Assessing the benefits and usefulness of Schwartz Centre rounds in second-year medical students using clinical educator-facilitated group work session: not just "a facilitated moan"!

BACKGROUND: An experiential curriculum exposing medical students to the clinic early has many benefits but comes with the emotional stress this environment engenders. Schwartz rounds (SR) are an effective means to combat emotional stress and increasingly used in UK and USA hospitals. Recent studies show that the SR format may also provide benefits for medical students. This study aimed to investigate whether the guidance of SR in second year medical students provides the same benefits as to healthcare professionals. METHODS: SR assessment involved 83 s year MBChB students in facilitated groupwork sessions. Topics discussed were "change and resilience" and "duty of candour". Students completed a Likert Scale questionnaire evaluating outcomes proffered by the Point of Care Foundation in collaboration with the Schwartz Foundation, with freeform feedback. RESULTS: There was an 86% completion rate with 25% providing written feedback. Participants were more likely to agree than disagree that SR were beneficial. SR effectiveness in enhancing students' working relationship awareness and skills was strongly correlated with understanding the purpose of, and engagement with, the SR (P < 0.001). Similarly, engagement with the SR was strongly correlated with self-reporting of enhanced patient-centredness (P < 0.001). Freeform feedback could be grouped into five themes that revolved around understanding of the SR and engagement with the process. Many positive comments regarded the SR as a forum not only to "learn experientially" but to so in a "safe environment". Many negative comments stemmed from students not seeing any benefits of engagement with the SR, in that sharing experiences was "unbeneficial", "empathy is inherent and not learnt", or that sharing emotional problems is simply "moaning". CONCLUSION: SRs are an effective way of fostering empathy and understanding towards patients and colleagues. However, for the students to benefit fully from the SR it is necessary for them to engage and understand the process. Therefore, for the successful implementation of SR into pre-clinical medical education, it is important to help students realise that SR are not merely a "facilitated whinge".

A prospective study evaluating the integration of a multifaceted evidence-based medicine curriculum into early years in an undergraduate medical school.

BACKGROUND: The importance of ensuring medical students are equipped with the skills to be able to practice evidence-based medicine (EBM) has been increasingly recognized in recent years. However, there is limited information on an effective EBM curriculum for undergraduate medical schools. This study aims to test the feasibility of integrating a multifaceted EBM curriculum in the early years of an undergraduate medical school. This was subsequently evaluated using the validated Fresno test and students' self-reported knowledge and attitudes as they progressed through the curriculum. METHODS: EBM was integrated horizontally and vertically into the curriculum into the first 2 years of undergraduate medical school. First year medical students were recruited to participate in the study. The 212-point Fresno test was administered along with a locally developed questionnaire at baseline before EBM teaching in year one and at the end of EBM teaching in year two. RESULTS: Thirty-one students participated at baseline and 55 students participated at the end of second year EBM teaching. For the 18 students who completed the Fresno at both time points, the average score increased by 38.7 marks (p < 0.001) after EBM teaching. Students felt confident in formulating clinical questions and in critically appraising journal articles after EBM teaching. EBM was perceived to be important to their future practice as a doctor and for improving patient outcomes at both time points. CONCLUSIONS: It has been feasible to integrate a multifaceted, EBM curriculum from the first year of an undergraduate medical program. Early evaluation of the curriculum using the Fresno test has shown a significant increase in students' EBM knowledge. The curriculum also demonstrated an increase in students' perceptions of the clinical relevance of EBM in their developing practice.

Evaluation of inner teat morphology by using high-resolution ultrasound: Changes due to milking and establishment of measurement traits of the distal teat canal.

