Ep Levels Research Articles

Exposure to biocides and their potential exposure sources among adults: A nationwide population-based study in South Korea

Biocides are present in personal care (including preservatives or antibacterials), pest control, and disinfectant products (including non-agricultural insecticides, fungicides, and disinfectants), and their long-term exposure may induce adverse health effects in humans. Therefore, in this study, we assessed the exposure levels and major exposure predictors of biocides among nationally representative Korean adults. The target group included adults (≥19 years) participating in the Korean National Environmental Health Survey (KoNEHS) 2015–2020. We employed survey-weighted multiple regression analysis and conditional inference trees analysis to assess the associations between demographic characteristics, behavioral sources (including personal care product use, pesticide use, and dietary patterns), and urinary levels of phenol (triclosan [TCS]), parabens (methyl paraben [MP], ethyl paraben [EP], propyl paraben [PP], and butyl paraben [BP]), and the pyrethroid insecticide metabolite (3-phenoxybenzoic acid [3-PBA]). Urinary EP, BP, and 3-PBA levels were higher in South Korean adults compared with those in Western countries. Major exposure predictors for MP, EP, and PP included the use of personal care products such as sunscreen, makeup, and hair care products in KoNEHS 2018–2020. Major exposure predictors for TCS and BP were vegetable consumption, and those for 3-PBA were mosquitocide use during summer in KoNEHS 2018–2020. However, these predictors were not observed in KoNEHS 2015–2017. Collectively, our findings suggest that biocide exposure predictors vary according to changes in product use and diet habits of individuals. Therefore, developing strategies to mitigate biocide exposure based on the demographic and behavioral characteristics of the general population is imperative.

Early diagnostic value of carotid artery ultrasound parameters combined with epicardial adipose layer thickness in coronary heart disease

BACKGROUND Coronary heart disease is associated with coronary atherosclerosis indicated by carotid intima-media thickness (CIMT) thickening and altered vascular elasticity. The epicardial adipose layer can secrete proinflammatory factors that promote the formation of coronary atherosclerosis. Thus, the epicardial fat layer thickness (EAT) may also predict coronary heart disease. AIM To determine the role of common carotid artery ultrasound parameters and EAT in the early diagnosis of coronary artery disease. METHODS Based on coronary angiography, patients with newly suspected coronary heart disease were divided into case (n = 107) and control (n = 41) groups. The carotid ultrasound parameters, including vascular stiffness (β), elastic coefficient (EP), pulse wave conduction velocity (PWV-β), CIMT, and EAT were compared between the case and control groups and among patients with different lesion numbers in the case group. Pearson correlation was used to evaluate the early diagnostic value of EAT, common carotid artery elasticity, and CIMT for coronary heart disease. RESULTS EP, β, PWV-β, CIMT, and EAT were significantly higher in the case group compared with the levels in the control group (all P < 0.001). In the case group, lesions were detected in one vessel in 34 patients, two vessels in 38 patients, and three vessels in 35 patients. Within the case group, β, EP, PWV-β, CIMT, and EAT levels significantly increased with an increased number of lesions (all P < 0.001). EAT positively correlated with β, EP, PWV-β, and CIMT (all P < 0.01). The area under the curve for diagnosing coronary heart disease using EAT combined with CIMT and carotid elasticity was 0.893, and the sensitivity and specificity were 0.890 and 0.837. CONCLUSION EAT correlated well with changes in carotid artery elasticity and CIMT in patients with coronary heart disease. The combination of EAT, carotid artery elasticity, and CIMT facilitates the early diagnosis of coronary heart disease.

