occurring vitamin D content of pork loin, alongside feed supplementation.

Compensation or displacement of physical activity in middle-school girls: the Trial of Activity for Adolescent Girls.

OBJECTIVE: The 'activitystat' hypothesis suggests that increases in moderate-to-vigorous physical activity (MVPA) are accompanied by a compensatory reduction in light physical activity (LPA) and/or an increase in inactivity to maintain a consistent total physical activity level (TPA). The purpose of this study was to identify the evidence of compensation in middle-school girls. SUBJECTS: Participants were 6916, 8th grade girls from the Trial of Activity for Adolescent Girls (TAAG). DESIGN: Inactivity and physical activity were measured over 6- consecutive days using accelerometry (MTI Actigraph). A within-girl, repeated measures design was used to assess associations between physical activity and inactivity using general linear mixed models. RESULTS: Within a given day, for every one MET-minute more of inactivity, there was 3.18 MET-minutes (95% confidence interval (CI): -3.19, -3.17) less of TPA (activity >2 METS) on the same day. Daily inactivity was also negatively associated with TPA on the following day. Each additional minute of MVPA was associated with 1.85 min less of inactivity on the same day (95% CI: -1.89, -1.82). Daily MVPA was also negatively associated with inactivity the following day. CONCLUSION: Our results, based on 6 days of observational data, were not consistent with the 'activitystat' hypothesis, and instead indicated that physical activity displaced inactivity, at least in the short term. Longer intervention trials are needed, nevertheless our findings support the use of interventions to increase physical activity over discrete periods of time in middle-school girls.

Antibacterial Activity of Four Plant Extracts Extracted from Traditional Chinese Medicinal Plants against Listeria monocytogenes, Escherichia coli, and Salmonella enterica subsp. enterica serovar Enteritidis.

The worldwide ethnobotanical use of four investigated plants indicates antibacterial properties. The aim of this study was to screen and determine significant antibacterial activity of four plant extracts in vitro and in a poultry digest model. Using broth microdilution, the concentrations at which four plant extracts inhibited Listeria monocytogenes, Salmonella enteritidis, and Escherichia coli over 24 hours was determined. Agrimonia pilosa Ledeb, Iris domestica (L.) Goldblatt and Mabb, Anemone chinensis Bunge, and Smilax glabra Roxb all exhibited a minimum inhibitory concentration (MIC) of 62.5mg/L and a minimum bactericidal concentration (MBC) of 500mg/L against one pathogen. A. pilosa Ledeb was the most effective against L. monocytogenes and E. coli with the exception of S. enteritidis, for which A. chinensis Bunge was the most effective. Time-kills of A. pilosa Ledeb and A. chinensis Bunge against L. monocytogenes, E. coli and S. enteritidis incubated in poultry cecum were used to determine bactericidal activity of these plant extracts. A. chinensis Bunge, significantly reduced S. enteritidis by ≥ 99.99% within 6 hours. A. pilosa Ledeb exhibited effective significant bactericidal activity within 4 hours against L. monocytogenes and E. coli. This paper highlights the potential of these plant extracts to control pathogens commonly found in the poultry gastrointestinal tract.

Rationale, design and methods of the HEALTHY study physical education intervention component.

The HEALTHY primary prevention trial was designed to reduce risk factors for type 2 diabetes in middle school students. Middle schools at seven centers across the United States participated in the 3-year study. Half of them were randomized to receive a multi-component intervention. The intervention integrated nutrition, physical education (PE) and behavior changes with a communications strategy of promotional and educational materials and activities. The PE intervention component was developed over a series of pilot studies to maximize student participation and the time (in minutes) spent in moderate-to-vigorous physical activity (MVPA), while meeting state-mandated PE guidelines. The goal of the PE intervention component was to achieve > or =150 min of MVPA in PE classes every 10 school days with the expectation that it would provide a direct effect on adiposity and insulin resistance, subsequently reducing the risk of type 2 diabetes in youth. The PE intervention component curriculum used standard lesson plans to provide a comprehensive approach to middle school PE. Equipment and PE teacher assistants were provided for each school. An expert in PE at each center trained the PE teachers and assistants, monitored delivery of the intervention and provided ongoing feedback and guidance.

