bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Efficacy of Micronized Purified Flavonoid Fraction: An Overview
Authors: Struckmann Jan R. 
Published: April 2003

Flavonoids are widely used for the treatment of chronic venous insufficiency (CVI). In clinical trials, micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin, Daflon 500 mg) has demonstrated its activity in CVI by improving venous tone and vein elasticity assessed by plethysmography. Randomized, double-blind, placebo-controlled clinical studies have shown an improvement in signs and symptoms related to CVI and a decrease in leg circumferences at the levels of the ankle and calf. The effect of MPFF on microcirculatory parameters suspected of participating in the pathophysiological process of venous ulceration has been investigated in patients. These include hemorheological parameters and transcutaneous oxygen tension measurements, which were shown to improve after treatment with MPFF. Finally, a randomized double-blind, placebo-controlled clinical study has shown that MPFF treatment for 2 months, in addition to standard compression therapy, accelerates leg ulcer healing in patients with ulcers ≤10 cm.
Enhanced Cutaneous Lymphatic Network in the Forearms of Women with Postmastectomy Oedema
Authors: Mellor R.H. , Stanton A.W.B. , Azarbod P. , Sherman M.D. , Levick J.R. , Mortimer P.S. 
Published: April 2003

Postmastectomy oedema (PMO) of the arm is a common aftermath of axillary lymphatic damage during treatment for breast cancer. The aim of the present study was to quantify the forearm dermal lymphatic capillaries in order to determine whether they exhibit adaptive responses to PMO. Both forearms were examined by fluorescence microlymphography in 16 patients with oedema following treatment for breast cancer (mean swelling 25 ± 4%) and 19 patients treated for breast cancer but without oedema. Delineated lymphatic networks were analysed stereologically. The main findings were: (1) lymphatic density at any specified distance from the injection site was greater in the swollen arm than the control arm (p < 0.01, t test); (2) taking into account the increased skin area, the total length of lymphatic capillaries in a 1-cm annulus of skin was 676 ± 56 cm (swollen), compared with 385 ± 30 cm (control) (p < 0.001, t test); (3) fluorescent marker was transported over a greater distance before draining deep in the swollen arm (2.74 ± 0.33 cm) than in the control arm (1.59 ± 0.24 cm) (p = 0.02); (4) there was no evidence of lymphatic dilatation in the swollen arm, and (5) in breast cancer patients without swelling, the arm on the side of radiotherapy/surgery (otherwise referred to as the unswollen arm) showed none of the above changes, indicating that the changes are linked to the oedema rather than being universal responses to breast cancer or its treatment. It is concluded that microlymphatic changes occur in the swollen arm, namely a local superficial rerouting of lymph drainage and either lymphangiogenesis and/or increased recruitment of dormant lymphatic vessels. Since blood capillary angiogenesis occurs in the swollen arms, and lymphangiogenesis occurs in experimental lymphoedema, there is a precedent for proposing lymphangiogenesis in PMO. An increased number of functional vessels would help to maintain the ratio of local tissue drainage capacity to filtration capacity.
Pathophysiology of Cyclosporine-Induced Nephrotoxicity in Humans: A Role for Nitric Oxide?
Authors: Gossmann Jan , Radounikli Androniki , Bernemann Alexander , Schellinski Oliver , Raab Hans-Peter , Bickeböller Ralf , Scheuermann Ernst-Heinrich 
Published: April 2003