PSIII-20 Impact of EnduraPig on Performance of PRRSV-Negative growing-finishing pigs

Abstract A total of 479 weaned pigs [PIC Camborough × PIC 337; initial body weight (BW) = 26.8 kg; Porcine reproductive and respiratory syndrome virus, PRRSV-negative] were used to evaluate the effects of EnduraPig (PMI Additives), a patent-pending feed additive that has been designed to support health, performance, and immune function of pigs, on growth performance of growing-finishing pigs. Pigs were blocked by initial BW and gender and assigned to 48 pens, which were allotted to one of 4 dietary treatments (12 pens/treatment, 9-10 pigs/pen), including T1) Control, T2) EnduraPig 0.1% (EP low), T3) EnduraPig 0.2% (EP medium), and T4) EnduraPig 0.3% (EP high). The EnduraPig inclusion levels were reduced by one-half when pigs reached approximately 70 kg BW (d 42). A five-phase feeding program was used with all diets formulated on a corn-DDGS-soybean meal basis to meet the nutrient requirements of growing-finishing pigs. Analysis of variance for growth measures was performed using the MIXED Procedure of SAS (SAS 9.4), and polynomial contrasts were used to evaluate linear, quadratic, and cubic effects of the EP levels. Significant differences were declared at P ≤ 0.05 and trends at P ≤ 0.10. During d 0-72, feeding EnduraPig tended to improve average daily gain (ADG) (0.96, 0.97, 1.00, and 0.97 kg, respectively; cubic, P = 0.06) with the greatest ADG observed in EP medium. During d 72 to market, feeding EnduraPig increased ADG (1.13, 1.14, 1.18, and 1.17 kg, respectively; linear, P = 0.02), average daily feed intake (ADFI; 3.48, 3.42, 3.55, and 3.49, respectively; cubic, P = 0.02) and feed:gain (3.08, 3.00, 3.01, and 2.98, respectively; linear, P = 0.10). Overall (d 0-market), feeding EnduraPig enhanced ADG (1.02, 1.02, 1.05, and 1.03 kg, respectively; linear, quadratic, and cubic, P = 0.04, 0.09, 0.01), with the greatest ADG observed in EP medium resulting in a 4.0 kg greater market BW compared with the control (128.9, 129.2, 132.9, and 130.5, respectively; linear and cubic, P < 0.05). In addition, feeding EnduraPig numerically improved feed:gain (2.51, 2.48, 2.48, and 2.48, respectively; linear, P = 0.14). With respect to BW variation, feeding EnduraPig reduced the standard deviation in market BW (10.65, 8.06, 8.86, and 9.54 kg, respectively; quadratic, P < 0.05), with the greatest reduction from EP low and EP medium (by 24 and 17%, respectively) compared with the control. In summary, data from this study indicate that feeding EnduraPig at 0.2% from 27 kg to 70 kg BW and 0.1% from 70 to market improves growth performance and reduces BW variation of PRRSV-negative growing-finishing pigs.

The Association Between Ventricular Fibrillation and Serum Catecholamine Levels.

Background and objective Epinephrine (Ep) is the first choice as a vasoconstrictor in cardiopulmonary resuscitation (CPR) for patients with cardiopulmonary arrest (CPA); however, the Ep concentration in the serum of CPA patients is still unclear. The aim of this study was to evaluate the association between serum Ep levels and achieving the return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation (VF). Methods This was a prospective, observational clinical study involving OHCA patients with VFtransferred to our hospital from July 2014 to July 2017. The measurement of serum catecholamines [Ep, norepinephrine (Nep), and dopamine (DOA)] and vasopressin [antidiuretic hormone (ADH)] levels was performed with blood samples obtained immediately upon patients' arrival at our hospital. Patients were classified into two groups: the ROSC(+) group and ROSC(-) group; the serum concentrations of catecholamines and ADH were compared between these two groups. Results The serum Ep and Nep levels were lower in the ROSC(+) group than those in the ROSC(-) group and the difference was statistically significant. On the other hand, no significant differences were found in serum DOA and ADH levels between the two groups. Conclusions The results of this study suggest that an increment in serum Ep levels does not promote achieving ROSC in OHCA patients with VF.

Leisure-Time Physical Activity Has a More Favourable Impact on Carotid Artery Stiffness Than Vigorous Physical Activity in Hypertensive Human Beings.