Effects of chronic exposure to DDT and TCDD on disease activity in murine systemic lupus erythematosus.

Oestrogens contribute to the female preponderance of autoimmune diseases such as systemic lupus erythematosus (SLE). Environmental xenoestrogens superimposed upon endogenous pituitary-gonadal axis may affect the development of autoimmunity. This study examined the effects of chronic exposure to xenoestrogens -- o,p'-dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on disease activity in the New Zealand Black/New Zealand White F1 hybrid (B/W) mouse model of SLE. Intact female mice had repeatedly received injections of DDT, TCDD or control vehicle since 6 weeks of age. Weight change, albuminuria, mortality, relevant immunological and histological parameters were assessed. DDT exposure markedly increased the incidence of albuminuria and reduced uterine weight but had no measured effects on immunity or mortality in this study. TCDD-exposed mice had significantly lower incidence of albuminuria, serum anti-DNA antibody and total IgG levels, and mortality compared to controls. Also, TCDD group had significantly lower thymic and splenic weights, decreased percentages of CD4(+)CD8(+) thymocytes and splenic CD4(+) T cells, increased percentage of splenic B220(+)sIgM(+) B cells and higher serum interferon gamma concentration. Taken together, DDT exposure appeared to accelerate the development of albuminuria in lupus-prone mice. TCDD was immunosuppressive to murine SLE. Xenoestrogens may have compound- and tissue-specific effects that require further elucidation in future work.

Prolactin and autoimmune disease.

A number of reports have shown that PRL is an immune-stimulating hormone that is capable of stimulating organ-specific inflammatory disease in humans. More recently, hyperprolactinemia has been associated with the active phase of the immune-complex-mediated autoimmune disease, systemic lupus erythematosus. The theory that PRL contributes substantially to disease activity was upheld in the NZB/W mouse model of spontaneous, hormone-sensitive lupus. Implanted pituitary glands resulted in hyperprolactinemia, accelerated proteinuria, high levels of circulating IgG, and premature death. Therapeutic studies with NZB/W mice, as well as anecdotal evidence from a small number of patients, have provided evidence that PRL suppressive therapy may be beneficial in selected cases of autoimmune disease.

Self-reported and accelerometer-measured physical activity by body mass index in US Hispanic/Latino adults: HCHS/SOL.

The association between obesity and physical activity has not been widely examined in an ethnically diverse sample of Hispanic/Latino adults in the US. A cross-sectional analysis of 16,094 Hispanic/Latino adults 18-74 years was conducted from the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Body mass index (BMI) was measured and categorized into normal, overweight, and obese; underweight participants were excluded from analyses. Physical activity was measured using the 16-item Global Physical Activity Questionnaire and by an Actical accelerometer. Minutes/day of physical activity and prevalence of engaging in ≥ 150 moderate-vigorous physical activity (MVPA) minutes/week were estimated by BMI group and sex adjusting for covariates. No adjusted differences were observed in self-reported moderate (MPA), vigorous (VPA), or MVPA across BMI groups. Accelerometry-measured MPA, VPA, and MVPA were significantly higher for the normal weight (females: 18.9, 3.8, 22.6 min/day; males: 28.2, 6.1, 34.3 min/day, respectively) compared to the obese group (females: 15.3, 1.5, 16.8 min/day; males: 23.5, 3.6, 27.1 min/day, respectively). The prevalence of engaging in ≥ 150 MVPA minutes/week using accelerometers was lower compared to the self-reported measures. Efforts are needed to reach the Hispanic/Latino population to increase opportunities for an active lifestyle that could reduce obesity in this population at high risk for metabolic disorders.

Effect of 12-hour infusion of naloxone on mood and cognition in normal male volunteers.

The effects of a 12-hour naloxone infusion on mood, cognition, and plasma cortisol levels were evaluated in eight normal subjects. The dosage used was a 10 mg dose plus 7 mg/hr (total = 94 mg). Naloxone induced a significant rise in serum cortisol and also induced cognitive impairment, as shown by increased choice reaction time, reduced ability to recall the order of letters and numbers, and reduced accuracy of spatial orientation. The rise in cortisol induced by naloxone was significantly correlated with the rise in the Profile of Mood Scale (POMS) score, indicative of dysphoria. Finally, performance on the spatial orientation task was highly negatively correlated with the peak POMS score after naloxone. From these data and previous studies it is concluded that opioid receptors of low sensitivity to naloxone may mediate a common mechanism regulating the pituitary-adrenal axis' mood, and cognitive function during stress. Personality traits may account for the large individual variability reported in previous studies.