The teat canal is important in the defense against invading pathogens, but its functional features can be impeded by the milking process. The objective of our study was to compare teat morphology before and after a standard milking procedure using high-resolution ultrasonography. Tissue changes were determined by measuring inner traits of teat morphology: teat width, teat end width, teat cistern width, diameter of the lower and upper teat wall, teat canal length, and teat canal diameter. Additionally, 3 traits describing the distal teat canal and its external orifice were established: diameter of the distal teat canal orifice, distal teat canal perimeter, and distal teat canal surface. In the first trial, we verified the repeatability of scanning over time with a mixed model. During the second trial, significant changes after milking were observed for all measured traits of teat morphology except teat end width. The traits from the distal teat canal and its orifice were remarkably changed by milking: distal teat canal orifice, +28.9%; distal teat canal perimeter, +25.0%; and distal teat canal surface, +41.5%. Comparing multiparous versus primiparous cows, higher values of teat width, teat end width, and teat canal length were observed in the older animals. Testing the effect of milk yield on teat dimensions, cows with milk yields >11.0 kg/afternoon milking were found to have larger teat widths, teat end widths, and cistern widths before attachment of the cluster. Furthermore, we observed associations of inner teat morphology toward bacterial counts in the appropriate milk. Regarding this udder health-related parameter especially, the newly established traits showed a connection. Teats in which milk showed bacterial growth had larger distal teat canal perimeters and distal teat canal surfaces. High-resolution ultrasonographic scanning of dairy teats allowed a detailed visualization of the inner morphology. The applied procedure can therefore serve as a useful tool for comparison and evaluation of different milking techniques by analyzing the resulting changes of the morphological traits. The thorough description of teat tissue can also be applied for drawing conclusions on the status of the teat canal's physical and mechanical defense function.

The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity.

BACKGROUND: Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. Δ(9)-Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia and body weight reduction in lean mice. We investigated its effects in dietary-induced (DIO) and genetically (ob/ob) obese mice. METHODS: We performed two dose-ranging studies in DIO mice; study 1: 0.3, 1, 2.5, 5 and 12.5 mg kg(-1), oral twice daily for 30 days and study 2: 0.1, 0.5, 2.5 and 12.5 mg kg(-1), oral, once daily for 45 days. One pilot (study 3: 0.3 and 3 mg kg(-1), oral, once daily) and one full dose-ranging (study 4: 0.1, 0.5, 2.5 and 12.5 mg kg(-1), oral, once daily) studies in ob/ob mice for 30 days. The CB1 inverse agonist, AM251, oral, 10 mg kg(-1) once daily or 5 mg kg(-1) twice daily was used as the positive control. Cumulative food and water intake, body weight gain, energy expenditure, glucose and insulin levels (fasting or during oral glucose tolerance tests), plasma high-density lipoprotein and total cholesterol, and liver triglycerides were measured. HL-5 hepatocytes or C2C12 myotubes made insulin-resistant with chronic insulin or palmitic acid were treated with 0, 1, 3 and 10 µM THCV or AM251. RESULTS: THCV did not significantly affect food intake or body weight gain in any of the studies, but produced an early and transient increase in energy expenditure. It dose-dependently reduced glucose intolerance in ob/ob mice and improved glucose tolerance and increased insulin sensitivity in DIO mice, without consistently affecting plasma lipids. THCV also restored insulin signalling in insulin-resistant hepatocytes and myotubes. CONCLUSIONS: THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.

Circulating levels of the cytokines IL10, IFNγ and resistin in an obese mouse model of developmental programming.

An infant's early developmental environment plays a pivotal role in the programming of its physiological phenotype. The identification of the factors in the maternal environment that mediate the effects of maternal obesity and diet is essential to the development of clinical intervention strategies. Maternal hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, hyperleptinaemia and altered inflammatory cytokines concentrations are potentially important predictive factors of her future offspring's susceptibility to metabolic disease. Using a diet-induced obese mouse model, we have investigated which of these maternal factors could induce adverse metabolic programming in the offspring. Female C57Bl/6 mice were fed either laboratory chow (10% fat) or high fat diet (42% fat) for 10 weeks before mating and throughout gestation. At day 18 of pregnancy, maternal body weight, body composition and glucose tolerance were measured, as well as plasma insulin, adiponectin, RBP4, leptin, resistin and the inflammatory cytokines (IL6, IL10, IL12, IL1ß, IFNγ, KC, TNF-α). At day 18 of pregnancy, high fat-fed dams were significantly heavier than the chow dams and had increased fat mass. High fat-fed dams had higher 5 h fasting blood glucose than chow dams and elevated plasma insulin. Although the obese dams had both reduced plasma adiponectin and resistin levels compared with lean dams, their plasma IL6, IL10 and IFNγ levels were all increased. High fat feeding in pregnancy leads to altered plasma concentrations of both adipokines and adipocytokines in the dam that may directly pass to the fetus and affect their development.

Leanness in postnatally nutritionally programmed rats is associated with increased sensitivity to leptin and a melanocortin receptor agonist and decreased sensitivity to neuropeptide Y.