Aim. To assess the effect of leisure time versus vigorous long-term dynamic physical activity (PA) on carotid stiffness in normotensive versus hypertensive subjects. Methods. The study was conducted on 120 leisure-time exercisers and 120 competitive athletes. One hundred and twenty sedentary subjects served as controls. In addition, participants were classified according to whether their systolic blood pressure was ≥130 mmHg (hypertensives, n = 120) or normal (normotensives, n = 240) according to the ACC/AHA 2017 definition. Carotid artery stiffness was assessed with an echo-tracking ultrasound system, using the pressure-strain elastic modulus (EP) and one-point pulse wave velocity (PWVβ) as parameters of stiffness. Results. The effect of the two levels of PA differed in the normotensives and the hypertensives. Among the normotensives, there was an ongoing, graded reduction in EP and PWVβ from the sedentary subjects to the athletes. By contrast, among the hypertensives, the lowest levels of EP and PWVβ were found among the leisure-time PA participants. EP and PWVβ did not differ between the hypertensive sedentary subjects and the athletes. A significant interaction was found between PA and BP status on EP (p = 0.03) and a borderline interaction on PWVβ (p = 0.06). In multiple regression analyses, PA was a negative predictor of EP (p = 0.001) and PWVβ (p = 0.0001). The strength of the association was weakened after the inclusion of heart rate in the models (p = 0.04 and 0.007, respectively). Conclusions. These data indicate that in people with hypertension, leisure-time PA has beneficial effects on carotid artery stiffness, whereas high-intensity chronic PA provides no benefit to vascular functions.

Influence of the prehospital administered dosage of epinephrine on the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest

AimThis study evaluated whether the prehospital administered dosage of epinephrine (Ep) influences the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest (OHCA). MethodsThis was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were analyzed. The plasma levels of catecholamines were measured using blood samples obtained immediately upon arrival at the hospital and before the administration of Ep. Patients were divided into three groups based on the prehospital administered dosage of Ep: no prehospital administration (group Z); 1 mg of Ep (group O); and 2 mg of Ep (group T). The levels of catecholamines, as well as the conditions of resuscitation prior to and after arrival at the hospital were compared between the three groups. ResultsWe analyzed 145 patients with OHCA (96, 38, and 11 patients in groups Z, O, and T, respectively). Group T exhibited the highest plasma levels of Ep with a statistically significant difference, however, there were no significant differences in the plasma levels of norepinephrine (Nep), dopamine (DOA) and vasopressin (ADH) among the three groups. ConclusionThe prehospital administered dosage of Ep influences the plasma levels of Ep; however, it does not contribute to the plasma levels of Nep, DOA and ADH in patients with OHCA.

Relationship between the Plasma Levels of Catecholamines and Return of Spontaneous Circulation in Patients with Out-of-Hospital Cardiac Arrest.

Purpose The dynamic state of epinephrine (Ep) in the plasma of patients with out-of-hospital cardiac arrest (OHCA) remains unclear. The purpose of this study was to evaluate the relationship between the plasma levels of catecholamines (such as epinephrine (Ep), norepinephrine (Nep), and dopamine) and vasopressin (antidiuretic hormone (ADH)) and the acquisition of return of spontaneous circulation (ROSC) in OHCA patients. Methods This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were enrolled. The levels of catecholamines and ADH in the plasma were measured using blood samples immediately obtained on arrival at our hospital and before the administration of Ep. Patients in whom Ep was already administered prior to obtaining blood samples were excluded. Patients were divided into two groups: with and without ROSC, that is, ROSC (+) and ROSC (−) groups, respectively. The plasma levels of these agents and the conditions of resuscitation were compared between the two groups. Results A total of 96 patients with OHCA were analyzed. The ROSC (+) and ROSC (−) groups included 34 and 62 patients, respectively. There were no significant differences observed between the two groups in age, cause of cardiopulmonary arrest, and prehospital resuscitation time. The plasma levels of Ep and Nep were significantly lower in the ROSC (+) group than in the ROSC (−) group. However, there were no significant differences in the plasma levels of dopamine and ADH between the two groups. Conclusion Increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with OHCA.