Sex hormones in the pathogenesis of systemic lupus erythematosus.

Sex hormones--estrogens, progestins, androgens, and prolactin--have well-documented effects on the development, progression, or severity of systemic lupus erythematosus (SLE). These effects are complex and are confounded by in vitro and in vivo considerations that obscure a simple explanation of the sexual dichotomies in SLE. An overview of available experimental and clinical data suggests that low androgens and abnormalities in the prolactin-gonadal axis are the most consistent hormonal aberrations found in human SLE. Additional studies focusing on interactions of gonadal steroids with prolactin and other pituitary hormones should expand our understanding of the role of sex hormones in the pathogenesis of SLE and strengthen the potential of hormonal immunotherapy.

School-based interventions improve heart health in children with multiple cardiovascular disease risk factors.

OBJECTIVE: To determine the immediate effects of two types of elementary school-based interventions on children with multiple cardiovascular disease (CVD) risk factors. DESIGN: Randomized, controlled field trial. SETTING: Conducted in 18 randomly selected elementary schools across North Carolina. STUDY PARTICIPANTS: Four hundred twenty-two children age 9 +/- 0.8 years with at least two risk factors at baseline: low aerobic power and either high serum cholesterol or obesity. INTERVENTION: Both 8-week interventions consisted of a knowledge and attitude program and an adaptation of physical education. The classroom-based intervention was given by regular teachers to all children in the 3rd and 4th grades. The risk-based intervention was given in small groups only to children with identified risk factors. Children in the control group received usual teaching and physical education. OUTCOME MEASURES: The primary outcome measure was cholesterol; additional measures were blood pressure, body mass index, body fat, eating and activity habits, and health knowledge. RESULTS: Both interventions produced large reductions in cholesterol (-10.1 mg/dL and -11.7 mg/dL) compared with a small drop (-2.3 mg/dL) in the controls. There was a trend for systolic blood pressure to increase less in both intervention groups than in the controls. Both intervention groups had a small reduction in body fat and higher health knowledge than the control group. CONCLUSIONS: Both brief interventions can improve the CVD risk profile of children with multiple risk factors. The classroom-based approach was easier to implement and used fewer resources. This population approach should be considered as one means of early primary prevention of CVD.

Adhesion molecules in autoimmune disease.

Leukocyte activation, circulation, and localization to inflammatory sites are dependent on adherence to molecules on other cells or to extracellular matrix ligands. Adhesion molecule expression and interactions are probably involved in initiation and propagation of autoimmune diseases. Adhesion molecules pertinent to the development of autoimmunity are the subject of this review. Material in this review was generated by a manual and a computerized search of medical literature pertaining to adhesion molecules and specific autoimmune diseases. Topics covered include adhesion molecule classification, regulation of adhesion, and characterization of adhesion receptors in specific autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, Sjögren's syndrome, autoimmune thyroid disease, multiple sclerosis, and diabetes mellitus. Adhesion molecules are classified into selectin, integrin, and immunoglobulin supergene family groups. Increased adhesion molecule expression and avidity changes occurring with cellular activation are the principal methods regulating leukocyte adhesion. Tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN-gamma), and interleukin-1 (IL-1) stimulate adhesion receptor expression on lymphoid and nonlymphoid tissues. Although differences between specific autoimmune diseases exist, key interactions facilitating the development of autoimmune inflammation appear to include L-selectin/P-selectin/E-selectin, lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1), very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1), and alpha 4B7/MadCAM or VCAM-1 adhesion. Administration of anti-adhesion molecule antibodies in experimental animal models of autoimmunity and in a preliminary trial with RA patients has been successful in preventing or reducing autoimmune disease severity. A vast array of adhesive interactions occurs between immunocompetent cells, endothelium, extracellular matrix, and target tissues during the evolution of an autoimmune disease. Further characterization of leukocyte migration patterns and adherence should clarify pathogenic processes in specific autoimmune diseases and identify potential therapeutic targets for their treatment.

