bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity-dependent feedback modulation of spike patterning of supraoptic nucleus neurons by endogenous adenosine
Authors: Bull P. M. , Brown C. H. , Russell J. A. , Ludwig M.
Published: February 2006

Neuropeptide secretion from the dendrites of hypothalamic magnocellular supraoptic nucleus (SON) neurons contributes to the regulation of neuronal activity patterning, which ultimately determines their peptide output from axon terminals in the posterior pituitary gland. SON dendrites also secrete a number of other neuromodulators, including ATP. ATP degrades to adenosine in the extracellular space to complement transported adenosine acting on pre- and postsynaptic SON A1 receptors to reduce neuronal excitability, measured in vitro. To assess adenosine control of electrical activity in vivo, we made extracellular single-unit recordings of the electrical activity of SON neurons in anesthetized male rats. Microdialysis application (retrodialysis) of the A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased phasic vasopressin cell intraburst firing rates progressively over the first 5 s by 4.5 ± 1.6 Hz ( P < 0.05), and increased burst duration by 293 ± 64% ( P < 0.05). Hazard function plots were generated from interval interspike histograms and revealed that these effects were associated with increased postspike excitability. In contrast, CPT had no effect on the firing rates and hazard function plot profiles of continuously active vasopressin and oxytocin cells. However, CPT significantly increased clustering of spikes, as quantified by the index of dispersion, in oxytocin cells and continuously active vasopressin cells (by 267 ± 113% and 462 ± 67%, respectively, P < 0.05). Indeed, in 4 of 5 continuously active vasopressin cells, CPT induced a pseudophasic activity pattern. Together, these results indicate that endogenous adenosine is involved in the local control of SON cell activity in vivo.
Fluorescein-methotrexate transport in dogfish shark (Squalus acanthias) choroid plexus
Authors: Baehr Carsten H. , Fricker Gert , Miller David S.
Published: February 2006

The vertebrate choroid plexus removes potentially toxic metabolites and xenobiotics from cerebrospinal fluid (CSF) to blood for subsequent excretion in urine and bile. We used confocal microscopy and quantitative image analysis to characterize the mechanisms driving transport of the large organic anion, fluorescein-methotrexate (FL-MTX), from bath (CSF-side) to blood vessels in intact lateral choroid plexus from dogfish shark, Squalus acanthias, an evolutionarily ancient vertebrate. With 2 μM FL-MTX in the bath, steady-state fluorescence in the subepithelium/vascular space exceeded bath levels by 5- to 10-fold, and fluorescence in the epithelial cells was slightly below bath levels. FL-MTX accumulation in both tissue compartments was reduced by NaCN, Na removal, and ouabain, but not by a 10-fold increase in medium K. Certain organic anions, e.g., probenecid, MTX, and taurocholate, reduced FL-MTX accumulation in both tissue compartments; p-aminohippurate and estrone sulfate reduced subepithelial/vascular accumulation, but not cellular accumulation. At low concentrations, digoxin, leukotriene C4, and MK-571 reduced fluorescence in the subepithelium/vascular space while increasing cellular fluorescence, indicating preferential inhibition of efflux over uptake. In the presence of 10 μM digoxin (reduced efflux, enhanced cellular accumulation), cellular FL-MTX accumulation was specific, concentrative, and Na dependent. Thus transepithelial FL-MTX transport involved the following two carrier-mediated steps: electroneutral, Na-dependent uptake at the apical membrane and electroneutral efflux at the basolateral membrane. Finally, FL-MTX accumulation in both tissue compartments was reduced by phorbol ester and increased by forskolin, indicating antagonistic modulation by protein kinase C and protein kinase A.
Aging alters regulation of visceral sympathetic nerve responses to acute hypothermia
Authors: Helwig Bryan G. , Parimi Sujatha , Ganta Chanran K. , Cober Richard , Fels Richard J. , Kenney Michael J.
Published: February 2006

Hypothermia produced by acute cooling prominently alters sympathetic nerve outflow. Skin sympathoexcitatory responses to skin cooling are attenuated in aged compared with young subjects, suggesting that advancing age influences sympathetic nerve responsiveness to hypothermia. However, regulation of skin sympathetic nerve discharge (SND) is only one component of the complex sympathetic nerve response profile to hypothermia. Whether aging alters the responsiveness of sympathetic nerves innervating other targets during acute cooling is not known. In the present study, using multifiber recordings of splenic, renal, and adrenal sympathetic nerve activity, we tested the hypothesis that hypothermia-induced changes in visceral SND would be attenuated in middle-aged and aged compared with young Fischer 344 (F344) rats. Colonic temperature (Tc) was progressively reduced from 38°C to 31°C in young (3 to 6 mo), middle-aged (12 mo), and aged (24 mo) baroreceptor-innervated and sinoaortic-denervated (SAD), urethane-chloralose anesthetized, F344 rats. The following observations were made. 1) Progressive hypothermia significantly ( P < 0.05) reduced splenic, renal, and adrenal SND in young baroreceptor-innervated F344 rats. 2) Reductions in splenic, renal, and adrenal SND to progressive hypothermia were less consistently observed and, when observed, were generally attenuated in baroreceptor-innervated middle-aged and aged compared with young F344 rats. 3) Differences in splenic, renal, and adrenal SND responses to reduced Tc were observed in SAD young, middle-aged, and aged F344 rats, suggesting that age-associated attenuations in SND responses to acute cooling are not the result of age-dependent modifications in arterial baroreflex regulation of SND. These findings demonstrate that advancing chronological age alters the regulation of visceral SND responses to progressive hypothermia, modifications that may contribute to the inability of aged individuals to adequately respond to acute bouts of hypothermia.
Effects of chest wall strapping on mechanical response to methacholine in humans
Authors: Torchio Roberto , Gulotta Carlo , Ciacco Claudio , Perboni Alberto , Guglielmo Marco , Crosa Flavio , Zerbini Mario , Brusasco Vito , Hyatt Robert E. , Pellegrino Riccardo
Published: February 2006

