bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation, Inhibition and Clearance of Plasmin in vivo
Authors: Chandler W.L. , Alessi M.C. , Aillaud M.F. , Vague P. , Juhan-Vague I. 
Published: April 2003

A 5 µg/kg bolus of tissue plasminogen activator (t-PA) was infused into 11 healthy subjects followed by measurement of t-PA activity and antigen, PAI-1 activity and antigen, t-PA/PAI-1 complex, plasmin/antiplasmin (PAP) complex and D-dimer over 4 h. Infusion of t-PA resulted in a rise in PAP levels in all subjects from a baseline of 2.4 ± 1.1 nmol/l to a peak of 5.1 ± 2.3 nmol/l, but had no effect on plasminogen, antiplasmin or D-dimer levels. Using a kinetic model of plasminogen activation in vivo, the second-order rate constant for t-PA binding to plasminogen was estimated to be 3,100 ± 1,300 mol<sup>–1</sup>l·s<sup>–1</sup>, 200–500 times slower than t-PA accelerated by fibrin. The half-life of PAP was 4.5 ± 1.6 h. In healthy subjects, the PAP level in plasma represents the average rate of plasminogen activation over the last 2–8 h.
Determination of Phylloquinone and Menaquinones in Food
Authors: Schurgers Leon J. , Vermeer Cees 
Published: April 2003

Fluctuations in international normalized ratio values are often ascribed to dietary changes in vitamin K intake. Here we present a database with vitamin K<sub>1</sub> and K<sub>2</sub> contents of a wide variety of food items. K<sub>1</sub> was mainly present in green vegetables and plant margarins, K<sub>2</sub> in meat, liver, butter, egg yolk, natto, cheese and curd cheese. To investigate the effect of the food matrix on vitamin K bioavailability, 6 healthy male volunteers consumed either a detergent-solubilized K<sub>1</sub> (3.5 µmol) or a meal consisting 400 g of spinach (3.5 µmol K<sub>1</sub>) and 200 g of natto (3.1 µmol K<sub>2</sub>). The absorption of pure K<sub>1</sub> was faster than that of food-bound K vitamins (serum peak values at 4 h vs. 6 h after ingestion). Moreover, circulating K<sub>2</sub> concentrations after the consumption of natto were about 10 times higher than those of K<sub>1</sub> after eating spinach. It is concluded that the contribution of K<sub>2</sub> vitamins (menaquinones) to the human vitamin K status is presently underestimated, and that their potential interference with oral anticoagulant treatment needs to be investigated.
High Glucose Levels Alter Angiotensin II-Induced Ca<sup>2+</sup> Uptake via PKC and cAMP Pathways in Renal Proximal Tubular Cells
Authors: Park Soo Hyun , Shin Sung Shik , Han Ho Jae 
Published: April 2003

Although a dysfunction of the calcium metabolism occurs in diabetes mellitus, alterations of Ca<sup>2+</sup> uptake induced by angiotensin II (ANG II) in renal proximal tubular cells (PTCs) grown in high-glucose medium are not fully elucidated. Thus, we examined whether high glucose concentrations can induce an alteration of the ANG II effect on the Ca<sup>2+</sup> uptake and its action mechanism in primary cultured renal PTCs. PTCs were exposed to different glucose concentrations (5–100 m<i>M</i>) and time intervals (0–48 h). There was a sustained increase of Ca<sup>2+</sup> uptake at glucose concentrations >15 m<i>M</i>. Thus, we selected 25 m<i>M</i> glucose and incubation for 48 h to maintain a hyperglycemic condition in vitro, unlike short-time regulatin. ANG II significantly inhibited the Ca<sup>2+</sup> uptake in a dose-dependent manner in a 5-m<i>M</i> glucose medium. In addition, downregulation of ANG II receptors appeared in a glucose dose dependent manner. However, PTCs treated with 25 m<i>M</i> glucose for 48 h, not 12 h, did not exhibit the inhibitory effect of ANG II (10<sup>–7</sup> <i>M</i>) on Ca<sup>2+</sup> uptake, although the inhibitory effect of ANG II on Ca<sup>2+</sup> uptake occurred in the presence of 25 m<i>M</i> mannitol or <i>L</i>-glucose. Staurosporine, bisindolylmaleimide I (protein kinase C, PKC, inhibitors), 12-<i>o</i>-tetradecanoylphorbol 13-acetate pretreatment, SQ 22536 (an adenylate cyclase inhibitor), and myristoylated protein kinase A inhibitor amide 14–22 (a protein kinase A inhibitor) blocked the 25-m<i>M</i>-glucose-induced alteration of ANG II effect on Ca<sup>2+</sup> uptake. These results suggest that both PKC and cyclic adenosine monophosphate (cAMP) pathways are involved in the high-glucose-induced alteration of ANG II effect on Ca<sup>2+</sup> uptake. Indeed, 25 m<i>M</i> glucose increased PKC activity and cAMP contents. In conclusion, a high glucose concentration altered ANG II induced inhibition of Ca<sup>2+</sup> uptake via PKC and cAMP pathways in the PTCs.
Effects of Pulsed High-Frequency Electromagnetic Fields on the Neuroendocrine System
Authors: Mann Klaus , Wagner Peter , Brunn Georg , Hassan Feisal , Hiemke Christoph , Röschke Joachim 
Published: April 2003