<i>Background:</i> The causes for the nephrotoxicity of cyclosporine A (CsA) have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals, have been proposed. <i>Methods:</i> We studied prostaglandin metabolites, endothelin and nitric oxide in kidney transplant patients receiving their first CsA dose. Prostaglandin metabolites in the urine and endothelin and nitric oxide (NO<sub>2</sub>/NO<sub>3</sub>) in urine and plasma were measured in 14 patients before and 3 and 6 h after oral ingestion of CsA (10 mg/kg b.w.). Clearances for inulin and <i>p</i>-aminohippuric acid (PAH) were measured before and in two separate 3-hour periods after CsA. Blood pressure, heart rate, and CsA blood levels were also determined. <i>Results:</i> Clearances of inulin and PAH decreased progressively after CsA dosage while renal vascular resistance increased. Nitric oxide plasma levels decreased in nearly all patients from 21.0 ± 2.8 to 19.1 ± 2.6 (p = 0.003) and then rose slightly to 19.5 ± 2.5 µmol/l (p = 0.1) 3 and 6 h after CsA ingestion, respectively. Urinary excretion of NO<sub>2</sub>/NO<sub>3</sub> decreased nonsignificantly from 269 ± 38.8 to 259 ± 27.7 and 254 ± 41.6 µmol/min (p = 0.5 and 0.5). At the same time, urinary prostaglandin E<sub>2</sub> and 6-keto-prostaglandin F<sub>1α</sub> excretion rate declined significantly [from 1,187 ± 254 to 1,186 ± 351 and 730 ± 148 pg/min (p = 0.27 and 0.02) and from 697 ± 115 to 645 ± 134 and 508 ± 58.2 pg/min (p = 0.34 and 0.05)]. Urinary thromboxane B<sub>2</sub> and plasma and urinary endothelin first increased and then decreased nonsignificantly. Mean arterial pressure rose from 107 ± 2.5 to 110 ± 2.6 and 114 ± 3.4 mm Hg (p = 0.1 and 0.05). <i>Conclusion:</i> The pathophysiology of CsA-induced acute renal vasoconstriction involves several different mechanisms including a decrease of the vasodilating prostaglandins E<sub>2</sub> and 6-keto-prostaglandin F<sub>1α</sub> and possibly nitric oxide.
A 3-Year Retrospective Study of Community-Acquired Pneumonia in Kuwait with Emphasis on Microbial Aetiology
Authors: Awadh-Behbehani Nasser , Bitar Zuhair , Al-Enezi Fatima , Al-Mutairi Sana , Al-Azemi Mohamed , Al-Sayeq Faisal 
Published: April 2003

<i>Background:</i> There has not been any published study on community-acquired pneumonia (CAP) in Kuwait. The aim of this study is to determine the clinical characteristics of adult patients with CAP as well as the microbial aetiology and the treatment of CAP. <i>Methods:</i> A retrospective study of all CAP cases admitted to the three acute care hospitals in Kuwait over a 3-year period, 1993–1995, was done. <i>Results:</i> There were 290 patients identified, mean age 41 ± 19 years, of which 57% were males. The patients were divided into three groups (mild, moderate and severe) according to standard published criteria: mild 27.5%, moderate 61%, and severe 11.5%. The microbial aetiology was identified for only 15% of the total cases, 11.5% of the mild group, 14% of the moderate, and 22.5% of the severe. The most common organisms identified were <i>Streptococcus pneumoniae</i> 32%, <i>Mycoplasma pneumoniae</i> 20%, <i>Haemophilus influenzae</i> 14%, <i>Mycobacterium tuberculosis</i> 11%, gram-negative organisms other than Haemophilus species 11% and others 12%. There were 243 (84%) patients who received a single antibiotic as initial therapy while the rest received a combination of antibiotics. The most common antibiotics used were macrolide 28%, ampicillin 24%, a combination of antibiotic 17%, third-generation cephalosporin 12% and others 19%. <i>Conclusion:</i> The rate of identification of microbial aetiology in CAP is poor in Kuwait. There are 27.5% of the patients who can be classified as mild and probably the majority of them can be treated as out-patients. Based on these results, we have started a prospective study to better evaluate the microbial aetiology of CAP in Kuwait.
Endotoxin Induces Interleukin-1β and Nitric Oxide Synthase mRNA in Rat Hypothalamus and Pituitary
Authors: Satta Maria Antonia , Jacobs Richard Anthony , Kaltsas Gregory Athanasios , Grossman Ashley Barry 
Published: April 2003