We examined the effects of chest wall strapping (CWS) on the response to inhaled methacholine (MCh) and the effects of deep inspiration (DI). Eight subjects were studied on 1 day with MCh inhaled without CWS (CTRL), 1 day with MCh inhaled during CWS (CWSon/on), and 1 day with MCh inhaled during temporary removal of CWS (CWSoff/on). On the CWSon/on day, MCh caused greater increases in pulmonary resistance, upstream resistance, dynamic elastance, residual volume, and greater decreases in maximal expiratory flow than on the CTRL day. On the CWSoff/on day, the changes in these parameters with MCh were not different from the CTRL day. Six of the subjects were again studied using the same protocol on CTRL and CWSon/on days, except that, on a third day, MCh was given after applying the CWS, but the measurements before and after the inhalation were made without CWS (CWSon/off). The latter sequence was associated with more severe airflow obstruction than during CTRL, but less than with CWSon/on. The bronchodilator effects of a DI were blunted when CWS was applied during measurements (CWSon/on and CWSoff/on) but not after it was removed (CWSon/off). We conclude that CWS is capable of increasing airway responsiveness only when it is applied during the inhalation of the constrictor agent. We speculate that breathing at low lung volumes induced by CWS enhances airway narrowing because the airway smooth muscle is adapted at a length at which the contractile apparatus is able to generate a force greater than normal.
Hemostatic response to postprandial lipemia before and after exercise training
Authors: Paton Chad M. , Brandauer Josef , Weiss Edward P. , Brown Michael D. , Ivey F. M. , Roth Stephen M. , Hagberg James M.
Published: February 2006

Chronic hypertriglyceridemia is thought to be atherogenic and is associated with an elevated thrombotic potential, both of which may be improved with aerobic exercise training. Eight subjects were tested for aerobic capacity, body composition, and postprandial lipemia (PPL), followed by 6 mo of exercise training and final testing. Blood samples were obtained for measurement of free fatty acid (FFA), triglycerides (TG), insulin (Ins), and glucose (Glu). Hemostatic variables including factor VII activity (FVIIa), tissue factor pathway inhibitor-factor Xa complex (TFPI/Xa), and plasminogen activator inhibitor-1 (PAI-1) antigen/activity as well as leukocyte tumor necrosis factor-α (TNF-α) gene expression were determined among four subjects. We found that the exercise training was of sufficient intensity to increase aerobic capacity ( P < 0.0001) and improve body composition ( P = 0.04). There were no differences between tests among PPL responses of FFA, TG, Ins, or Glu; however, the mean TG response and fat oxidation rate improved. PAI-1 antigen/activity, FVIIa, TFPI/Xa, and TNF-α gene expression were all improved after exercise training after adjusting for confounders. We conclude that aerobic exercise training reduces the potential for coagulation, improves fibrinolytic potential, and reduces leukocyte TNF-α gene expression after the ingestion of a high-fat meal.
Gender differences in the decline in aerobic capacity and its physiological determinants during the later decades of life
Authors: Weiss Edward P. , Spina Robert J. , Holloszy John O. , Ehsani Ali A.
Published: February 2006

We investigated the hemodynamic determinants of the age-associated decline in maximal oxygen uptake (V̇o2 max) and the influence of gender on the decline in V̇o2 max and its determinants in old and very old men and women. Sedentary, 60- to 92-yr-old women ( n = 71) and men ( n = 29), with no evidence of cardiovascular disease, underwent maximal treadmill exercise tests during which V̇o2 max and maximal cardiac output (Q̇max) were determined. V̇o2 max and age were inversely related in both women (−23 ± 2 ml·min−1·yr−1; P < 0.0001) and men (−57 ± 5 ml·min−1·yr−1; P < 0.0001). The absolute slope of the V̇o2 max vs. age relationship was twofold steeper in men than in women ( P < 0.0001). Q̇max was also inversely related to age in a gender-specific manner (women = −87 ± 25 ml·min−1·yr−1, P = 0.0009; men = −215 ± 50 ml·min−1·yr−1, P = 0.0002; P = 0.01 women vs. men). Age-related changes in maximal exercise arteriovenous oxygen content difference (a-vDo2) were marginally different ( P = 0.08) between women (−0.12 ± 0.03 ml·dl−1·yr−1, P = 0.0003) and men (−0.22 ± 0.04 ml·dl−1·yr−1, P < 0.0001). Age-associated decreases in Q̇max and a-vDo2 contributed equally to the declines in V̇o2 max in both men and women. In the later stages of life, V̇o2 max, Q̇max, and a-vDo2 decrease with age more rapidly in older men than they do in older women. As a result, the gender differences dissipate in the later decades of life. Declines in Q̇max and a-vDo2 contribute equally to the age-related decrease in V̇o2 max in men and women.
Arginine-vasopressin mediates central and peripheral glucose regulation in response to carotid body receptor stimulation with Na-cyanide
Authors: Montero Sergio , Mendoza Herón , Valles Victoria , Lemus Mónica , Alvarez-Buylla Ramón , de Alvarez-Buylla Elena R.
Published: February 2006