The influence of pulsed high-frequency electromagnetic fields emitted from a circularly polarized antenna on the neuroendocrine system in healthy humans was investigated (900 MHz electromagnetic field, pulsed with 217 Hz, average power density 0.02 mW/cm<sup>2</sup>). Nocturnal hormone profiles of growth hormone (GH), cortisol, luteinizing hormone (LH) and melatonin were determined under polysomnographic control. An alteration in the hypothalamo-pituitary-adrenal axis activity was found with a slight, transient elevation in the cortisol serum level immediately after onset of field exposure which persisted for 1 h. For GH, LH and melatonin, no significant effects were found under exposure to the field compared to the placebo condition, regarding both total hormone production during the entire night and dynamic characteristics of the secretion pattern. Also the evaluation of the sleep EEG data revealed no significant alterations under field exposure, although there was a trend to an REM suppressive effect. The results indicate that weak high-frequency electromagnetic fields have no effects on nocturnal hormone secretion except for a slight elevation in cortisol production which is transient, pointing to an adaptation of the organism to the stimulus.
Effect of Melatonin on 24-Hour Rhythms of Ornithine Decarboxylase Activity and Norepinephrine and Acetylcholine Synthesis in Submaxillary Lymph Nodes and Spleen of Young and Aged Rats
Authors: Cardinali Daniel P. , Brusco Luis I. , GarcíaBonacho Manuel , Esquifino Ana I. 
Published: April 2003

Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected with mycobacterial Freund’s adjuvant to produce an inflammatory disease of the joints and were studied the day before, and on days 6, 12 and 18 after injection. At every postinjection interval examined, old rats had significantly lower circadian amplitudes of pineal melatonin content. On day 18 of arthritis development, decreased levels of pineal melatonin were also seen in young rats. A second study, carried out 18 days after the injection of Freund’s complete adjuvant and after 17 daily injections of 10 or 100 µg of melatonin in the evening, indicated that melatonin treatment restored the inflammatory response in old rats (assessed plethysmographically in hind paws) to the level found in young animals. In young rats, an inflammation-promoting effect of 100 µg melatonin could be demonstrated. As a consequence of the immune reaction, submaxillary lymph node and splenic ornithine decarboxylase activity (an index of lymph cell proliferation) augmented significantly, with acrophases of 24-hour rhythms in the afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase activity (a presynaptic adrenergic marker) reached maximal values during early night hours while maximal values of [<sup>3</sup>H]acetylcholine synthesis (a presynaptic cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and mesor of these rhythms were lowest in old rats, an effect generally counteracted by melatonin treatment. The results suggest that inflammation is accompanied by an age-dependent, significant depression of pineal melatonin synthesis during adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of immune cell proliferation and autonomic activity in lymph nodes and spleen. These effects are counteracted by injection of melatonin, mainly in old rats.
Sprague-Dawley Rats Obtained from Different Vendors Exhibit Distinct Adrenocorticotropin Responses to Inflammatory Stimuli
Authors: Turnbull Andrew V. , Rivier Catherine L. 
Published: April 2003

