bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation in Chronic Venous Insufficiency: Is the Problem Insurmountable?
Authors: Takase Shinya , Delano Frank A. , Lerond Laurence , Bergan John J. , Schmid-Schönbein Geert W. 
Published: April 2003

One of the hallmarks of venous insufficiency is an elevated venous pressure. While a number of mechanisms have been proposed for vascular and parenchymal cell damage following venous pressure elevation, such as white cell infiltration, a key question remains as to what degree venous occlusion and flow interruption per se may constitute a risk factor in venous disease. To gain an insight into this mechanism, we examined the effect of venous occlusion followed by reperfusion. A draining venule (circa 50 µm) in the rat mesentery was occluded with a micropipette (1 h) followed by reperfusion (1 h). The procedure serves to raise the microvascular pressure to about 31 mm Hg during the occlusion while the flow is completely stopped in the local venous and capillary network. Parenchymal cell death in the mesentery was monitored by propidium iodide (PI) labeling. The number of PI-positive cells significantly increased predominantly during reperfusion. A 1-week treatment with a micronized purified flavonoid fraction (100 mg/kg/day) served to significantly reduce parenchymal cell death as well as leukocyte rolling, adhesion to postcapillary venule, and migration into the tissue both during occlusion and reperfusion. The results indicate, that even in an initially symptomless tissue, flow reduction combined with microvascular pressure elevation during venous occlusion results in tissue damage not only during reperfusion (as in arterial occlusion) but also during occlusion.
Adhesion Molecule Expression in Postischemic Microvascular Dysfunction: Activity of a Micronized Purified Flavonoid Fraction
Authors: Korthuis Ronald J. , Gute Dean C. 
Published: April 2003

Ischemia and reperfusion (I/R) induces neutrophil infiltration in skeletal muscle that is localized to the ischemic region. To transmigrate at ischemic regions, granulocytes must first arrest in the postcapillary venular segment of the microcirculation. Initially, leukocytes roll along the endothelium of these venules, a weak adhesive interaction that is mediated by the selectins (L-, E-, and P-selectin). Leukocyte rolling functions to slow the neutrophil during its transit through the microcirculation, thereby allowing it to monitor its local environment for the presence of activating factors arising from the ischemic tissues. When activated, the rolling granulocyte is rendered capable of forming the stronger adhesive interactions that allow the cell to become arrested in postcapillary venules in the ischemic region. These adhesive interactions are mediated by a leukocyte glycoprotein complex designated CD11/CD18 and intercellular adhesion molecule-1 (ICAM-1) expressed on endothelial cells. The stationary neutrophil uses the gradient in concentration of soluble chemoattractants liberated from ischemic tissues as a directional cue to move from the vascular to extravascular compartment, being guided in its transit across the endothelium by interactions with platelet endothelial cell adhesion molecule-1 (PECAM-1), an adhesive molecule localized to the interendothelial cleft. This paper reviews current understanding of the mechanisms underlying the establishment of leukocyte/endothelial cell interactions in postischemic skeletal muscle in terms of specific adhesion molecules that participate in neutrophil sequestration after I/R. Discovery of the molecular determinants of neutrophil/endothelial cell adhesion has uncovered potential mechanisms whereby agents exhibiting anti-adhesive properties may act. The micronized purified flavonoid fraction (450 mg diosmin, 50 mg hesperidin) prevents I/R-induced leukocyte adhesion in skeletal muscle. This anti-adhesive effect appears to be mediated at least in part by inhibition of induced expression of ICAM-1.
Pattern of Candidiasis in the Newborn: A Study from Kuwait
Authors: Al-Essa Mazen , Khan Ziauddin , Rashwan Nabil , Kazi Ahmed 
Published: April 2003