Abstract 168: Relation Between the Prehospital Administrated Doses of Epinephrine and the Acquisition of Return of Spontaneous Circulation in Patients With Cardiopulmonary Arrest

Introduction: The efficacy of epinephrine (Ep) administration to cardiopulmonary arrest (CPA) patients is still controversial, and correlation between plasma Ep levels of and prognosis in CPA patients is unclear. Hypothesis: We hypothesized that the more EP is administered, the higher the rate of ROSC becomes in CPA patients. The purpose of this study is to evaluate whether a dose of Ep influenced the prognosis in CPA patients. Methods: This was a prospective, observational clinical study, approved by the ethics committee of Gunma University Hospital (IRB #14-13). CPA patients transferred to our hospital were enrolled prospectively between July 2014 and July 2017. The levels of Ep in the plasma were measured using blood samples immediately obtained at the time of arrival to our hospital. Patients were divided into the four groups based on the prehospital administered dose of EP; patients without prehospital Ep administration (group Z), prehospital administration of 1mg Ep (group O), 2mg Ep (group T) and 4mg Ep (group F). The plasma Ep levels and the conditions of resuscitation were compared among those groups. The IBM SPSS Statistics 25 software was used for statistical analysis. Data are shown as median (Q1, Q3). The Kruskal-Wallis or chi-square tests were used to conduct the comparisons among four groups. P<0.05 denoted statistical significance. Results: We analyzed 150 patients. There were 96 patients in group Z, 38 in group O, 11 in group T and 5 in group F. There was no significant difference in prehospital resuscitation time among 4 groups, and the level of Ep in the plasma obtained immediately after arrival at hospital was the highest in the group F with a significant difference {286.0 (247.2, 424.9) ng/ml in group F, 244.0 (22.1, 620.3) ng/ml in group T, 1.6 (0.5, 4.5) ng/ml in group O and 2.0 (0.4, 4.5) ng/ml in group Z, respectively, p<0.001}. However, the ratio of ROSC acquisition was the lowest in the group F with a significant difference (0 in group F, 18.2% in group T, 15.8% in group O and 35.4% in group Z). Conclusions: Our results suggest that the prehospital administered dose of Ep is not relates with the acquisition of ROSC in patients with CPA.

Levels of Catecholamines in the Plasma of Patients with Cardiopulmonary Arrest.

So far, there remains a controversy regarding the efficacy of epinephrine (Ep) in patients with cardiopulmonary arrest (CPA). In this study, we evaluated the importance of the plasma levels of catecholamines prior to the administration of Ep in patients with CPA. Patients with out-of-hospital cardiac arrest (OHCA) who were transferred to Gunma University Hospital were enrolled prospectively between July 2014 and July 2017. The levels of catecholamines [Ep, norepinephrine (NEp), and dopamine] and vasopressin (antidiuretic hormone) in the plasma were measured using blood samples of cardiogenic patients with OHCA not treated with Ep. Patients were divided into two groups: the return of spontaneous circulation [ROSC (+) ] group and the no return of spontaneous circulation [ROSC (-) ] group. The plasma levels of these agents and the conditions of resuscitation were compared between these two groups. 48 patients with cardiogenic CPA had not been treated with Ep prior to obtaining the blood samples. The ROSC (+) and ROSC (-) groups included 14 and 34 patients, respectively. The frequency of prehospital defibrillation was significantly higher in the ROSC (+) group. However, the prehospital resuscitation time was significantly shorter in the ROSC (+) group. Moreover, the levels of Ep and NEp in the plasma were significantly lower in the ROSC (+) group. The increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with cardiogenic CPA.