The gases nitric oxide (NO) and carbon monoxide (CO) may be involved in hypothalamo-pituitary-adrenal axis (HPA) modulation. In the brain, NO is synthesized by two forms of NO synthase (NOS), a constitutive neuronal form (nNOS) and an inducible form (iNOS). There are also a constitutive heme oxygenase (HO<sub>2</sub>) and an inducible form (HO<sub>1</sub>) which generate CO. We have therefore investigated the effect of peripheral lipopolysaccharide (LPS) administration on the gene expression of these enzymes along with interleukin-1β (IL-1β) gene expression in the hypothalamus, pituitary and liver. Male Wistar rats (200–250 g body weight) were injected intraperitoneally with endotoxin (<i>Escherichia coli</i>, 055 B5) dissolved in sterile normal saline [250 µg/kg first group, 2.5 mg/kg (second group) and 6.25 mg/kg (third group)] in a final volume of 0.5 ml, or saline alone in the control group. The first and the second groups were studied 1, 3, 8 and 24 h after LPS (n = 4 per group); the third group was studied at 3 h. Total RNA was extracted from the hypothalamus, pituitary and liver, and cDNA was made using standard reverse transcriptase methods. Duplex polymerase chain reaction (PCR) was standardised in order to quantify the expression of a specific gene in relation to the ‘house-keeping’ gene β-actin. The specific genes studied were iNOS, nNOS, HO<sub>1</sub>, HO<sub>2</sub> and IL-1β. The PCR products were separated on agarose gel and densitometric analysis of the bands allowed semi-quantification. In the second group, iNOS and IL-1β were induced in hypothalamus, pituitary and liver, showing a peak at 3 h (p < 0.001), returning to baseline levels at 24 h. Neuronal NOS was not expressed in the liver under basal conditions or after LPS; in the hypothalamus and pituitary, nNOS was expressed basally but there was no change after LPS. In the first group, iNOS and IL-1β were again induced in all three tissues studied, but with a delayed time course compared to the second and third groups; the peak change for IL-1β occurred at 8 h (p < 0.05), again returning to baseline levels at 24 h. The peak for iNOS occurred at 24 h. HO<sub>1</sub> and HO<sub>2</sub> were expressed in all three tissues under basal conditions; HO<sub>1</sub> was increased at 1 h in the liver in the second group, and at 3 h in the pituitary in the third group. There was no change in either HO<sub>1</sub> or HO<sub>2</sub> in the hypothalamus at any dose at any time point. We conclude that IL-1β and iNOS are induced in rat hypothalamus and pituitary following various doses of endotoxin. We speculate that while IL-1β may mediate stimulation of the HPA by endotoxin, NO generation may be involved in the counter-regulation of this response.
Role of Corticotropin-Releasing Hormone in Gastrin-Releasing Peptide-Mediated Regulation of Corticotropin and Corticosterone Secretion in Male Rats
Authors: Garrido Margarita M. , Martin Sonsoles , Ambrosio Emilio , Fuentes José A. , Manzanares Jorge 
Published: April 2003

Gastrin-releasing peptide (GRP) exerts several functions within the hypothalamus and may be involved in the regulation of pituitary hormone secretion. The purpose of this study was to investigate the central effect of GRP on hypothalamic-pituitary-adrenal axis activity in the male rat. Intracerebroventricular (i.c.v.) but not intravenous administration of GRP (1, 10, 100 ng/rat) increased plasma ACTH and corticosterone concentrations in a dose-dependent manner. The highest dose (100 ng/rat) of GRP increased plasma ACTH and corticosterone 4- and 14-fold, respectively. This increase peaked at 30–60 min after i.c.v. injection, decreased gradually and returned to baseline levels 240 min after GRP administration. The i.c.v. administration of (Leu<sup>13</sup>-ψ-CH<sub>2</sub>NH-Leu<sup>14</sup>) bombesin, a competitive and specific GRP receptor antagonist, had no effect on ACTH and corticosterone secretion; however, a dose of 1 µg/rat completely blocked the increase of both hormones induced by GRP (10 ng). By using α-helical (9–41) corticotropin-releasing factor (CRF), a competitive antagonist of CRF, the role of CRF on GRP-induced ACTH and corticosterone secretion was also explored. α-Helical (9–41) CRF (10 µg/rat) blocked the increase in ACTH and corticosterone secretion induced by GRP (10 ng). The results obtained in this study suggest that GRP increases the secretion of ACTH and corticosterone in the plasma by acting centrally on GRP receptors, and that endogenous GRP receptor ligands do not tonically regulate ACTH and corticosterone secretion. Furthermore, the hypothalamus-pituitary-adrenal-activating effects induced by GRP appear to be mediated, at least in part, by CRF.
Inhibin Suppresses in vivo Growth Hormone Secretion
Authors: Carro Eva , Señarís Rosa M. , Mallo Federico , Diéguez Carlos 
Published: April 2003

Although the effects of inhibin on gonadotropin synthesis and secretion have been extensively studied, the role of inhibin in the neuroregulation of in vivo growth hormone (GH) secretion still remains to be elucidated. In the present work, we investigated the effects of inhibin on spontaneous GH secretion in three different groups of conscious adult male rats: intact, gonadectomized, and dihydrotestosterone (DHT)-treated gonadectomized animals. We found that inhibin administration (100 µg/kg, i.v.) led to a marked suppression in spontaneous GH secretion in all the groups studied. This significant decrease was assessed by the area under the curve in intact (311.1 ± 163.3 vs. 3,882.1 ± 1,084.6 ng/ml/6 h, p < 0.01), gonadectomized (416.6 ± 120.9 vs. 2,078.5 ± 298.4 ng/ml/6 h, p < 0.01) and gondadectomized rats treated with DHT (755.0 ± 102.3 vs. 4,539.3 ± 1,670.6 ng/ml/6 h, p < 0.01). Furthermore, intravenous inhibin significantly reduced in vivo GH responses to GHRH (10 µg/kg, i.v.) in both intact and gonadectomized rats. These findings suggest a role of inhibin on in vivo GH secretion in the male rat.
Potassium Channel Blockers Have Minimal Effect on Repolarization of Spontaneous Action Potentials in Rat Pituitary Lactotropes
Authors: Sankaranarayanan Sethuraman , Simasko Steven M. 
Published: April 2003