BACKGROUND: Pups of normally nourished dams that are cross-fostered after birth to dams fed a low-protein (8% by weight) diet (postnatal low protein (PLP)) grow slower during the suckling period and remain small and lean throughout adulthood. At weaning, they have increased expression in the arcuate nucleus (ARC) of the hypothalamus of the orexigenic neuropeptide Y (NPY) and decreased expression of pro-opiomelanocortin, the precursor of anorexigenic melanocortins. OBJECTIVES AND METHODS: We investigated, using third ventricle administration, whether 3-month-old male PLP rats display altered sensitivity to leptin with respect to food intake, NPY and the melanocortin 3/4-receptor agonist MTII, and using in situ hybridization or laser capture microdissection of the ARC followed by RT-PCR, whether the differences observed were associated with changes in the hypothalamic expression of NPY or the leptin receptor, NPY receptors and melanocortin receptors. RESULTS: PLP rats were smaller and had reduced percentage body fat content and plasma leptin concentration compared with control rats. Leptin (5 µg) reduced food intake over 0-48 h more in PLP than control rats (P<0.05). Submaximal doses of NPY increased the food intake less in PLP rats than in controls, whereas submaximal doses of MTII reduced the food intake more in PLP rats. Maximal responses did not differ between PLP and control rats. Leptin and melanocortin-3 receptor (MC3R) expression were increased in both ARC and ventromedial hypothalamic nuclei in PLP animals compared with the controls. MC4R, NPY Y1R, Y5R and NPY expression were unchanged. CONCLUSION: Postnatal undernourishment results in food intake in adult rats being more sensitive to reduction by leptin and melanocortins, and less sensitive to stimulation by NPY. We propose that this contributes to increased leptin sensitivity and resistance to obesity. Increased expression of ObRb and MC3R may partly explain these findings but other downstream mechanisms must also be involved.

Lung segment geometry study: simulation of largest possible tumours that fit into bronchopulmonary segments.

BACKGROUND: Segmental resection in stage I non-small cell lung cancer (NSCLC) has been well described and is considered to have similar survival rates as lobectomy but with increased rates of local tumour recurrence due to inadequate parenchymal margins. In consequence, today segmentectomy is only performed when the tumour is smaller than 2 cm. METHODS: Three-dimensional reconstructions from 11 thin-slice CT scans of bronchopulmonary segments were generated, and virtual spherical tumours were placed over the segments, respecting all segmental borders. As a next step, virtual parenchymal safety margins of 2 cm and 3 cm were subtracted and the size of the remaining tumour calculated. RESULTS: The maximum tumour diameters with a 30-mm parenchymal safety margin ranged from 26.1 mm in right-sided segments 7 + 8 to 59.8 mm in the left apical segments 1-3. CONCLUSIONS: Using a three-dimensional reconstruction of lung CT scans, we demonstrated that segmentectomy or resection of segmental groups should be feasible with adequate margins, even for larger tumours in selected cases.

A new, highly selective murine peroxisome proliferator-activated receptor δ agonist increases responsiveness to thermogenic stimuli and glucose uptake in skeletal muscle in obese mice.

AIM: We investigated how GW800644, the first pharmacologically selective murine peroxisome proliferator-activated receptor δ (PPARδ) agonist, affects energy balance, glucose homeostasis and fuel utilization by muscle in obese mice. METHODS: Potencies were determined in transactivation assays. Oral glucose tolerance was determined after 14 and 22 days' administration (10 mg/kg body weight, twice daily) to Lep(ob)/Lep(ob) mice. Food intake and energy expenditure were measured during a 26-day experiment, and plasma metabolites and 2-deoxyglucose uptake in vivo at termination. Palmitate oxidation and 2-deoxyglucose uptake by isolated soleus muscles were measured after 14 (in lean and obese mice) and 26 days. RESULTS: GW800644 activated murine PPARδ (EC(50) 2 nM), but caused little to no activation of PPARα or PPARγ up to 10 µM. It did not increase liver weight. GW800644 reduced food intake and body weight in obese mice after 8 days. It did not affect resting energy expenditure, but, compared to pair-fed mice, it increased the response to a ß(3)-adrenoceptor agonist. It improved glucose tolerance. GW800644, but not pair-feeding, reduced plasma glucose, insulin and triglyceride concentrations. It increased 2-deoxyglucose uptake in vivo in adipose tissue, soleus muscle, heart, brain and liver, and doubled 2-deoxyglucose uptake and palmitate oxidation in isolated soleus muscle from obese but not lean mice. CONCLUSIONS: PPARδ agonism reduced food intake and independently elicited metabolic effects that included increased responsiveness to ß(3)-adrenoceptor stimulation, increased glucose utilization and fat oxidation in soleus muscle of Lep(ob)/Lep(ob) but not lean mice and increased glucose utilization in vivo in Lep(ob)/Lep(ob) mice.