Abstract 124: Levels of Catecholamines in the Plasma of Patients With Cardiopulmonary Arrest

Purpose: The efficacy of epinephrine (Ep) administration to patients with cardiopulmonary arrest (CPA) remains controversial, and correlation between plasma levels of catecholamines and prognosis in CPA patients is unclear. The purpose of this study is to evaluate the importance of the plasma levels of catecholamines at the time of admission to the hospital prior to the administration of Ep in CPA patients. Methods: This was a prospective, observational clinical study, approved by the ethics committee of Gunma University Hospital. Patients with CPA transferred to our hospital were enrolled prospectively between July 2014 and July 2017. The levels of catecholamines (Ep, norepinephrine [NEp], and dopamine [DOA]) and vasopressin (antidiuretic hormone [ADH]) in the plasma were measured using blood samples obtained at the time of admission to our hospital (prior to the administration of Ep). Patients were divided into two groups: the return of spontaneous circulation (ROSC)(+) group and the ROSC(-) group. The levels of these agents in the plasma and the conditions of resuscitation were compared between these two groups. Results: Blood samples were obtained from 170 patients. In 48 patients, the cause of CPA was cardiogenic and Ep was not administered prior to admission to the hospital. The ROSC(+) and ROSC(-) groups included 14 and 34 patients, respectively. The frequency of prehospital defibrillation was significantly higher in the ROSC(+) group, whereas prehospital resuscitation time was significantly shorter in the ROSC(+) group. Moreover, the levels of Ep and NEp in the plasma were significantly lower in the ROSC(+) group. Conclusions: Increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with cardiogenic CPA.

Trends in lung cancer emergency presentation in England, 2006\u20132013: is there a pattern by general practice?

BackgroundEmergency presentations (EP) represent over a third of all lung cancer admissions in England. Such presentations usually reflect late stage disease and are associated with poor survival. General practitioners (GPs) act as gate-keepers to secondary care and so we sought to understand the association between GP practice characteristics and lung cancer EP.MethodsData on general practice characteristics were extracted for all practices in England from the Quality Outcomes Framework, the Health and Social Care Information Centre, the GP Patient Survey, the Cancer Commissioning Toolkit and the area deprivation score for each practice. After linking these data to lung cancer patient registrations in 2006–2013, we explored trends in three types of EP, patient-led, GP-led and ‘other’, by general practice characteristics and by socio-demographic characteristics of patients.ResultsOverall proportions of lung cancer EP decreased from 37.9% in 2006 to 34.3% in 2013. Proportions of GP-led EP nearly halved during this period, from 28.3 to 16.3%, whilst patient-led emergency presentations rose from 62.1 to 66.7%. When focusing on practice-specific levels of EP, 14% of general practices had higher than expected proportions of EP at least once in 2006–13, but there was no evidence of clustering of patients within practice, meaning that none of the practice characteristics examined explained differing proportions of EP by practice.ConclusionWe found that the high proportion of lung cancer EP is not the result of a few practices with very abnormal patterns of EP, but of a large number of practices susceptible to reaching high proportions of EP. This suggests a system-wide issue, rather than problems with specific practices. High proportions of lung cancer EP are mainly the result of patient-initiated attendances in A&E. Our results demonstrate that interventions to encourage patients not to bypass primary care must be system wide rather than targeted at specific practices.

Environmental impacts of Italian beef production: A comparison between different systems