Patch-clamp techniques were used in primary cultures of rat lactotropes and the rat pituitary clonal cell line GH3 to determine the population characteristics of spontaneous action potentials and the nature of the currents responsible for repolarization of spontaneous action potentials. Spontaneous action potentials were observed in 75% of lactotropes (74/99) and 80% of GH3 cells (42/51). Lactotropes exhibited broad and shallow action potentials (average duration 460 ms, peak –17 mV, slope of upstroke 0.5 mV/ms) compared to the GH3 cells which displayed narrow and tall action potentials (average duration 177 ms, peak –10 mV, slope of upstroke 1.6 mV/ms). Blockers of potassium currents were used to determine the role of specific potassium currents in the repolarization process. Spontaneous action potentials in lactotropes were largely unaffected by 4-aminopyridine (4AP), charybdotoxin, and apamin. Tetraethylammonium (TEA) caused only an small increase in peak amplitude and, in a subset of cells, a small increase in duration. In contrast, in GH3 cells, TEA, 4AP, charybdotoxin, and apamin all caused a significant increase in duration, while TEA and charybdotoxin also caused an increase in peak amplitude. Further, apamin caused a positive shift in the afterhyperpolarization voltage. In lactotropes, strong buffering of intracellular calcium with calcium chelators (EGTA or BAPTA) caused a profound increase in action potential duration. Thus, repolarization of action potentials in lactotropes is a calcium-dependent process, but unlike GH3 cells, is not mediated by calcium-dependent potassium currents, nor is it strongly influenced by voltage-dependent potassium currents.
The in vitro Effect of Leptin onBasal and Growth Hormone-Releasing Hormone-StimulatedGrowth Hormone Secretion from theOvine Pituitary Gland
Authors: Roh Sang-Gun , Clarke Iain J. , Xu Ru-Wei , Goding James W. , Loneragan Kylie , Chen Chen 
Published: April 2003

We have studied the direct effect of leptin on the secretion of GH from the anterior pituitary gland of the sheep. Using primary cultures of ovine pituitary cells, leptin (10<sup>–9</sup>–10<sup>–7</sup> <i>M</i>) treatment for 30 min did not affect basal or GHRH (10<sup>–7</sup> <i>M</i>)-stimulated GH secretion. Following treatment for 24 h, a dose of 10<sup>–7</sup> <i>M</i> leptin stimulated basal GH secretion. In contrast, doses of 10<sup>–7</sup> and 10<sup>–8</sup> <i>M</i> leptin inhibited GHRH-stimulated GH secretion after 24 h of treatment. These results suggest that leptin can have long-term effects on the somatotropes, but no acute effect. Furthermore, leptin appears to have opposite effects on basal and GHRH-stimulated GH secretion.
Ontogeny of the Diurnal Rhythm of Tuberoinfundibular Dopaminergic Neuronal Activity in Peripubertal Female Rats: Possible Involvement of Cholinergic and Opioidergic Systems
Authors: Shieh Kun-Ruey , Pan Jenn-Tser 
Published: April 2003