The purpose of this work was to compare the plasma adrenocorticotropin (ACTH), corticosterone and interleukin-6 (IL-6) responses that rats of the outbred Sprague-Dawley strain obtained from two different vendors: Charles River (CR) and Harlan (HSD). Basal plasma ACTH and IL-6 concentrations were similar in rats from either vendor (HSD or CR), while CR animals exhibited slightly elevated corticosterone levels in late afternoon. Inflammatory stimuli such as lipopolysaccharide (LPS) (1 µg/kg, i.v.) or turpentine (50 µl/100 g, i.m.) which induce the production of endogenous cytokines, produced a significantly larger ACTH response in CR, compared to HSD rats, while the overall corticosterone responses were comparable in both rat groups. This could probably not be accounted for by a greater ACTH responsiveness in CR rats per se because CR and HSD rats showed similar peak ACTH responses to electrofootshock. Furthermore, in contrast to when the stimulus was one that induced endogenous cytokine production, the administration of exogenous interleukin-1β (IL-1β, 200 ng/kg, i.v.) produced a 2-fold greater rise in plasma ACTH concentrations in HSD rats compared to CR rats. The plasma IL-6 responses to the inflammatory stimuli showed a similar pattern to ACTH, with LPS and turpentine tending to pruduce greater IL-6 responses in CR rats, though these differences were not statistically significant. In contrast HSD rats had a significantly greater IL-6 response to IL-1β than did CR rats. Collectively, these results show that Sprague-Dawley rats obtained from different commercial sources can differ in immune-neuroendocrine responses to inflammatory stimuli.
Neuronal Elements in the Testis of the Rhesus Monkey: Ontogeny, Characterization and Relationship to Testicular Cells
Authors: Frungieri Monica B. , Urbanski Henryk F. , Höhne-Zell Barbara , Mayerhofer Artur 
Published: April 2003

Intrinsic neuron-like cells expressing the catecholamine-biosynthetic enzyme tyrosine hydroxylase (TH) were recently identified in the testis of the prepubertal rhesus monkey. In this study, we characterized the neuron-like nature of these cells and examined distribution and frequency of neuronal elements in the testes of monkeys during postnatal development, puberty and adulthood. Using immunohistochemical methods, we detected both nerve fibers and cell bodies, immunoreactive for the neuronal markers neurofilament 200 (NF-200) and synaptosomal associated protein of 25 kDa (SNAP-25), TH and neuropeptide Y (NPY) in perivascular locations, intermingled with interstitial cells and close to the wall of seminiferous tubules. Marked age-related differences in the numbers of these neuronal elements became apparent, when we quantified NF-200-immunoreactive neuronal elements. Thus, intrinsic neuron-like cell bodies were found only in the testes from immature animals (i.e., until about 3 years of age). Conversely, nerve fibers, presumably representing mainly the extrinsic innervation, were observed at all ages although they became more prominent after the pubertal increase in LH and testosterone levels. Interestingly, another testicular cell type known to contain potent regulatory substances, mast cells, was found to be in close anatomical proximity to nerve fibers. The number of these cells, positively identified with an antibody to tryptase, increased significantly after puberty following the same pattern as nerve fibers. These results confirm that the testicular nervous system of the monkey is composed of two components, intrinsic nerve cells and extrinsic fibers, both of which are catecholaminergic and peptidergic in nature. Furthermore, both components show a marked degree of plasticity during development, especially around the time of puberty. The intratesticular locations of neuron-like cells and fibers suggest that catecholamines and neuropeptides are likely to have multiple sites of actions, and may affect Leydig cells, cells of the tubular wall and vascular cells directly and/or indirectly via intermediation of mast cells.
Dopaminergic Agonists Normalize Elevated Hypothalamic Neuropeptide Y and Corticotropin-Releasing Hormone, Body Weight Gain, and Hyperglycemia in ob/ob Mice
Authors: Bina Keshavan G. , Cincotta Anthony H. 
Published: April 2003