Livestock production, particularly beef supply chain, is charged as the major contributor to green-house gas (GHG) emissions, as well as, in land degradation and deforestation. Environmental impacts per kg of edible beef, however, vary largely due to differences in beef production systems. Thus, this study aimed to compare the cradle-to-farm gate sustainability of four different Italian beef production systems, in terms of land occupation (LO, m2/year), global warming (GWP, kg CO2 -eq), water depletion (WD, m3), acidification (AP, g SO2 -eq) and eutrophication (EP, g NO3 -eq) potentials by using the LCA methodology (SimaPro 8.01 PhD, PRé Consultants). The primary data were obtained from 25 farms: 7 farms conducting cow–calf operations, with specialized beef cattle maintained on pasture and finished in confinement, (Specialized extensive, SE); 6 farms conducting high grain fattening of specialized beef breed imported calves (Fattening systems, FS); 5 farms conducting cow-calf operations, with specialized beef animals constantly kept in confinement (Cow-calf intensive; CCI); 7 farms conducting cow–calf operations, with Podolian cattle (a native breed of Southern Italy) maintained on pasture and finished in confinement, (Podolian system; PoS). The functional unit was 1 kg of live weight of marketed beef cattle. Intensive systems (i.e. CCI and FS) showed lower GWP values than systems partially based on pasture such as PoS, and even SE (17.62 ± 1.78 and 21.94 ± 1.95 kg CO2 –eq vs 26.30 ± 1.65 and 25.41 ± 1.65 kg CO2 –eq, P < 0.01, for FS, CCI, SE, and PoS, respectively). No significant effect of production system on WD was observed. Acidification potential was significantly (P < 0.001) affected by production system with the highest values observed in CCI (0.30 ± 0.02 kg SO2 –eq) compared with the other three beef production systems. As for eutrophication potential, FS and PoS tended to show lower values compared with CCI and SE systems (961.71 ± 65.30 and 779.17 ± 70.53 g NO3 -eq vs 1009.20 ± 77.27 and 1009.71 ± 65.30 g NO3 –eq, respectively; P < 0.10). Significant differences (P < 0.001) were observed for LO between the four systems (177.71 ± 20.87 and 194.43 ± 20.87 m2/year vs 40.67 ± 22.54 and 32.60 ± 23.69 m2/year, for PoS and SE vs FS and CCI, respectively). However, as diets in intensive meat systems are mainly based on cereals products that humans could consume directly, the degree of competition with human nutrition should be another feature to be considered. About this aspect, although human edible protein conversion efficiency (HEPCE) was not significantly influenced by production system, PoS showed a higher HEPCE index (0.44 ± 0.08), particularly if compared with CCI system (0.17 ± 0.09), but also in comparison with groups FS and SE (0.34 ± 0.08 and 0.39 ± 0.08, respectively). In addition, grass-based systems may provide other non-commodity outputs and non-marketable public goods services named “ecosystem services” (e.g. provision of clean drinking water, preservation and enhancement of biodiversity, conservation of cultural landscapes, contribution to the socio-economic viability of many rural areas particularly in marginal areas, enhancement of meat quality and animal welfare as perceived by consumers). The present results showed a lower impact of the intensive beef production systems in terms of GWP and LO, whereas some of them were more impactful at AP and EP levels. However, in order to achieve a more accurate estimation of the impact of the beef production chain, particularly for traditional and extensive farming systems conducted in marginal areas, such as the Podolian system, further LCA studies are needed, taking into account the allocation of their ecosystem services.

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress

Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function.

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings.

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 microliters of sample, the essay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases in circulating Ep levels in physiological and clinical conditions known to be associated with stimulation of suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RIA inthe hematology clinic, which will most certainly be expanded with its more extensive use.

Prostaglandin E2 resistance in granulocytes from patients with aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is an inflammatory condition of the respiratory tract and is characterized by overproduction of leukotrienes (LT) and large numbers of circulating granulocyte-platelet complexes. LT production can be suppressed by prostaglandin E(2) (PGE(2)) and the cyclic AMP-dependent protein kinase A (PKA). To determine if PGE(2)-dependent control of LT production by granulocytes is dysregulated in AERD. Granulocytes from well-characterized patients with and without AERD were activated ex vivo and subjected to a range of functional and biochemical analyses. Granulocytes from subjects with AERD generated more LTB4 and cysteinyl LTs than did granulocytes from controls with aspirin-tolerant asthma and controls without asthma. When compared with controls, granulocytes from subjects with AERD had comparable levels of EP(2) protein expression and PGE(2)-mediated cAMP accumulation, yet were resistant to PGE(2)-mediated suppression of LT generation. Percentages of platelet-adherent neutrophils correlated positively with LTB4 generation and inversely with responsiveness to PGE(2)-mediated suppression of LTB(4). The PKA inhibitor H89 potentiated LTB4 generation by control granulocytes but was inactive in granulocytes from individuals with AERD and had no effect on platelet P-selectin induction. Both tonic PKA activity and levels of PKA catalytic gamma subunit protein were significantly lower in granulocytes from individuals with AERD relative to those from controls. Impaired granulocyte PKA function in AERD may lead to dysregulated control of 5-lipoxygenase activity by PGE(2), whereas adherent platelets lead to increased production of LTs, which contributes to the features of persistent respiratory tract inflammation and LT overproduction.