Hypoxic stimulation of the carotid body receptors (CBR) results in a rapid hyperglycemia with an increase in brain glucose retention. Previous work indicates that neurohypophysectomy inhibits this hyperglycemic response. Here, we show that systemic arginine vasopressin (AVP) induced a transient, but significant, increase in blood glucose levels and increased brain glucose retention, a response similar to that observed after CBR stimulation. Comparable results were obtained after intracerebral infusion of AVP. Systemic AVP-induced changes were maintained in hypophysectomized rats but were not observed after adrenalectomy. Glycemic changes after CBR stimulation were inhibited by pharmacological blockage of AVP V1a receptors with a V1a-selective receptor antagonist ([β-Mercapto-β,β-cyclopentamethylenepropionyl1,O-me-Tyr2, Arg8]-vasopressin). Importantly, local application of micro-doses of this antagonist to the liver was sufficient to abolish the hyperglycemic response after CBR stimulation. These results suggest that AVP is a mediator of the hyperglycemic reflex and cerebral glucose retention following CBR stimulation. We propose that hepatic activation of AVP V1a receptors is essential for this hyperglycemic response.
Vascular wall energetics in arterioles during nitric oxide-dependent and -independent vasodilation
Authors: Shibata Masahiro , Qin Kairong , Ichioka Shigeru , Kamiya Akira
Published: February 2006

The objective of this study was to evaluate whether the nitric oxide (NO) released from vascular endothelial cells would decrease vessel wall oxygen consumption by decreasing the energy expenditure of mechanical work by vascular smooth muscle. The oxygen consumption rate of arteriolar walls in rat cremaster muscle was determined in vivo during NO-dependent and -independent vasodilation on the basis of the intra- and perivascular oxygen tension (Po2) measured by phosphorescence quenching laser microscopy. NO-dependent vasodilation was induced by increased NO production due to increased blood flow, whereas NO-independent vasodilation was induced by topical administration of papaverine. The energy efficiency of vessel walls was evaluated by the variable ratio of circumferential wall stress (amount of mechanical work) to vessel wall oxygen consumption rate (energy cost) in the arteriole between normal and vasodilated conditions. NO-dependent and -independent dilation increased arteriolar diameters by 13 and 17%, respectively, relative to the values under normal condition. Vessel wall oxygen consumption decreased significantly during both NO-dependent and -independent vasodilation compared with that under normal condition. However, vessel wall oxygen consumption during NO-independent vasodilation was significantly lower than that during NO-dependent vasodilation. On the other hand, there was no significant difference between the energy efficiency of vessel walls during NO-dependent and -independent vasodilation, suggesting the decrease in vessel wall oxygen consumption produced by NO to be related to reduced mechanical work of vascular smooth muscle.
Sudden Cardiac Death in the Young: A Strategy for Prevention by Targeted Evaluation
Authors: Sen-Chowdhry Srijita , McKenna William J.
Published: February 2006

The annual incidence of sudden cardiac death (SCD) in the general population is estimated as 1 in a 1,000. Since survival rates from out-of-hospital cardiac arrests are poor, primary prevention is key to reducing the burden of SCD in the community. Prominent causes of SCD include ischaemic heart disease, anomalous coronary arteries, and the primary myocardial diseases: hypertrophic cardiomyopathy, dilated cardiomyopathy, and ar rhythmogenic right ventricular cardiomyopathy (ARVC). In 4% of sudden deaths in the 16–64 age group, post-mortem examination fails to identify a cause, yielding a default diagnosis of sudden arrhythmic death syndrome (SADS). The inherited arrhythmia syndromes (long QT, short QT, and Brugada syndromes, and familial catecholaminergic polymorphic ventricular tachycardia) may be implicated in SADS, owing to their propensity for producing ventricular tachyarrhythmia in the structurally normal heart. Monogenic disorders therefore predominate as causes of SCD in the young. The advent of effective therapies for these diseases, particularly implantable cardioverter defibrillators, has prompted calls for universal screening to enable timely diagnosis of occult cardiac disease. Since prospective cardiac assessment of the general population is not feasible, the solution may be to target high-risk subgroups, namely, patients with cardiac symptoms, relatives of SCD victims, and competitive athletes. The recommended preliminary work-up includes a 12-lead ECG, signal-averaged ECG, transthoracic echocardiogram, exercise test, and ambulatory ECG monitoring. Cardiovascular magnetic resonance is a useful adjunct in patients with suspected ARVC or anomalous coronary arteries. Provocative challenge with a sodium challenge blocker may be of value in unmasking the Brugada syndrome. Identification of disease-causing mutations in affected individuals facilitates cascade screening of families.
Iron Availability and Consumption of Tea, Vervain and Mint during Weaning in Morocco
Authors: Zaida F. , Bureau F. , Guyot S. , Sedki A. , Lekouch N. , Arhan P. , Bouglé D.
Published: February 2006

Background/Aims: Iron deficiency impairs growth and psychomotor development of infants. In Morocco, infusions are introduced very early in infant diet, and could contribute to iron deficiency, due to their high polyphenol content. Methods: The availability of tea, mint and vervain infusions was assessed using an in vitro model of digestion and dialysis. Two gastric pHs were used: pH 4 as in the first week life, and pH 2.5 as in older infants. Six repetitions of each experiment were made. The total polyphenol content of infusions was measured. Results: At pH 4 and at pH 2.5, iron availability was decreased by tea and vervain, and increased by mint and ascorbic acid. At both pHs it was increased by addition of ascorbic acid to tea and vervain. In addition, at pH 2.5 it was increased by addition of ascorbic acid to mint. The highest value was observed in the presence of both ascorbic acid and mint (33.1 ± 4.1%). In any case, iron availability was higher at pH 2.5 than at pH 4 (with single compounds or combinations with ascorbic acid). The polyphenol contents (mg/l) of tea, vervain and mint infusions were 2,236.1, 771.1, and 16.5. Conclusions: Tea and vervain infusions inhibited iron availability. In contrast, mint improved it; vitamin C helped in preventing these inhibiting properties. It could be proposed to discourage tea and vervain drinking at early weaning and to replace them by mint infusion, or at least to promote the consumption of vitamin C-rich fruit juice to counteract these inhibiting effects.
Influence of Folate Serum Concentration on Plasma Homocysteine Levels in HIV-Positive Patients Exposed to Protease Inhibitors Undergoing HAART
Authors: Uccelli Maria Cristina , Torti Carlo , Lapadula Giuseppe , Labate Lorena , Cologni Giuliana , Tirelli Valeria , Moretti Francesca , Costarelli Silvia , Quiros-Roldan Eugenia , Carosi Giampiero
Published: February 2006