Hypothalamic neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) influence feeding and levels of plasma glucose, insulin, free fatty acids, and triglycerides. Treatment of genetically obese, ob/ob mice, with dopamine receptor D<sub>1</sub>/D<sub>2</sub> agonists normalizes hyperphagia, body weight gain, hyperglycemia, and hyperlipidemia. We therefore examined whether levels of NPY and CRH immunoreactivity in discrete hypothalamic nuclei are altered in ob/ob mice, and whether dopaminergic treatment reverses this alteration. Female ob/ob mice were treated daily at 1 h after light onset with the D<sub>1</sub>/D<sub>2</sub> agonists, SKF-38393 (20 mg/kg) and bromocriptine (15 mg/kg), respectively or vehicle for 2 weeks. Such treatment, while normalizing body weight gain and hyperglycemia, also significantly reduced elevated NPY immunoreactivity in the suprachiasmatic (by 39%), intergeniculate (by 43%), paraventricular (PVN; by 31%), and arcuate (by 41%) nuclei in obese mice to levels observed in lean mice. This treatment also caused a 45–50% decline in levels of CRH in the PVN and dorsomedial hypothalamus compared to obese controls to levels observed in lean mice. Taken together, these findings suggest that dopaminergic D<sub>1</sub>/D<sub>2</sub> receptor coactivation may improve hyperphagia, hyperglycemia, and obesity in the ob/ob mouse, in part, by normalizing elevated levels of both NPY and CRH.
Recovery of the Hypothalamic-Pituitary-Adrenal Response to Stress
Authors: García Arantxa , Martí Octavi , Vallès Astrid , Dal-Zotto Silvina , Armario Antonio 
Published: April 2003

Pathological consequences of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may be related to the duration rather than to the intensity of HPA axis activation after exposure to the stressor. Consequently a fine analysis of post-stress events is of importance. The present experiments were designed to study the importance of three key factors in HPA recovery: intensity of the stressor (experiment 1), duration of exposure to the stressor (experiment 2) and previous experience of the animals with the situation (experiments 3 and 4). In experiment 1, analysis of both the response to the stressor and the poststress period showed that the stronger the stressor, the greater the area under the curve of HPA activation. In experiment 2, different groups of rats were exposed to different periods of immobilization (IMO) (20 min, 1 h and 2 h) and sampled before, during and after exposure to IMO. The speed of recovery of plasma corticotropin (ACTH) levels was not related to the duration of exposure to the stressor. In experiments 3 and 4, the influence of previous experience with the stressor was studied in rats daily exposed to 20 min IMO or daily injected with hypertonic saline (HS) for 8 days and sampled on days 1, 2, 5 and 8. Whereas a significant decline in plasma ACTH levels was not observed immediately after IMO until day 8, a single previous exposure to IMO was enough to enhance recovery 90 min after the end of exposure to IMO. Corticosterone levels were related to the number of previous experiences with the stressor only in the post-IMO period. In response to a novel stressor (forced swimming), chronic IMO rats showed a slightly impaired recovery as compared to stress-naive rats, suggesting that enhanced recovery of the HPA axis was specific for the homotypic stressor. After daily HS injections, a pattern similar to that after IMO was observed, the delayed, but not the early response of the HPA axis being reduced as a function of the number of previous experiences with the situation. Taken together, the present results suggest that the speed of recovery of the HPA axis after its activation by stressors is sensitive to the intensity of the stressors but not to their duration, and that adaptation to a repeated stressor is more apparent during the delayed HPA response.
Interactions of IGF-1 with the Blood-Brain Barrier in vivo and in situ
Authors: Pan Weihong , Kastin Abba J. 
Published: April 2003

Insulin-like growth factor-1 (IGF-1) given peripherally has been found effective in clinical trials to slow down neuronal degeneration in some nervous system diseases. This raises the question of whether and how IGF-1 crosses the blood-brain barrier (BBB). In this report, we found that IGF-1 had a half-life of 4.5 min in blood, could remain intact for 20 min, and entered brain and spinal cord linearly. In the brain, IGF-1 had an influx rate of 0.4 µl/g·min after intravenous (iv) bolus injection as determined by multiple-time regression analysis. Intact radiolabeled IGF-1 was present in brain at 20 min after iv injection. Most of the injected IGF-1 entered the brain parenchyma instead of being entrapped in the cerebral vasculature. Addition of nonradiolabeled IGF-1 enhanced the influx of radiolabeled IGF-1 after iv injection, but inhibited the influx of radiolabeled IGF-1 by in-situ brain perfusion, suggesting that protein binding can explain the difference between the iv and perfusion experiments. In the spinal cord, the cervical region had the fastest uptake, followed by lumbar spinal cord. The thoracic spinal cord had the slowest uptake, comparable to that of brain. By contrast, des(1-3)IGF-1, an IGF-1 analogue with little protein binding but similar biological activity, had a shorter half-life in blood, slower influx rate into brain, and no alteration in pharmacokinetics after addition of nonradiolabeled peptide. We conclude that IGF-1 enters the CNS by a saturable transport system at the BBB, which functions in synchrony with IGF binding proteins in the periphery to regulate the availability of IGF-1 to the CNS.
Estrogen Increases Angiotensin II-Induced c-Fos Expression in the Vasopressinergic Neurons of the Paraventricular Nucleus in the Female Rat
Authors: Kisley Lori R. , Sakai Randall R. , Flanagan-Cato Loretta M. , Fluharty Steven J. 
Published: April 2003