[Three-dimensional reconstruction of central lung tumors based on CT data]. / Dreidimensionale Rekonstruktion von zentralen Lungentumoren basierend auf CT-Daten : Erste klinische Erfahrungen First clinical experiences.

BACKGROUND: CT scanning of the lungs is the standard procedure for preoperative evaluation of central lung tumors. The extent of the tumor and infiltration of central lung structures or lung segments are decisive parameters to clarify whether surgery is possible and the extent of resection. With computer-assisted methods for the segmentation of anatomical structures based on CT data (Fraunhofer MeVis, Bremen) an enhanced, three-dimensional selective visualization is now possible. PATIENTS AND METHODS: From August 2007 through June 2009, 22 patients with central lung tumors were treated at the department of thoracic surgery, University of Schleswig-Holstein, campus Lübeck. There were 15 males and 7 females with a mean age of 60.2 years (range 41-74 years), 18 patients had a long history of smoking, while 4 patients had never smoked. Of the patients 20 had a primary lung carcinoma, 1 patient had local recurrent lung cancer after lobectomy and 1 patient had a central lung metastasis from a non-pulmonary primary carcinoma. A multi-slice detector computer tomogram (MSDCT) scan was performed in all cases. All data were three-dimensionally reconstructed and visualized using special computer-aided software (Fraunhofer MeVis, Bremen). Pulmonary lung function tests, computed postoperative lung volume, bronchoscopic findings, general condition of the patients and the three-dimensionally reconstructed CT data were used for an individual risk analysis and surgical planning. RESULTS: According to the risk analysis 14 out of the 22 patients were surgically treated, 7 patients were staged as functionally inoperable and 1 as technically inoperable. A pneumonectomy was performed in 5 cases, a lobectomy/bilobectomy in 4 cases, an extended lobectomy in 3 cases and 1 case each of a wedge resection and a sleeve resection. Of the 14 patients 2 were classified as stage Ia/b, 7 patients as stage IIa/b and 5 patients as stage IIIa. The median length of time spent in hospital was 8.5±33 days and the mortality rate was 0%. The three-dimensional visualization of the tumor and its anatomical relationship to central pulmonary vessels and the airway system was feasible in all cases. The three-dimensional reconstruction was confirmed in all cases by surgical exploration. CONCLUSION: Three-dimensional reconstruction of CT scan data is a new and promising method for preoperative presentation and risk analysis of central lung tumors. The three-dimensional visualization with anatomical reformatting and color-coded segmentation enables the surgeon to make a more precise strategic approach for central lung tumors.

Downregulation of zinc-{alpha}2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-alpha in adipocytes.

Zinc-alpha2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfalpha mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFalpha.

Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and beta2-adrenoceptor mechanisms.

BACKGROUND AND PURPOSE: Picomolar concentrations of the beta3-adrenoceptor agonist BRL37344 stimulate 2-deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via beta2-adrenoceptors. Effects of BRL37344 and beta2-adrenoceptor agonists are compared. EXPERIMENTAL APPROACH: Mouse soleus muscles were incubated with 2-deoxy[1-(14)C]-glucose, [1-(14)C]-palmitate or [2-(14)C]-pyruvate, and BRL37344, beta2-adrenoceptor agonists and selective beta-adrenoceptor antagonists. Formation of 2-deoxy[1-(14)C]-glucose-6-phosphate or (14)CO2 was measured. 2-Deoxy[1-(14)C]-glucose uptake and beta-adrenoceptor mRNA were measured in C2C12 cells. KEY RESULTS: 10 pM BRL37344, 10 pM clenbuterol and 100 pM salbutamol stimulated 2-deoxyglucose uptake in soleus muscle by 33-54%. The effect of BRL37344 was prevented by 1 microM atenolol but not by 300 nM CGP20712A or IC3118551, or 1 microM SR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nM BRL37344 stimulated 2-deoxyglucose uptake, whereas 100 nM clenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only beta2-adrenoceptor mRNA could be detected by RT-PCR. 10 nM BRL37344 and 10 pM clenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2-deoxyglucose uptake and the effect of clenbuterol was not significant. CONCLUSIONS AND IMPLICATIONS: Stimulation of glucose uptake by 10 pM BRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via beta2-adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nM clenbuterol inhibited 2-deoxyglucose uptake.

Improvement of glucose tolerance in Zucker diabetic fatty rats by long-term treatment with the dipeptidyl peptidase inhibitor P32/98: comparison with and combination with rosiglitazone.