Bromocriptine in rheumatic and autoimmune diseases.

BACKGROUND AND OBJECTIVES: Multiple lines of evidence support the concept that the anterior pituitary hormone prolactin has a pathogenic role in rheumatic and autoimmune diseases including, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Reiter's syndrome, psoriatic arthritis, and uveitis. Conversely, the dopaminergic agonist bromocriptine appears to have therapeutic effects through suppression of pituitary prolactin secretion and, perhaps, through actions on peripheral dopamine receptors. This article reviews the experimental and clinical data supporting the therapeutic use of bromocriptine as a nonstandard or adjunctive therapy in rheumatic and autoimmune diseases. METHODS: Data addressing the potential therapeutic role of bromocriptine in rheumatic and autoimmune diseases, as well as frequently associated comorbidities, was accumulated from the author's work, online literature search of the National Library of Medicine, and references from these identified publications. RESULTS: There have been a number of clinical therapeutic trials using 2.5 to 30 mg of bromocriptine per day in a single or divided dose, which have shown efficacy with minimal side effects in the treatment of rheumatic and autoimmune diseases. In RA, bromocriptine administration has induced immunosuppression of several immune parameters and has been associated with improvements in morning stiffness, grip strength, numbers of swollen/painful joints, and the Health Assessment Questionnaire disability index. In two blinded studies, bromocriptine reduced the number of SLE flares and was as effective as hydroxychloroquine in reducing lupus disease activity indices, respectively. In case reports, bromocriptine has been used successfully in the treatment of Reiter's syndrome enthesopathy and psoriatic arthritis. The potential efficacy of bromocriptine in the treatment of uveitis and multiple sclerosis is suggested but remains to be verified. CONCLUSIONS: Double-blind, placebo-controlled studies are limited, but clinical observations and trials support the use of bromocriptine as a nonstandard primary or adjunctive therapy in the treatment of recalcitrant RA, SLE, Reiter's syndrome, and psoriatic arthritis and associated conditions unresponsive to traditional approaches. Additional investigation is needed to verify this conclusion and extend preliminary results. RELEVANCE: In patients with rheumatic and autoimmune diseases, bromocriptine may be a relatively safe and efficacious alternative therapy. Semin Arthritis Rheum 31:21-32.

Hepatitis C virus infection and autoimmunity.

Hepatitis C virus (HCV) infection has been associated with a plethora of immune and autoimmune perturbations. We review serological and clinical autoimmune manifestations associated with HCV infection, discuss treatment regimens for HCV-related autoimmune diseases, and present a framework for understanding HCV-associated autoimmune disease by performing a computerized literature search from which representative articles were used and referenced. The immune response to HCV may include the development of cryoglobulins, rheumatoid factor, antinuclear antibodies (ANA), anticardiolipin, antithyroid, anti-liver/kidney/microsomal antibodies (anti-LKM), as well as HCV/anti-HCV immune complex formation and deposition. HCV infection is a significant cause of mixed essential cryoglobulinemia, which may then be complicated by cryoglobulinemic glomerulonephritis, vasculitis, or neuropathy. It has also been associated with membranous and membranoproliferative glomerulonephritis. Subsets of autoimmune hepatitis patients are infected with HCV and evidence suggests that HCV is a causative agent of antithyroid antibodies and autoimmune thyroid disease. Although cause-and-effect remain to be proved, there are reports of HCV infection preceding or coincident with polyarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and polymyositis/dermatomyositis (PM/DM). HCV-infected patients also have a high incidence of sialoadenitis, and reports of low-grade lymphoproliferative malignancies have emerged. However, HCV is not a major causative factor for most autoimmune diseases. Optimal treatment for HCV-related autoimmune disease remains to be determined. Interferon alpha (IFN alpha) has successfully reduced viremia/transaminitis, cryoglobulins, proteinuria, and nephritis, but recurrent disease manifestations are frequent after discontinuation of therapy. Moreover, IFN alpha may precipitate or exacerbate autoimmune disease symptoms. HCV-related autoimmune disease also has been treated successfully with corticosteroids, azathioprine, and cyclophosphamide, although HCV viremia persists and may worsen.

The role of alpha 4 integrin and intercellular adhesion molecule-1 (ICAM-1) in murine experimental autoimmune thyroiditis.