Previous studies in female rats have shown that estrogen treatment attenuates angiotensin II (AngII)-induced water intake. The mechanism underlying this attenuation may be decreased responsiveness to AngII, as revealed by a reduction in AngII binding to the angiotensin type 1 (AT<sub>1</sub>) receptor in the subfornical organ (SFO). It has not been determined whether these changes in receptor binding translate into changes in neuronal activity that, in turn, may influence behavior. Therefore, an estrogen-modulated change in neuronal pathways relevant to AngII-induced water intake was tested in ovariectomized (OVX) female rats using immunohistochemistry for the immediate early gene c-Fos as a marker for neuronal activation. Third cerebroventricular injection of AngII (6 ng) induced intense c-Fos immunoreactivity in forebrain regions associated with fluid intake, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, the SFO, the supraoptic nucleus and the paraventricular nucleus (PVN). Forty-eight-hour estradiol (10 µg) administration to OVX female rats increased AngII-induced c-Fos labeling in the lateral magnocellular neurons of the PVN by 30% as compared to vehicle-treated controls. Double labeling neurons in the PVN with c-Fos and either vasopressin or oxytocin antisera revealed that estrogen increased AngII-induced c-Fos expression by 28%, specifically in vasopressinergic neurons. Such changes in neuronal activation may explain the estrogen modulation of AngII-induced water intake that has been previously reported; it may be due to increased water retention to maintain plasma osmolality or to induction of a pressor response.
A Short Period of Maternal Nutrient Restriction in Late Gestation Modifies Pituitary-Adrenal Function in Adult Guinea Pig Offspring
Authors: Lingas Rania I. , Matthews Stephen G. 
Published: April 2003

Altered fetal environment can program the hypophyseal-pituitary-adrenal (HPA) axis development and thus affect endocrine function in later life. We hypothesized that 48 h of maternal nutrient restriction during the period of maximal fetal brain growth alters HPA function in adult offspring and leads to modified blood pressure regulation. Pregnant guinea pigs (n = 15) were deprived of food (water ad libitum) or fed normally (n = 13) on days 50 and 51 of gestation, after which they were all fed normally (birth = 68 days). Carotid artery and jugular vein catheters were implanted in adult guinea pig offspring (day 65). Animals were treated with corticotropin (ACTH<sub>1–24</sub>; 0.5 µg/kg), corticotropin-releasing hormone (CRH; 0.5 µg/kg) and insulin (5 units/kg), and pituitary-adrenal responses were measured. Guinea pigs were then euthanized and pituitaries removed for analysis of pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels. There was no effect of prenatal treatment on body weight, blood pressure or heart rate. In male offspring, both basal ACTH (p < 0.007) and basal cortisol (p < 0.05) levels were significantly reduced in animals whose mothers had been nutrient restricted (NR). In contrast, in female offspring, basal plasma ACTH was not different between offspring from NR mothers and controls; however, basal plasma cortisol concentrations were significantly (p < 0.01) elevated at 13.00 h in females born to NR mothers. Responses to HPA challenge were different between offspring from NR mothers and control offspring, and these differences were consistent with alterations in basal adrenocortical function. There was no effect of prenatal treatment on POMC mRNA levels in the pars distalis or pars intermedia. However, GR mRNA levels were significantly (p < 0.05) reduced in adult female offspring born to NR mothers. In conclusion, 48 h of maternal nutrient restriction during pregnancy has a long-term effect on HPA function in adult offspring, and this effect is highly sex specific, but does not result in alteration of blood pressure.