Background: Homocysteinemia (Hcy) increase and risk factors in HIV-positive patients are not clear yet. Methods: HIV-positive patients on stable highly active antiretroviral therapy (HAART) regimens for at least 6 months were enrolled in this cross-sectional study. Among other factors, vitamin B12, folate and length of exposure to protease inhibitors (PIs) were evaluated for their possible correlation with hyper-Hcy (>13 µmol/l in females; >15 µmol/l in males) by logistic regression analysis. Results: Ninety-eight HIV-positive patients were recruited. Twenty-eight (28.6%) had hyper-Hcy. Length of exposure to antiretroviral therapy and PIs did not result to be significantly associated with hyper-Hcy risk. Normal folate level was the only factor associated with the outcome, resulting protective from hyper-Hcy, either at univariate (OR = 0.22; CI 95% = 0.06–0.86; p = 0.029) and multivariable (OR = 0.24; CI 95% = 0.06–0.94; p = 0.04) logistic regression analysis. Folate predictive value of hyper-Hcy risk was driven by levels in the lowest quartiles of the study population (i.e. <10.9 nmol/l). Conclusions: No significant correlations were observed between hyper-Hcy and length of exposure to antiretroviral therapy or PIs. Folate could be a confounding factor in the association between hyper-Hcy and PI exposure found by others. The potential value of folate supplementation, in those who are deficient and in those with hyper-Hcy, merits study.
Safety and Efficacy of a New Parenteral Lipid Emulsion (SMOFlipid) in Surgical Patients: A Randomized, Double-Blind, Multicenter Study
Authors: Mertes Norbert , Grimm Helmut , Fürst Peter , Stehle Peter
Published: February 2006

Background/Aims: A new lipid emulsion based on soybean oil, medium chain triglycerides, olive oil and fish oil (SMOFlipid) was tested for safety, tolerance, metabolic and clinical efficacy in surgical patients. Methods: In a prospective, double-blind European multicenter study, postoperative patients (elective abdominal or thoracic surgery) were randomized to receive isonitrogenous, isoenergetic (30–35 kcal/kg) total parenteral nutrition over 5 postoperative days including either SMOFlipid® 20% or standard soybean oil emulsion (Lipovenoes® 20%) as lipid source (1.5 g kg–1 day–1). Metabolic efficacy measurements included serum levels of triglycerides (AUC), phospholipids, and total cholesterol. Safety/tolerance parameters were: hematology; clinical chemistry; coagulation profile; clinical course (arterial blood pressure, heart rate, body temperature), and documentation of adverse events. Clinical efficacy was monitored by length of hospital stay and mortality. Results: The 2 groups (per-protocol population: SMOFlipid n = 99, and Lipovenoes n = 100) were similar with respect to demographic characteristics and types of surgical intervention. Concentrations of serum triglycerides, phospholipids, and total cholesterol were comparable in both groups and within the expected ranges. Laboratory and clinical parameters were not different. A trend towards a reduced length of hospital stay was observed with SMOFlipid (15.7 ± 6.3 vs. 17.8 ± 13.2 days). Conclusions: SMOFlipid is clinically safe and well tolerated in postoperative patients. There are indications that SMOFlipid may be associated with a better liver tolerance and a shorter length of hospitalization.
Variations in Postprandial Ghrelin Status following Ingestion of High-Carbohydrate, High-Fat, and High-Protein Meals in Males
Authors: Tannous dit El Khoury Dalia , Obeid Omar , Azar Sami T. , Hwalla Nahla
Published: February 2006

Aim: The purpose of this study was to investigate the response of postprandial acylated ghrelin to changes in macronutrient composition of meals in healthy adult males. Methods: A randomized crossover study was performed. Ten healthy adult males were recruited. All subjects received, on separate occasions, a high-carbohydrate (HC), a high-fat (HF), and a high-protein (HP) meal. Blood samples were collected before and 15, 30, 60, 120, and 180 min following the ingestion of each meal. Plasma acylated ghrelin as well as serum insulin, glucose, and triglycerides were measured. Results: The levels of acylated ghrelin fell significantly following the three meals. The HC meal induced the most significant decrease in postprandial ghrelin secretion (–15.5 ± 2.53 pg/ml) as compared with HF (–8.4 ± 2.17 pg/ml) and HP (–10.0 ± 1.79 pg/ml) meals (p < 0.05). However, at 180 min, the HP meal maintained significantly lower mean ghrelin levels (29.7 ± 3.56 pg/ml) than both HC (58.4 ± 5.75 pg/ml) and HF (45.7 ± 5.89 pg/ml) meals and lower levels than baseline (43.4 ± 5.34 pg/ml) (p <0.01). The postprandial insulin levels increased to significantly higher levels following the HC meal (+80.6 ± 11.14 µU/ml) than following both HF (37.3 ± 4.82 µU/ml) and HP (51.4 ± 6.00 µU/ml) meals (p < 0.001). However, at 180 min, the mean insulin levels were found to be significantly higher following the HP meal (56.4 ± 10.80 µU/ml) as compared with both HC (30.9 ± 4.31 µU/ml) and HF (33.7 ± 4.42 µU/ml) meals (p < 0.05). Acylated ghrelin was also found to be negatively correlated with circulating insulin levels, across all meals. Conclusions: These results indicate that the nutrient composition of meals affects the extent of suppression of postprandial ghrelin levels and that partial substitution of dietary protein for carbohydrate or fat may promote longer-term postprandial ghrelin suppression and satiety. Our results also support the possible role of insulin in meal-induced ghrelin suppression.
Improvement of Lipid Profile by Amaranth (Amaranthus esculantus) Supplementation in Streptozotocin-Induced Diabetic Rats
Authors: Kim Hye Kyung , Kim Mi-Jeong , Shin Dong-Hoon
Published: February 2006