Mouse-thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg induce a lymphocytic form of experimental autoimmune thyroiditis (EAT) whereas activation of the same cell population with MTg in the presence of anti-interleukin 2 receptor antibody (M7/20) induces a granulomatous form of EAT. The thyroid infiltrate in both lymphocytic and granulomatous EAT includes both CD4+ and CD8+ T cells and CD4+ T cells are the primary effector cells for both forms of EAT. This investigation was undertaken to begin to define the roles of alpha 4 integrin, and intercellular adhesion molecule-1 (ICAM-1) in the migration of CD4+ and CD8+ T cells to the thyroid in EAT. The studies presented here demonstrate the expression of alpha 4 integrin and ICAM-1 on CD4+ and CD8+ T cells infiltrating the thyroid and the expression of vascular cell adhesion molecule (VCAM) and ICAM-1 on thyroid cells of mice with EAT. The effects of anti-alpha 4 and anti-ICAM mAb administration on EAT severity in recipient mice was also determined. Anti-alpha 4 administration reduced or abolished lymphocyte infiltration in the thyroid resulting in reduced severity of both lymphocytic and granulomatous EAT. In contrast, anti-ICAM mAb had little effect on EAT severity. These results suggest that these two adhesion molecules exhibit differential functional roles in the modulation of EAT disease severity and that alpha 4-VCAM interactions may be of particular importance in trafficking of effector cells to the thyroid.

Intrathyroidal cell phenotype in murine lymphocytic and granulomatous experimental autoimmune thyroiditis.

In-vitro mouse thyroglobulin (MTg) activated spleen cells from immunized donor mice can induce experimental autoimmune thyroiditis (EAT) after transfer to recipient mice. The intrathyroidal cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Cells cultured with MTg together with anti-IL2R antibody induce EAT with a granulomatous histopathology in which the thyroid infiltrate contains mononuclear cells (MNC) in addition to PMN's histiocytes, and multinucleated giant cells. Flow cytometric analysis of intrathyroidal MNC infiltrates demonstrated that both CD4+ and CD8+ T cells infiltrate the thyroid in both lymphocytic and granulomatous EAT and that CD8+ T cells outnumber CD4+ T cells. There were usually increased numbers of PMN's in the granulomatous thyroids, but low number of Ig+ and F4/80+ cells (macrophages) in the intrathyroidal infiltrate of both disease types. IL2R and Pgp-1 were expressed on both CD4+ and CD8+ intrathyroidal T cells. The majority of CD8+ cells were ICAM+, LFA-1+, and CD45RB+ whereas only a small percentage of CD4+ intrathyroidal T cells expressed these markers. There were no major differences in intrathyroidal MNC phenotype between lymphocytic and granulomatous EAT. Depletion of CD8+ T cells in recipient mice did not reduce EAT severity and resulted in an increased percentage of intrathyroidal CD4+ T cells expressing IL2R. These results suggest that CD8+ T cells are not functioning as effector cells in lymphocytic or granulomatous EAT.

High-dose naloxone modifies cardiovascular and neuroendocrine function in ambulant subjects.

To determine the role of the opioids in the control of the cardiovascular system in awake ambulatory subjects, eight healthy men were infused with a high dose of naloxone (10 mg bolus plus 7 mg/hr), or saline placebo, for 12 hr. Ambulatory monitoring of blood pressure and heart rate every 10 min indicated no differences between trials for blood pressure (p greater than 0.80), but a significant difference for the maximal heart rate response during stair climbing or 1 km walks (p less than 0.02). Plasma cortisol concentration were increased during the naloxone trials (p less than 0.05), as was total urinary epinephrine and dopamine output (p = 0.005 and less than 0.03, respectively). Plasma FSH and LH concentrations were elevated during naloxone infusion (FSH: p less than 0.02, LH: p less than 0.01), but neither exercise or mental tasks significantly altered their levels (p greater than 0.20). The cardiovascular responses during moderate mental tasks were not affected by naloxone (p greater than 0.05). These results indicate that in the normal ambulatory state the opioid system has a minor role in cardiovascular regulation, as demonstrated by the urinary catecholamines. Its role becomes more evident when considerable stress is imposed.