AIM: The aim of this study was to investigate the effect of long-term treatment with the dipeptidyl peptidase inhibitor P32/98 and its combination with rosiglitazone on blood glucose control and islet of Langerhans histology in male Zucker diabetic fatty (ZDF) rats, when treatment begins before or after the development of overt diabetes. METHODS: ZDF rats were treated with P32/98 from the age of 9, 12 or 15 weeks. Rosiglitazone maleate was given to a separate group from the age of 13 weeks. P32/98 was given to all of these rosiglitazone-treated rats from 16 weeks of age. Rosiglitazone maleate was also given from 16 weeks of age to half the rats that were given P32/98 from 9 weeks of age. The compounds were given by oral gavage until the rats were 14 weeks old and then in the diet. The experiment was terminated at the age of 20-21 weeks. Blood glucose, plasma insulin and oral glucose tolerance were measured at intervals; islet histology was assessed terminally. RESULTS: P32/98 improved glucose tolerance after both single and multiple doses when treatment started at 9 weeks of age, also after the third week of treatment when treatment began at 12 or 15 weeks of age. P32/98 reduced daytime blood glucose when treatment began at 12 weeks. Treatment with rosiglitazone increased food intake and body weight, and after 2 weeks, reduced daytime blood glucose, water intake and the area under the glucose tolerance curve. A single dose of P32/98 markedly improved glucose tolerance in rosiglitazone-treated rats. When treatment had begun at 9 weeks of age, P32/98 stimulated insulin secretion in some glucose tolerance tests. Neither P32/98 nor rosiglitazone affected pancreatic insulin content, nor did they have clear effects on islet histology. CONCLUSION: P32/98 elicited a sustained improvement in glucose tolerance in both prediabetic and diabetic ZDF rats. The effects of P32/98 on glucose and insulin were similar to those of rosiglitazone, and in contrast to rosiglitazone, P32/98 did not increase food intake or body weight. However, neither compound was especially effective at improving diabetes in ZDF rats when treatment began at 9, 12 or 15 (P32/98) or 13 (rosiglitazone) weeks of age.

Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation.

OBJECTIVES: To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance. DESIGN: Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump from day 14 of gestation and throughout lactation. A further group was fed a normal diet and given saline. After weaning, the offspring of each group were fed on a normal diet until 6 weeks of age and then half of each group was transferred to a high-fat diet until 12 months of age. RESULTS: Plasma leptin levels were raised two-fold on days 16-18 of pregnancy in the leptin-treated dams, but, despite a constant rate of infusion, at parturition they dipped to control levels before rising again. The activity of placental 11beta-HSD2 was reduced by the low-protein diet; this reduction was prevented by treating the dams with leptin. The male offspring of the saline-treated dams gained more weight and had higher plasma leptin levels on the high fat than the chow diet, but the offspring of the leptin-treated dams did not. Fasting blood glucose and intraperitoneal glucose tolerance at 6 and 12 months of age was unaffected by the high-fat diet, but only the offspring of the leptin-treated dams achieved this control without raised insulin levels. CONCLUSIONS: The rate of leptin clearance appears to increase at parturition. The administration of leptin to rats during late pregnancy and lactation makes their male offspring less susceptible to high-fat-diet-induced weight gain and insulin resistance.

[Cholestatic jaundice and pruritus]. / Cholestatischer Ikterus und Pruritus.

The 38 year old male patient was admitted to our clinic with jaundice and invalidating pruritus of unknown origin. The primary evaluation made by the practitioner of the patient and the initial examinations performed in the clinic revealed no diagnosis. In particular, an infectious liver disease could be excluded. Reevaluation of anamnestic data revealed then the in-take of Dianabol, an often used anabolic steroid as the most possible reason for the cholestatic hepatopathy.

Irrelevant response effects improve serial learning in serial reaction time tasks.

Tones were introduced into a serial reaction time (SRT) task to serve as redundant response effects. Experiment 1 showed that the tones improved serial learning with a 10-element stimulus sequence, but only if the tone effects were mapped onto the responses contingently. Experiment 2 demonstrated that switching to noncontingent response-effect mapping increased SRT only when participants had previously adapted to contingent response-effect mapping. In Experiment 3, the beneficial influence of contingent tone effects on serial learning occurred only when there was sufficient time between the response effects and the next imperative stimuli. The results are discussed in terms of the ideomotor principle. It is claimed that an internal representation of the to-be-produced tone effects develops and gains control over the execution of the response sequence.

Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation.

BACKGROUND: Although there is strong evidence that plasma HDL levels correlate inversely with the incidence of coronary artery disease, the precise mechanism(s) for the protective effect of HDLs remains unclear. We recently showed that HDLs inhibit endothelial cell expression of cytokine-induced leukocyte adhesion molecules in vitro. Our study therefore sought to test the hypothesis that elevating the level of circulating HDLs would inhibit endothelial cell activation in vivo. METHODS AND RESULTS: We used a porcine model of inflammation previously established in our laboratory, in which the level of vascular endothelial cell expression of E-selectin in interleukin (IL)-1alpha-induced skin lesions was measured by the uptake of a radiolabeled anti-E-selectin antibody (1.2B6). Porcine plasma HDL levels were elevated by use of a bolus injection of reconstituted discoidal HDL (recHDL). These particles resemble nascent HDL particles in shape and contain apolipoprotein A-I as the sole protein and soybean phosphatidylcholine as the sole phospholipid. We found that recHDLs inhibited the expression of IL-1alpha-induced E-selectin by porcine aortic endothelial cells in vitro, confirming that the inhibitory effect is conserved with synthetic HDLs and demonstrating that the phenomenon is not restricted to human endothelial cells. In vivo, elevating the circulating level of HDLs approximately 2-fold led to significant inhibition of basal and IL-1alpha-induced E-selectin expression by porcine microvascular endothelial cells. CONCLUSIONS: These observations demonstrate the potential anti-inflammatory action of HDLs and provide support for the further investigation of the mechanisms underlying the inhibitory effects of HDLs on endothelial cell activation.

Cloning of porcine intercellular adhesion molecule-1 and characterization of its induction on endothelial cells by cytokines.

BACKGROUND: The transplantation of pig organs into humans requires a detailed knowledge of similarities and differences between the two species in the molecular physiology of host defense mechanisms. We therefore set out to identify porcine intercellular adhesion molecule (ICAM)-1 and to characterize its expression by endothelial cells. METHODS: Porcine ICAM-1 cDNA was isolated from an endothelial cell cDNA library. An anti-pig ICAM-1 monoclonal antibody was generated and used to investigate the regulation by cytokines of ICAM-1 expression by porcine aortic endothelial cells (PAEC), using flow cytometry. RESULTS: We found that porcine ICAM-1 was similar in primary structure to human ICAM-1, with five Ig-like domains. COS-7 cells transfected with porcine ICAM-1 supported beta2 but not alpha4 integrin-dependent adhesion of human T lymphoblasts. There was a low-level surface expression of ICAM-1 on unstimulated PAEC and increased expression after stimulation with tumor necrosis factor (TNF)-alpha. However expression of ICAM-1 seemed to be significantly lower than that of vascular cell adhesion molecule-1, both on unstimulated and TNF-alpha-activated PAEC. Recombinant porcine interferon-gamma weakly stimulated ICAM-1 expression when incubated alone with PAEC but had an inhibitory effect on the increase in ICAM-1 due to TNF-alpha, both at 8 and 24 hr. CONCLUSIONS: Our observations confirm the existence of ICAM-1 in the pig and provide novel insights into how porcine and human endothelial cells differ in terms of adhesion molecule expression and cytokine responsiveness. Such differences are potentially important in interpreting models of inflammation in the pig and also in understanding the process of rejection of porcine xenografts.

Stage-specific production and release of juvenile hormone esterase from the ovary of Diploptera punctata.

Juvenile hormone esterase (JHE) is a catabolic enzyme that specifically degrades juvenile hormone (JH) and has been identified in hemolymph and tissues in both larvae and adults of numerous insect species. This study investigates the presence of JHE in ovaries of the viviparous cockroach, Diploptera punctata, and the in vitro release of JHE from these ovaries during the first gonadotrophic cycle. JHE is released in vitro from maturing basal (most posterior) follicles and from follicle cells isolated from oocytes during the short period of time between spermatophore release and chorion formation. Enzyme release is dependent upon the presence of calcium in the medium. This released ovarian JHE appears to be larger than and to display ionic characteristics that are different from the isolated hemolymph and fat body JHEs. In addition, JHE activity measured in homogenates of whole ovaries and subsequently oviposited basal oocytes increases dramatically following spermatophore release, coincident with a previously described decline in JH titer in the ovary. A likely role for ovarian JHE is the site-specific degradation of JH in and around the oocyte prior to fertilization and embryonic development.