Background/Aims: Lipid disorders may exacerbate some complications of diabetes. Amaranth has been reported to exhibit a cholesterol-lowering effect in hyperlipidemic animals. The present study was designed to investigate the effect of amaranth on serum glucose and the lipid profile in diabetic rats. Methods: Male Sprague-Dawley rats were assigned to normal control, diabetic control, diabetic amaranth-grain (AG)-supplemented (500 g/kg diet) and diabetic amaranth-oil (AO)-supplemented (90 g/kg diet) groups and fed experimental diets for 3 weeks. Effects were monitored on glucose tolerance, serum and liver lipids, and fecal excretions of lipids and bile acids. Results: Fasting serum glucose levels and the glucose tolerance of diabetic rats were improved by AG and AO supplementation. Serum and liver lipids such as total cholesterol, triglyceride (TG) and very-low-density lipoprotein cholesterol concentrations were also lowered in diabetic animals by AG and AO consumption. Fecal excretions of cholesterol, TG and bile acid were markedly reduced in diabetic rats, and these parameters were dramatically increased by AG and AO supplementation. Conclusion: AG and AO supplementation improve the glucose and lipid metabolism in streptozotocin-induced diabetic rats.
The Effect of Nutritional Habits on Maternal-Neonatal Lipid and Lipoprotein Serum Levels in Three Different Ethnic Groups
Authors: Schulpis Kleopatra H. , Gavrili Stavroula , Vlachos George , Karikas George A. , Michalakakou Kelly , Demetriou Elisabeth , Papassotiriou Ioannis
Published: February 2006

Aim: To investigate the effect of nutritional habits on lipid profiles in mothers of three different ethnic groups and in their newborns. Subjects and Methods: Lipids and lipoproteins were determined in 7-day dietetic diaries of 9,134 mothers (Greeks n = 3,118, Albanians n = 3,050, Muslim Asians n = 2,966), in their sera and in the cord blood of their newborns with routine methods. Results: Monounsaturated fat intake (35 ± 12 g/day) was similar among the groups. Total fat, saturated fat and cholesterol intakes were significantly lower in Asians than those in Albanians and Greeks. Significantly lower lipid and lipoprotein concentrations (cholesterol 5.09 ± 0.85 mmol/l, triglyceride, TG, 2.38 ± 0.58 mmol/l, low-density lipoprotein cholesterol, LDL-C, 2.90 ± 0.78 mmol/l, very-low-density lipoprotein cholesterol, VLDL-C, 0.32 ± 0.11 mmol/l) were measured in the Muslim Asian mothers and in their newborns (cholesterol 1.06 ± 0.26 mmol/l, TG 0.52 ± 0.16 mmol/l, LDL-C 0.49 ± 0.10 mmol/l and VLDL-C 0.10 ± 0.02 mmol/l; p < 0.001). Higher levels of the mentioned biochemical parameters were found in Greek mothers versus their newborns (cholesterol 5.20 ± 0.98 mmol/l, TG 2.37 ± 0.62 mmol/l, LDL-C 3.40 ± 0.85 mmol/l and VLDL-C 0.48 ± 0.13 mmol/l vs. cholesterol 1.55 ± 0.31 mmol/l, TG 0.56 ± 0.20 mmol/l, LDL-C 0.65 ± 0.15 mmol/l and VLDL-C 0.12 ± 0.01 mmol/l; p < 0.001) and Albanian mothers versus their newborns (cholesterol 7.1 ± 0.78 mmol/l, TG 2.55 ± 0.60 mmol/l, LDL-C 4.1 ± 0.88 mmol/l and VLDL-C 0.52 ± 0.13 mmol/l vs. cholesterol 1.6 ± 0.40 mmol/l, TG 0.59 ± 0.15 mmol/l, LDL-C 0.70 ± 0.21 mmol/l and VLDL-C 0.12 ± 0.01 mmol/l; p < 0.001). The highest HDL-C levels were observed in the Asian mothers (1.60 ± 0.31 mmol/l vs. 1.4 ± 0.39 mmol/l in Greeks and 1.31 ± 0.39 mmol/l in Albanians; p < 0.001). Conclusion: The normal lipid profile in Greeks, the high one in Albanians and the low profile in Muslim Asians may be due to their nutritional habits and their socioeconomic status affecting those of their newborns.
Expression and Differential Effects of the Activation of Glucocorticoid Receptors in Mouse Gonadotropin-Releasing Hormone Neurons
Authors: Dondi Donatella , Piccolella Margherita , Messi Elio , Demissie Marek , Cariboni Anna , Selleri Silvia , Piva Flavio , Samara Athina , Consalez G. Giacomo , Maggi Roberto
Published: February 2006

Prenatal exposure of rodents to glucocorticoids (Gc) affects the sexual development of the offspring, possibly interfering with the differentiation of the hypothalamic-pituitary-gonadal axis. Glucocorticoid receptors (GR) are present on gonadotropin-releasing hormone (GnRH) neurons in the rat hypothalamus, suggesting a direct effect of Gc in the control of the synthesis and/or release of the hormone. In this study, we demonstrate the colocalization of immunoreactive GR with GnRH in a subpopulation of mouse hypothalamic GnRH neurons, confirming the possible involvement of Gc in mouse GnRH neuronal physiology. Receptor-binding assay, RT-PCR, immunocytochemistry, and immunoblotting experiments carried out in GN11 immortalized GnRH neurons show the presence of GR even in the more immature mouse GnRH neurons and confirm the expression of GR in GT1-7 mature GnRH cells. In GN11 cells, the activation of GR with dexamethasone produces nuclear translocation, but does not lead to the inhibition of GnRH gene expression already reported in GT1-7 cells. Long-term exposure of GN11 cells to dexamethasone induces an epithelial-like phenotype with a reorganization of F-actin in stress fibers. Finally, we found that Gc treatment significantly decreases the migratory activity in vitro and the levels of phosphorylated focal adhesion kinase of GN11 immature neurons. In conclusion, these data indicate that GR are expressed in mouse hypothalamic GnRH neurons in vivo as well as in the immature GN11 GnRH neurons in vitro. Moreover, the effects of the GR activation in GN11 and in GT1-7 cells may be related to the neuronal maturational stage of the two cell lines, suggesting a differential role of Gc in neuronal development.
Treating Auditory Hallucinations by Transcranial Magnetic Stimulation: A Randomized Controlled Cross-Over Trial
Authors: Jandl Martin , Steyer Juergen , Weber Martin , Linden David E.J. , Rothmeier Johannes , Maurer Konrad , Kaschka Wolfgang P.
Published: February 2006