Yolk Formation in a Stony Coral Euphyllia ancora (Cnidaria, Anthozoa): Insight Into the Evolution of Vitellogenesis in Nonbilaterian Animals

Vitellogenin (Vg) is a major yolk protein precursor in numerous oviparous animals. Numerous studies in bilateral oviparous animals have shown that Vg sequences are conserved across taxa and that Vgs are synthesized by somatic-cell lineages, transported to and accumulated in oocytes, and eventually used for supporting embryogenesis. In nonbilateral animals (Polifera, Cnidaria, and Ctenophora), which are regarded as evolutionarily primitive, although Vg cDNA has been identified in 2 coral species from Cnidaria, relatively little is known about the characteristics of yolk formation in their bodies. To address this issue, we identified and characterized 2 cDNA encoding yolk proteins, Vg and egg protein (Ep), in the stony coral Euphyllia ancora. RT-PCR analysis revealed that expression levels of both Vg and Ep increased in the female colonies as coral approached the spawning season. In addition, high levels of both Vg and Ep transcripts were detected in the putative ovarian tissue, as determined by tissue distribution analysis. Further analyses using mRNA in situ hybridization and immunohistochemistry determined that, within the putative ovarian tissue, these yolk proteins are synthesized in the mesenterial somatic cells but not in oocytes themselves. Furthermore, Vg proteins that accumulated in eggs were most likely consumed during the coral embryonic development, as assessed by immunoblotting. The characteristics of Vg that we identified in corals were somewhat similar to those of Vg in bilaterian oviparous animals, raising the hypothesis that such characteristics were likely present in the oogenesis of some common ancestor prior to divergence of the cnidarian and bilaterian lineages.

Mirthful laughter, as adjunct therapy in diabetic care, attenuates catecholamines, inflammatory cytokines, C‐RP, and myocardial infarction occurrence

Objectives: Catecholamines are implicated in causing arrhythmias, hypertension, and MI. Inflammatory cytokines TNF‐α, IFN‐γ and IL‐6 contribute to the acceleration of atherosclerosis. Attenuation of catecholamines and inflammatory cytokines may provide cardiovascular protection. We hypothesized that mirthful laughter, by diminishing catecholamines production, can attenuate inflammatory cytokines, and provide cardiovascular protection.Methods: We divided 20 high risk diabetic patients with hypertension and hyperlipidemia into 2 matched groups and followed them for one year in our Metabolic Syndrome Clinic. The experimental group was asked to view self‐selected humor for 30 minutes daily as an adjunct to standard diabetes (glipizide, TZD, metformin), hypertension (ACE inhibitor or ARB) and hyperlipidemia (statin) therapies. Plasma fractionated catecholamines levels, lipid panel, TNF‐α, IFN‐γ, IL‐6, and CRP were monitored and assayed every 2 months.Results: Patients in the laughter group had lower EP and NEP levels by 2 months, increased HDL cholesterol, decreased TNF‐α, IFN‐γ, IL‐6 and CRP levels by 4 months, and a lower incidence of MI (1/10) than the control group (3/10).Conclusions: Addition of mirthful laughter may be an effective cardiovascular preventive adjunct in diabetes mellitus and metabolic syndrome care. These effects may contribute to lower MI occurrence.