<i>Objectives:</i> To determine the rate and pattern of <i>Candida</i> infection in a large neonatal unit in Kuwait. <i>Methods:</i> A prospective study of all newborn infants who were admitted to the neonatal intensive care unit (NICU) at Maternity Hospital in Kuwait during the year of 1997 and who were suspected of having <i>Candida</i> infection were collected and analyzed. Method of selection of neonates, laboratory parameters and possible risk factors of the infection were identified and defined. <i>Results:</i><i>Candida</i> infection was recognized in 22 (8.4%) cases out of 263 total infants admitted to the NICU. All the proven cases originated from 168 infants of birth weight less than 2,000 g with an incidence of 13%. In addition, <i>Candida</i> infection was suspected and treated without positive culture in 15 infants (5.7%). Cases with proven <i>Candida</i> sepsis had longer mean duration of endotracheal intubation (p < 0.03) and total parenteral nutrition (p < 0.03) and more episodes of concomitant bacterial infection (p < 0.01) compared to infants with suspected candidiasis. <i>Conclusion:</i> For an early diagnosis of candidiasis, a high index of suspicion in septic low-birth weight infants is always warranted since the clinical and laboratory diagnostic parameters are difficult to differentiate between suspected and proven cases.
Glucocorticoid Regulation of Hypothalamic Proopiomelanocortin
Authors: Wardlaw Sharon L. , McCarthy Kieran C. , Conwell Irene M. 
Published: April 2003

Although glucocorticoids clearly inhibit proopiomelanocortin (POMC) gene transcription and peptide synthesis in the anterior pituitary, the effects of glucocorticoids on POMC in the hypothalamus are still unclear, even though most POMC neurons in the arcuate nucleus are known to have glucocorticoid receptors. In this study, we have therefore examined the effect of adrenalectomy (ADX) and glucocorticoid replacement on POMC mRNA and peptide (β-EP and α-MSH) levels in the medial basal hypothalamus (MBH) of the rat. POMC mRNA was measured by a sensitive solution hybridization S1 nuclease protection assay, and β-EP and α-MSH were measured by radioimmunoassay. In a first experiment, animals were studied 7 days after ADX or sham surgery. The mean POMC mRNA concentration was 1.01 ± 0.14 pg/µg RNA (means ± SE) in the intact animals and decreased to 0.55 ± 0.07 pg/µg RNA in the MBH of the ADX animals (p < 0.005). β-EP levels decreased in parallel from 4.30 ± 0.18 to 3.36 ± 0.11 ng/mg protein (p < 0.001); α-MSH levels decreased from 3.25 ± 0.21 to 2.41 ± 0.16 ng/mg protein (p < 0.005). In a second experiment, animals were studied 2 weeks after ADX. POMC mRNA levels again fell significantly from 1.15 ± 0.19 pg/µg RNA in the intact animals to 0.51 ± 0.06 pg/µg in the ADX animals (p < 0.01). β-EP levels fell also, but this was not significant. In a third experiment, all animals underwent ADX, and half of them received daily subcutaneous injections of dexamethasone (20 µg). Nine days after ADX, the mean POMC mRNA level was 0.66 ± 0.04 pg/µg RNA in the saline-treated animals and increased to 0.98 ± 0.08 pg/µg RNA in the dexamethasone-treated animals (p < 0.005). A parallel increase in β-EP levels from 5.03 ± 0.41 to 6.01 ± 0.53 ng/mg protein was also noted, but this was not statistically significant. We conclude that POMC gene expression is significantly inhibited in the MBH at 1 and 2 weeks after ADX. This effect was reversed by glucocorticoid replacement with doses close to the physiological range. The parallel changes in POMC mRNA and peptide levels strongly suggest that, in contrast to the anterior pituitary, low doses of glucocorticoids stimulate the biosynthesis of POMC in the MBH of ADX rats.
Blockade of the Oestrogen-Induced Luteinizing Hormone Surge in Ovariectomized Ewes by a Highly Selective Opioid µ-Receptor Agonist: Evidence for Site of Action
Authors: Walsh John P. , Clarke Iain J. 
Published: April 2003