Background: In a previous functional magnetic resonance imaging study, the authors succeeded in demonstrating the activation of Heschl’s gyrus during auditory hallucinations (AH). Objectives: This study aims to treat AH specifically by repetitive transcranial magnetic stimulation (rTMS). Methods: 16 patients with AH were included in a randomized, cross-over, sham-controlled trial. 1 Hz rTMS was administered over the left and right temporo-parietal cortex and sham position, respectively, on 5 consecutive days; 900 stimuli each, strength 100% of motor threshold. Using the Psychotic Symptom Rating Scales (PSYRATS), the hallucinations during the stimulation periods and 4-week follow-ups were quantified. Electroencephalograms (EEG) were acquired before and after each period. Results: Treatment responses were observed after left hemisphere rTMS only. The 5 patients who showed a response did so already after 2 days. However, group mean hallucination scores did not differ across treatment conditions. No significant changes were found in EEG after rTMS. Conclusions: A subgroup of patients suffering from AH benefits soon after treatment start from rTMS over the left superior temporal gyrus as revealed by the decrease of AH scores compared to right-sided and sham procedures.
Activation of the Prefrontal Cortex during the Wisconsin Card Sorting Test as Measured by Multichannel Near-Infrared Spectroscopy
Authors: Sumitani Satsuki , Tanaka Tsunehiko , Tayoshi Shin’Ya , Ota Koshi , Kameoka Naomi , Ueno Shu-ichi , Ohmori Tetsuro
Published: February 2006

Background:The Wisconsin Card Sorting Test (WCST) is a neuropsychological test to evaluate the function of the prefrontal cortex (PFC). However, inconsistent results have been reported concerning whether this task activates the PFC symmetrically or asymmetrically. Objectives:To investigate the brain activation in the PFC during the WCST, we examined blood oxygenation changes of healthy subjects by using multichannel near-infrared spectroscopy (NIRS). Methods:Subjects were 32 healthy volunteers, 18 males and 14 females. The WCST was administered using a computerized version, and the hemodynamic changes of the PFC during the WCST were measured by a 24-channel NIRS system.Results:A bilateral increase in oxygenated hemoglobin (oxyHb) was observed in the PFC in 20 subjects during the WCST. However, 5 subjects showed predominant activation on the left side and 3 subjects one on the right side. No oxyHb change was observed in 4 subjects, although they had good performances in the WCST. Conclusions:These results directly confirmed that the PFC was activated during the WCST in vivo by using the optical technique and suggested that the distribution of the activation in the PFC is different among healthy individuals.
Low Levels of α7-Nicotinic Acetylcholine Receptor mRNA on Peripheral Blood Lymphocytes in Schizophrenia and Its Association with Illness Severity
Authors: Perl Orly , Strous Rael D. , Dranikov Angela , Chen Rina , Fuchs Sara
Published: February 2006

Background: There is evidence that the nicotinic α7-acetylcholine receptor (α7-AChR) is involved in the pathophysiology of schizophrenia. Several neurotransmitter receptors, including α7-AChR, have been demonstrated on peripheral blood lymphocytes (PBL) and it has been suggested that these peripheral receptors may reflect corresponding brain receptors. Objective: In this study we compare α7 mRNA expression in PBL between schizophrenia patients and control individuals in order to determine whether any correlation exists between α7 mRNA expression in PBL and severity of schizophrenia. In addition, the isoforms of α7-AChR expressed are identified. Method: Peripheral venous blood samples were collected from individuals with schizophrenia (n = 44) and from healthy subjects (n = 16). Symptomatology and illness severity were assessed using standard clinical psychiatric evaluation scales. RNA was prepared from isolated lymphocytes and DELETE α7 mRNA was measured by RT-PCR. Results: We observed a significantly lower level of α7 mRNA on PBLs of schizophrenia patients incomparison with healthy controls (p < 0.00). A tendency to a negative correlation was noted between the CGI score, reflecting illness severity, and the α7-subunit gene expression. Conclusion: Observations confirm that the α7 mRNA in PBL represents the duplicated α7-AChR gene rather than the classic α7-AChR gene. Our study observations further substantiate the involvement of α7-AChR in the pathophysiology of schizophrenia and, while preliminary, indicate that the α7-AChR may be expressed and be readily measured in the peripheral blood circulation.
Lyme Disease: The Quest for Magic Bullets
Authors: Stricker Raphael B. , Lautin Andrew , Burrascano Joseph J.
Published: February 2006

Lyme disease represents a growing public health threat. Recent molecular and genetic studies have confirmed that Borrelia burgdorferi, the spirochetal agent of Lyme disease, is one of the most complex bacteria known to man. Affinity for multiple cell types and the presence of non-replicating forms of B. burgdorferi have contributed to persistent infection and failure of simple antibiotic regimens. The controversial clinical science of Lyme disease has impeded reliable diagnosis and effective treatment of this protean illness. Two major clinical hurdles are the absence of a therapeutic endpoint in treatingLyme disease and the presence of tick-borne coinfections that may complicate the course of the illness. New strategies for the diagnosis, treatment and prevention of Lyme disease are urgently needed.
Update of Alpha Fetoprotein Growth-Inhibitory Peptides as Biotherapeutic Agents for Tumor Growth and Metastasis
Authors: Mizejewski G.J. , Muehlemann M. , Dauphinee M.
Published: February 2006