Suppressive effect of clozapine but not haloperidol on the increases of neuropeptide-degrading enzymes and glial cells in MK-801-treated rat brain regions

MK-801, a noncompetitive N-methyl- d-aspartate (NMDA) receptor antagonist, produces neurotoxicity in adult rodent brain, and causes schizophrenia-like psychosis and cognitive dysfunction. Since neuropeptides and neuropeptide-degrading enzymes play important roles in cognitive function, we examined whether or not MK-801-induced schizophrenia-like psychosis is co-related with the changes of these enzymes in rat brain regions. In the present study, we investigated the effect of systemic treatment with MK-801 (0.5 mg/kg) on neuropeptide-degrading enzymes, prolyl oligopeptidase (POP) and thimet oligopeptidase (EP 24.15), and glial marker proteins GFAP and CD11b in rat brain regions. The levels of POP and EP 24.15 activities increased significantly three days after treatment with MK-801 in the posterior cingulate/retrosplenial cortices (PC/RSC). Since atypical neuroleptic clozapine but not typical neuroleptic haloperidol prevents the MK-801-induced schizophrenia-like symptoms, we further examined the pretreated effects of the neuroleptics. Clozapine, but not haloperidol, significantly attenuated MK-801-induced changes in the levels of the neuropeptide-degrading enzymes. Immunohistochemical studies on GFAP and CD11b showed the increase in the PC/RSC of MK-801-treated rat brain and the pretreatment with clozapine suppressed these changes. Double immunostain experiments of EP 24.15 and GFAP antibodies demonstrated some co-localization of the neuropeptidase with astrocytes. The present findings suggest that change of neuropeptidases in the brain is in part correlated with changes of glial cells, and may play an important role in the control of schizophrenia-like psychotic disorders.

Binding of a Single Rb+ Increases Na+/K+-ATPase, Activating Dephosphorylation without Stoichiometric Occlusion

We used partially purified Na+/K+-ATPase from pig kidney to study dephosphorylation, occlusion, and ATPase activity in the same enzyme preparation and in media of identical composition containing 10 microM ATP and different concentrations of Rb+, used as a K+ congener. The experiments were performed using a rapid-mixing apparatus with a time resolution of 3.5 ms. The main findings were as follows. (i) At sufficiently low Rb+ concentration the initial rate of dephosphorylation was higher than that of occlusion, (ii) as [Rb+] tended to zero the slope of the time course of occlusion but not that of the time course of dephosphorylation approached zero and, (iii) as Rb+ concentration increased, ATPase activity first increased and, after passing through a maximum, tended to a value that was lower than that observed in media without Rb+. None of these results is compatible with the currently held idea that binding of a single Rb+ to the E2P conformer of the ATPase does not modify the rate of dephosphorylation and strongly suggest that a single Rb+ does promote dephosphorylation through a mechanism that is not stoichiometrically coupled to Rb+ occlusion. If this mechanism is included in the currently accepted scheme for ATP hydrolysis by the Na+/K+-ATPase, a reasonable prediction of the experimental results is obtained.

Dynamic contrast‐enhanced MRI for assessing the disease activity of multiple myeloma: A comparative study with histology and clinical markers

To examine whether parameters of dynamic, contrast-enhanced MRI (DCE MRI) reflect the degree of infiltration and vessel density in corresponding bone marrow biopsy specimens. The pelvis of 24 patients with multiple myeloma (MM) was examined using contrast-enhanced DCE MRI. Biopsy was obtained from the spina iliaca posterior superior. Using a two-compartment model (assuming one intravascular and one interstitial compartment), the parameters amplitude (A, the maximum, relative signal increase over baseline) and the exchange rate constant (k(ep), describing the redistribution of contrast agent from the interstitial into the intravascular compartment) in the biopsied region were calculated and compared with the histological and clinical data. DCE MRI parameters were significantly higher in lesions with marked infiltration than with mild or no infiltration (P < 0.05). The amplitude normalized to that in the iliac artery (A(n)), but not k(ep), was higher in lesions with high vessel-density at histology (P = 0.01). Higher k(ep) levels were found in presence of increased serum immunoglobulins. Increased contrast uptake in the bone marrow of MM patients indicates at least moderate tumor involvement. Furthermore, the contrast enhancement correlates with vessel-density and serum markers of disease activity.