Endogenous opioid systems in the hypothalamus inhibit gonadotropin-releasing hormone (GnRH) secretion, and a reduction in this inhibitory input (disinhibition) is thought to be part of the neural mechanism of the preovulatory GnRH/luteinizing hormone (LH) surge. We showed previously that intracerebroventricular infusion of the highly specific opioid µ-receptor agonist DAMGO delayed the oestrogen-induced LH surge in ovariectomized (OVX) ewes, whereas both δ- and ĸ-agonists were ineffective. The aim of the present study was to establish the anatomical site of this effect. The most likely hypothalamic sites of action are the medial preoptic area (MPOA), where most GnRH perikarya are located in sheep, and/or the median eminence (ME), where GnRH fibres terminate on hypophysial portal blood vessels. Conscious, unrestrained OVX ewes with permanent bilateral guide tubes implanted into either the MPOA or the mediobasal hypothalamus (MBH), close to the ME, were injected (im) with oestradiol benzoate (EB) 50 µg (t = 0 h). In this model, EB elicits a time-delayed surge in LH secretion after 13–19 h. Jugular venous blood was sampled at half-hourly intervals from –2 to 0 h, and from 10 to 26 h. From 12 to 20 h, bilateral infusions of either the highly specific opioid µ-agonist DAMGO (40 nmol/h bilaterally) or saline were given into the MPOA or MBH at 2.5 µl/h. Guide tube placements were confirmed histologically. The mean (± SEM) time to the onset of the LH surge was significantly (p < 0.01) increased in the animals (n = 9) that received DAMGO infusion into the MPOA (20.5 ± 1.4 vs. 15.7 ± 0.6 h in the saline-infused controls). The effect was clearly apparent in 6/9 of the DAMGO-infused animals. The mean (± SEM) time to LH surge onset was also significantly (p < 0.01) increased in the animals (n = 8) that received DAMGO infusion into the MBH (19.7 ± 1.2 vs. 14.3 ± 0.5 h). In this case, the effect was clearly apparent in 4/8 of the DAMGO-infused animals. We conclude that bilateral infusion of DAMGO into either the MPOA or the MBH can delay the EB-induced LH surge in OVX ewes. These data provide further evidence for dual hypothalamic sites of opioid regulation of GnRH secretion, and are consistent with the hypothesis that disinhibition from opioid tone at both the MPOA and MBH/ME is permissive of the preovulatory GnRH/LH surge.
Characterization of the Dopaminergic Input to the Pituitary Gland throughout the Estrous Cycle of the Rat
Authors: DeMaria Jamie E. , Livingstone John D. , Freeman Marc E. 
Published: April 2003

Changes in the concentrations of dopamine (DA) and its major metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were characterized in the pituitary gland throughout the 4-day estrous cycle of the rat. Female rats were sacrificed at 2- to 3-hour intervals throughout each day of the 4-day estrous cycle. Pituitary glands were removed, and the concentrations of DA and DOPAC were determined by high-performance liquid chromatography coupled to electrochemical detection. The concentration of prolactin (PRL) in serum from these same animals was determined by radioimmunoassay. The concentration of DA in the anterior lobe was constant throughout most of the 4-day estrous cycle. Prior to initiation of the proestrous surge of PRL, there were significant (p <0.05) decreases in the concentrations of both DA and DOPAC in the anterior lobe which returned to elevated baseline levels just prior to the termination of the proestrous surge of PRL. The concentrations of DA and DOPAC in the intermediate lobe exhibited a daily rhythm. However, in the intermediate as well as in the anterior lobe, there were significant (p < 0.001) decreases in the concentrations of both DA and DOPAC, coincident with the initiation of the proestrous surge of PRL. Similarly, coincident with the peak of the proestrous surge of PRL, there were significant (p < 0.001) increases in the concentrations of DA and DOPAC in the intermediate lobe, followed by a return to basal levels and resumption of the daily rhythm. The pattern of the concentrations of DA and DOPAC in the neural lobe was also daily in nature, with peaks occurring between 13.00 and 15.00 h each day of the 4-day estrous cycle. These data, taken together: (1) confirm that a decrease of the concentrations of DA and DOPAC occurs in the anterior lobe prior to the proestrous surge of PRL; (2) reveal that DA is released in a daily pattern at intermediate and neural lobes, and (3) suggest an apparent role for DA released to the intermediate lobe in the regulation of the proestrous surge of PRL.
Bromocriptine Reduces Obesity, Glucose Intolerance and Extracellular Monoamine Metabolite Levels in the Ventromedial Hypothalamus of Syrian Hamsters
Authors: Luo Shuqin , Meier Albert H. , Cincotta Anthony H. 
Published: April 2003