The present update describes the biological activities of an alpha fetoprotein (AFP)-derived peptide termed the growth-inhibitory peptide (GIP), which is a synthetic 34-amino acid segment produced from the native molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult cells. Even though its mechanism of action has not been completely elucidated, GIP has been shown to engage in cellular events such as endocytosis, cellular aggregation, hemagglution, and cytoskeleton-induced cell shape changes. The GIP was shown to be growth-suppressive in nine different human tumor types and to suppress the spread of tumor infiltrates and metastases in human and mouse mammary cancers. It was further found that the oligomeric state (cyclic vs. linear configuration) of the GIP determined its biological and anticancer efficacy. The combined properties of tumor growth suppression and reduction of tumor metastases represent promising areas for GIP as a chemotherapeutic agent. It was concluded that the GIP derived from full-length AFP represents a growth-inhibitory motif possessing intrinsic properties that allow it to interact in cell surface events such as tumor proliferation, progression, and metastasis.
Maximum Skin Hyperaemia Induced by Local Heating: Possible Mechanisms
Authors: Gooding Kim M. , Hannemann Michael M. , Tooke John E. , Clough Geraldine F. , Shore Angela C.
Published: February 2006

Background: Maximum skin hyperaemia (MH) induced by heating skin to ≧42°C is impaired in individuals at risk of diabetes and cardiovascular disease. Interpretation of these findings is hampered by the lack of clarity of the mechanisms involved in the attainment of MH. Methods: MH was achieved by local heating of skin to 42–43°C for 30 min, and assessed by laser Doppler fluximetry. Using double-blind, randomized, placebo-controlled crossover study designs, the roles of prostaglandins were investigated by inhibiting their production with aspirin and histamine, with the H1 receptor antagonist cetirizine. The nitric oxide (NO) pathway was blocked by the NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME), and enhanced by sildenafil (prevents breakdown of cGMP). Results: MH was not altered by aspirin, cetirizine or sildenafil, but was reduced by L-NAME: median placebo 4.48 V (25th, 75th centiles: 3.71, 4.70) versus L-NAME 3.25 V (3.10, 3.80) (p = 0.008, Wilcoxon signed rank test). Inhibition of NO production (L-NAME) resulted in a more rapid reduction in hyperaemia after heating (p = 0.011), whereas hyperaemia was prolonged in the presence of sildenafil (p = 0.003). The increase in skin blood flow was largely confined to the directly heated area, suggesting that the role of heat-induced activation of the axon reflex was small. Conclusion: NO, but not prostaglandins, histamine or an axon reflex, contributes to the increase in blood flow on heating and NO is also a component of the resolution of MH after heating.
Expression of Melanocortin MC3 and MC4 Receptor mRNAs by Neuropeptide Y Neurons in the Rat Arcuate Nucleus
Authors: Mounien Lourdes , Bizet Patrice , Boutelet Isabelle , Vaudry Hubert , Jégou Sylvie
Published: February 2006

Neuropeptide Y (NPY) and α-melanocyte-stimulating hormone (α-MSH), two neuropeptides that are synthesized in neurons of the arcuate nucleus of the hypothalamus, exert opposite actions on food intake and body weight. NPY is orexigenic and decreases energy expenditure whereas α-MSH reduces food consumption and stimulates catabolism. α-MSH is an endogenous ligand for the central melanocortin receptors, MC3-R and MC4-R. In order to determine whether α-MSH may act directly on NPY neurons in the arcuate nucleus, we have investigated the possible occurrence of MC3-R and MC4-R mRNA in NPY-expressing cell bodies in the rat hypothalamus. Double-labeling in situ hybridization histochemistry using 35S-labeled (MC3-R or MC4-R) and digoxigenin-labeled (NPY) riboprobes revealed that 38 ± 1% of the NPY mRNA-positive perikarya expressed MC3-R mRNA while only 9 ± 2% of the NPY-producing neurons contained MC4-R mRNA. The proportions of NPY neurons that express MC3-R mRNA or MC4-R mRNA were not significatively different in the anterior and posterior aspects of the arcuate nucleus. The present study shows that a large proportion of NPY neurons in the rat hypothalamus express MC3-R mRNA while a much lower number of NPY neurons express MC4-R mRNA, suggesting that melanocortins may directly modulate the activity of the hypothalamic NPY system, mainly through activation of MC3-R. These data provide additional evidence for the complex interactions between the stimulatory (NPY) and inhibitory (α-MSH) pathways controlling feeding behavior and energy homeostasis.
Modulation and Redistribution of Proteinase Inhibitor 8 (Serpinb8) during Kidney Regeneration
Authors: Gillard Anneliese , Scarff Kate , Loveland Kate L. , Ricardo Sharon D. , Bird Phillip I.
Published: February 2006

Background: The intracellular serpin, proteinase inhibitor 8 (PI8/Serpinb8), can inhibit furin, a prohormone convertase involved in inflammation, prohormone processing and extracellular matrix remodeling. Unilateral ureteral obstruction (UUO) is a well-characterized model of kidney disease associated with interstitial fibrosis, where recovery involves cellular proliferation and extracellular matrix remodeling. Given the presence of mouse PI8 (mPI8) in kidney, the UUO technique was used to investigate its potential role in kidney disease and regeneration. Methods: RT-PCR and in situ hybridization was used to assess PI8 mRNA in kidney sections. Immunohistochemistry was used to examine mPI8 distribution in normal kidney, and following reversal of UUO. Results: mPI8 mRNA was detected in whole kidney by RT-PCR, and by in situ hybridization in convoluted tubules of the renal cortex and medulla. In normal and control contralateral unobstructed kidneys, mPI8 was within the ascending limb and convoluted section of the distal tubules. PI8 distribution did not change in UUO kidney, but was significantly altered in reversed UUO kidney, appearing in regions containing nephrons undergoing remodeling. These included regenerating proximal and distal tubules and glomeruli. Conclusions: mPI8 distribution alters during kidney regeneration, possibly to control a prohormone convertase involved in inflammation or tissue repair.
Advanced Oxidation Protein Products Accelerate Atherosclerosis Through Promoting Oxidative Stress and Inflammation
Authors: Liu Shang Xi , Hou Fan Fan , Guo Zhi Jian , Nagai Ryoji , Zhang Wei Ru , Liu Zhi Qiang , Zhou Zhan Mei , Zhou Mei , Xie Di , Wang Guo Bao , Zhang Xun
Published: February 2006

Objective—Increased level of plasma advanced oxidation protein products (AOPPs) has been found in patients with uremia and nonuremic subjects with coronary artery disease. This study was conducted to test the hypothesis that AOPPs play a causal role in atherosclerosis.

Methods and Results—Hypercholesterolemic (0.5% wt/wt diet) or normal rabbits received either repeated intravenous injections of AOPPs modified rabbit serum albumin (AOPPs-RSA) or unmodified RSA for 8 weeks. Compared with RSA- or vehicle-treated hypercholesterolemic rabbits, AOPPs-RSA–treated animals displayed increased atherosclerotic plaque area oxidized low-density lipoprotein (oxLDL) deposition, macrophage infiltration, and smooth muscle cell proliferation. Aortic sections from AOPPs-RSA–treated normal rabbits showed significant focal intima proliferation and mild Oil-Red-O staining lipid deposition in the affected areas, a phenomenon not observed in the RSA- or vehicle-treated controls. Plasma AOPPs levels in AOPPs-treated groups significantly increased in both hypercholesterolemic and normal rabbits compared with their relevant controls. Close correlations were found between plasma levels of AOPPs and the parameters of oxidative stress, eg, oxLDL and thiobarbituric acid reactive substances levels, or glutathione peroxidase activity. A highly significant correlation was also observed between plasma AOPPs and tumor necrosis factor (TNF)-α levels.

Conclusions—This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.
Lysophosphatidic Acid Induces Early Growth Response Gene 1 Expression in Vascular Smooth Muscle Cells
Authors: Cui Mei-Zhen , Laag Essam , Sun Longsheng , Tan Mingqi , Zhao Guojun , Xu Xuemin
Published: February 2006

Objective—

Lysophosphatidic acid (LPA), one component of oxidized low-density lipoprotein, is a potent bioactive phospholipid. Early growth response gene-1 (Egr-1), an important transcription factor, regulates expression of an array of genes involved in vascular diseases. Whether and how LPA regulates the transcriptional machinery of Egr-1 gene is unknown and is addressed in this study.

Method and Results—

We found that LPA markedly induces Egr-1 mRNA and protein in aortic smooth muscle cells (SMCs). RNA stability and nuclear run-on assays reveal that LPA-induced Egr-1 gene expression is controlled at the transcriptional level. Reporter gene analyses have shown that the −141 to +20 nt region of the Egr-1 promoter contains regulatory elements. Electrophoretic mobility shift assays reveal that the DNA-binding activities of both CREB and SRF to the CRE and SRE motifs of the Egr-1 promoter are markedly elevated in response to LPA. The increased binding activity depends on the phosphorylation of CREB and SRF. Luciferase assays of a series of deleted or mutated Egr-1 promoter-reporter gene constructs, along with dominant negative CREB transfection analysis revealed that the 2 CRE sites and the 2 proximal SRE sites in the Egr-1 promoter are required for maximal LPA-induced Egr-1 gene expression.

Conclusions—

Our data reveal that LPA regulates Egr-1 expression via transcription factors CREB and SRF. These results establish a novel role for CREB in mediating LPA-induced gene expression. Our results imply that elevated LPA levels may, through activation of Egr-1, which regulates an array of atherogenic genes, exacerbate atheromatous lesions.
Homocysteine Activates cAMP-response Element Binding Protein in HepG2 Through cAMP/PKA Signaling Pathway
Authors: Woo Connie W.H. , Siow Yaw L. , O Karmin
Published: February 2006

Objective—Hyperhomocysteinemia is an independent risk factor for cardiovascular disorders. Our previous studies demonstrated that hyperhomocysteinemia not only elicited inflammatory responses in the vascular endothelium but also induced fatty liver and hypercholesterolemia via transcriptional regulation. One of the transcription factors activated in the liver during hyperhomocysteinemia was cAMP-response element binding protein (CREB). CREB regulates the expression of many genes including those involved in lipid and glucose metabolism. In this study, we investigated the molecular mechanism by which Hcy activated CREB in rat liver and in hepatocytes (HepG2).

Method and Results—Hyperhomocysteinemia was induced in rats by feeding high-methionine diet for 4 weeks. There was a significant increase in hepatic cAMP levels, protein kinase A (PKA) activity and an activation of CREB. Incubation of HepG2 cells with Hcy (50 to 100 μmol/L) significantly enhanced CREB phosphorylation and subsequently increased CREB/DNA binding activity. PKA was activated in Hcy-treated cells as a result of increased cellular cAMP level. Inhibition of adenylyl cyclase not only reduced the intracellular cAMP levels elevated by Hcy treatment but also inhibited PKA activation and prevented Hcy-induced CREB phosphorylation.

Conclusion—These results suggest that the cAMP/PKA signaling pathway plays an important role in mediating Hcy-induced CREB activation in hepatocyte.