We examined whether reductions in body fat stores and insulin resistance in Syrian hamsters induced by bromocriptine are associated with reductions in daily norepinephrine (NE) and serotonin activities as indicated by their extracellular metabolite levels in the ventromedial hypothalamus (VMH). High levels of these monoamines within the VMH have been suspected to induce obesity and insulin resistance. Microdialysate samples from the VMH of freely moving obese male hamsters (BW: 208 ± 5 g) were collected hourly over a 25-hour period before bromocriptine treatment, during the first day of and after 2 weeks of bromocriptine treatment (800 µg/animal daily, i.p.), and body composition and glucose tolerance analyses were conducted before and after 2 weeks of treatments. The microdialysate samples were analyzed by HPLC for metabolites of serotonin: 5-hydroxy-indoleacetic acid (5-HIAA), NE: 3-methoxy-4-hydroxy-phenylglycol (MHPG), and dopamine: homovanillic acid (HVA). Bromocriptine treatment for 14 days significantly reduced body fat by 60% and areas under the glucose and insulin curves during a glucose tolerance test by 50 and 46%, respectively. Concurrently, extracellular VMH contents of 5-HIAA, MHPG, and HVA were reduced by 50, 29 and 66%, respectively (p < 0.05). Similarly, VMH 5-HIAA and MHPG contents were 48 and 44% less, respectively (p < 0.05), in naturally glucose-tolerant hamsters compared with naturally glucose-intolerant hamsters. Bromocriptine induced reductions of body fat, and improvements in glucose intolerance may result in part from its ability to decrease serotonin and NE activities in the VMH.
Food Deprivation Decreases mRNA and Activity of the Rat Dopamine Transporter
Authors: Patterson Terrell Ann , Brot Michelle D. , Zavosh Aryana , Schenk James O. , Szot Patricia , Figlewicz Dianne P. 
Published: April 2003

We have hypothesized that the midbrain dopamine (DA) neurons are a target for insulin action in the central nervous system (CNS). In support of this hypothesis, we have previously demonstrated that direct intracerebroventricular infusion of insulin results in an increase in mRNA levels for the DA reuptake transporter (DAT). In this study, 24- to 36-hour food deprivation was used as a model of decreased CNS insulin levels, to test whether DAT mRNA levels, DAT protein concentration or DAT functional activity would be decreased. DAT mRNA levels, assessed by in situ hybridization, were significantly decreased in the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) (77 ± 7% of controls, p < 0.05) of food-deprived (hypoinsulinemic) rats. Binding of a specific high-affinity DAT ligand (<sup>125</sup>I-RTI-121) to membranes from brain regions of fasted or free-feeding rats provided an estimate of DAT protein, which was unchanged in both of the major terminal projection fields, the striatum and nucleus accumbens (NAc). In addition, we utilized the rotating disk electrode voltametry technique to assess possible changes in the function of the DAT in fasting (hypoinsulinemic) rats. The V<sub>max</sub> of DA uptake was significantly decreased (87 ± 7% of control, p < 0.05), without a change in the K<sub>m</sub> of uptake, in striatum from fasted rats. In vitro incubation with a physiological concentration (1 n<i>M</i>) of insulin resulted in an increase of striatal DA uptake to control levels. We conclude that striatal DAT function can be modulated by fasting and nutritional status, with a contribution by insulin.
Effects of Diabetes and Estradiol on Norepinephrine Release in Female Rat Hypothalamus, Preoptic Area and Cortex
Authors: Karkanias George B. , Morales José C. , Etgen Anne M. 
Published: April 2003

These studies determined whether diabetes and estradiol treatment altered norepinephrine (NE) release from hypothalamus, preoptic area (POA), and cortical slices from ovariectomized (OVX) female rats. Animals were sacrificed 12 days after the onset of streptozotocin-induced diabetes and 48 h following vehicle or estradiol injection. Brain slices were preloaded with <sup>3</sup>H-NE, and release was evoked twice (S1 and S2) by electrical stimulation. Diabetes increased hypothalamic NE release during S1 regardless of the administration of vehicle or estradiol. Neither estradiol treatment nor diabetes alone affected NE release during S2 in the hypothalamus or POA. Estradiol treatment elevated NE release in the POA during S2 but only in diabetic animals. Moreover, estradiol elevated cortical NE release during S2 regardless of the presence or absence of disease. We also examined whether α<sub>2</sub>-adrenoceptor regulation of NE release was influenced by diabetes or hormone treatment. Enhancement of NE release by α<sub>2</sub>-adrenoceptor antagonism was evident in all 3 brain regions. However, α<sub>2</sub>-adrenoceptor regulation of NE release was unaffected by diabetes and hormone treatment. These findings suggest that diabetes alters NE release in the hypothalamus/POA of female rats. Additionally, this work identifies a novel action of estradiol to enhance stimulated NE release in the cortex of female rats.
Interaction between Leptin and Neuropeptide Y on in vivo Growth Hormone Secretion
Authors: Carro Eva , Seoane Luisa M. , Señaris Rosa , Considine Robert V. , Casanueva Felipe F. , Dieguez Carlos 
Published: April 2003

Leptin, the product of the <i>ob</i> gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Leptin has recently been shown to play a stimulatory role on GH secretion. The aim of the present study was to investigate whether leptin regulation of GH secretion was mediated by hypothalamic neuropeptide Y (NPY). We assessed the effect of leptin administration (10 µg, i.c.v.) and/or NPY (4 µg, i.c.v.) on fasted rats. Furthermore we administered leptin antiserum (10 µl, i.c.v.), anti-NPY serum (5 µl, i.c.v.) or normal rabbit serum (10 µl, i.c.v.) to freely moving fed rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. Fed rats treated with anti-NPY serum exhibited a normal ultradian GH rhythm. However, administration of anti-NPY serum (5 µl, i.c.v., at 120 min) completely reversed the suppression induced by antileptin serum (10 µl, i.c.v., at 0 min) on plasma GH levels (area under the curve, AUC, 168 ± 72 vs. 1,287 ± 430 ng/ml/6 h; p < 0.01). In fasted rats, following NPY administration, GH levels remained suppressed throughout the 6 h studied. Besides, NPY administration completely blunted leptin-induced GH secretion as assessed by the AUC (28.5 ± 11 vs. 520 ± 220 ng/ml/6 h; p < 0.01). Thus, it is possible that NPY mediates the effects of leptin on GH secretion. Alternatively, leptin and NPY could act through parallel pathways to alter GH release with NPY overcoming the stimulatory effect exerted by leptin on plasma GH levels.
Allopregnanolone-Induced Modification of Presynaptic Basal and K<sup>+</sup>-Induced [<sup>3</sup>H]-Norepinephrine Efflux from Rat Cortical Slices during the Estrous Cycle
Authors: Belmar Jorge , Cuellar Claudia , Llona Isabel , Arancibia Sandor , Kusch Claudia , Tapia-Arancibia Lucía , Pinter Albin , Pérez Hernán 
Published: April 2003

Superfused frontal slices of cerebral cortex were preloaded with [<sup>3</sup>H]-norepinephrine ([<sup>3</sup>H]NE). Basal [<sup>3</sup>H]NE efflux and K<sup>+</sup>-induced [<sup>3</sup>H]NE release were studied during the estrous cycle and in the presence of neurosteroids. Basal [<sup>3</sup>H]NE efflux showed estrous cycle-related variations, with lowest values found during estrus and diestrus II. Allopregnanolone (10<sup>–9</sup> <i>M</i>) potentiated basal [<sup>3</sup>H]NE efflux from the 1st minute of its application; the effect of the steroid was still present after 20 min. This effect was also dependent upon the estrous cycle, since basal [<sup>3</sup>H]NE efflux was mainly increased during estrus diestrus I, and to a lesser degree only during proestrus. During diestrus II and after ovariectomy, basal [<sup>3</sup>H]NE efflux was no longer affected by the neurosteroid. In the presence of yohimbine (10<sup>–6</sup> <i>M</i>), the effect of allopregnanolone on basal efflux was potentiated only during the first 3 min but vanished thereafter. Allopregnanolone (10<sup>–9</sup> <i>M</i>) potentiated the K<sup>+</sup>-induced [<sup>3</sup>H]NE release during estrus, but pregnenolone (10<sup>–9</sup> <i>M</i>) was ineffective, suggesting specificity of the neurosteroid. Yohimbine (10<sup>–6</sup> <i>M</i>) also potentiated K<sup>+</sup>-induced [<sup>3</sup>H]NE release. When applied simultaneously with allopregnanolone (10<sup>–9</sup><i>M</i>), a potentiating effect on [<sup>3</sup>H]NE release was observed. The present results suggest that allopregnanolone is a neurosteroid able to modulate norepinephrine release in the cerebral cortex in an estrous cycle-dependent manner, and that the effect could involve noradrenergic alpha-2 receptors.