The ontogeny of the diurnal change of tuberoinfundibular dopaminergic (TIDA) neuronal activity in female rats and its control mechanism were the foci of this study. Intact pre (28- and 35-day-old)-, peri (39- and 42-day-old)- and post (49- and 56-day-old)-pubertal female, as well as pre (28-day-old)- and post (56-day-old)-pubertal male Sprague-Dawley rats were used. Basal TIDA neuronal activity, determined by measuring 3,4-dihydroxyphenylalanine or 3,4-dihydroxyphenylacetic acid in the median eminence, increased 3- to 4-fold in the female and less than 2-fold in the male rats from day 28 to 49; so did serum prolactin levels. The diurnal rhythm of TIDA neuronal activity was not evident until day 42 in the female, but not male, rats. Neither nigrostriatal, nor mesolimbic DA neurons exhibited any significant change between pre- and postpubertal stages. In postpubertal (56-day-old) female rats, injection of nicotine (10 µg/kg) in the morning, but not in the afternoon, inhibited TIDA neuronal activity while similar injections of mecamylamine (1 mg/kg) or naloxone (2.5 mg/kg) stimulated these neurons in the afternoon, but not in the morning. Serum prolactin levels changed accordingly. In contrast, none of the injections had any effect in prepubertal (28-day-old) female rats. These results indicate that the genesis of the diurnal rhythm of TIDA neuronal activity in female rats occurs during the peripubertal stage, and endogenous cholinergic and opioidergic neurons may play a significant role.
Estrogens Normalize the Hypothalamic- Pituitary-Adrenal Axis Response to Stress and Increase Glucocorticoid Receptor Immuno- reactivity in Hippocampus of Aging Male Rats
Authors: Ferrini Monica , Piroli Gerardo , Frontera Miriam , Falbo Andrea , Lima Analia , De Nicola AlejandroF. 
Published: April 2003

Aging is associated with a disturbance in the regulation of the hypothalamic-pituitary-adrenal axis (HPA) and reduced levels of glucocorticoid receptors (GR) in the hippocampus. To compensate for these effects, we have investigated whether estrogen therapy normalized the HPA response to stress and GR in hippocampus and paraventricular (PVN) nucleus. Young (3–4 months) and old (20 months) male Sprague-Dawley rats were bled by tail cut in the basal state and following ether stress. While basal and ether-stimulated levels of plasma corticosterone (CORT) were similar in the two groups, old animals presented a delayed termination of the response to ether stress. A dexamethasone inhibition test carried out in old animals, showed a failure to completely block plasma CORT after ether stimulation. Furthermore, in old rats GR-immunoreactive levels were reduced in CA1-CA2 hippocampal subfields and subiculum, while normal levels were obtained in CA3-CA4 and PVN. We observed that prolonged estrogen treatment (6 weeks) of old rats normalized the termination of the stress response, restored dexamethasone inhibition of plasma CORT, and increased GR immunoreactivity in CA1 and CA2 hippocampal subfields and subiculum. The results suggest that estrogen treatment enhanced the glucocorticoid feedback signal by increasing GR in hippocampus, and corrected the disturbances in HPA axis regulation. These animal experiments may be important to elucidate the effects of estrogenic on the hippocampal and HPA dysfunction associated with aging and Alzheimer’s disease in humans.
Changes in Hypothalamic Estrogen Receptor-Containing Cell Numbers in Response to Feed Restriction in the Female Lamb
Authors: Hileman Stanley M. , Lubbers Laura S. , Jansen Heiko T. , Lehman Michael N. 
Published: April 2003

The mechanism whereby undernutrition enhances the ability of estradiol (E) to inhibit reproductive activity is unknown. This study aimed to determine the effect of feed restriction on E receptor (ER)-containing cell numbers in the female sheep hypothalamus. Ovariectomized lambs at 7 months of age received either ad libitum (AL; n = 5) or restricted (FR; n = 10) levels of feed intake. Lambs were weighted weekly and FR lambs fed to lose approximately 15% of their initial body weights over 7 weeks, at the end of which jugular blood samples were collected at 10-min intervals for 5 h to assess the patterns of LH release. After blood collection, lambs were euthanized and hypothalami collected for immunocytochemical detection of ER. Based on LH secretory profiles, FR lambs were subdivided into two groups. The first group (FR + LH; n = 5) exhibited patterns of LH release similar to AL controls. LH secretion in the second group (FR-LH; n = 5) was obviously suppressed. Numbers of ER-containing cells did not differ significantly (p > 0.10) among treatment groups in the bed nucleus stria terminalis, anterior hypothalamic area and arcuate nucleus. ER-containing cell numbers were greater (p < 0.05) in the preoptic area (POA) but less (p < 0.05) in the ventromedial/ventrolateral hypothalamus (VMH/VLH) for FR-LH lambs compared to AL animals. Notably, for both the POA and VMH/VLH, ER-containing cell numbers in the FR + LH animals were intermediate and did not differ (p > 0.10) from either FR-LH or AL lambs. These results suggest that feed restriction differentially alters ER-containing cell numbers in specific regions of the ovine hypothalamus (numbers increased in the POA but decreased in the VMH/VLH). These changes may, at least in part, represent a mechanism whereby undernutrition enhances the ability of E to inhibit reproduction.
Thyroid Hormones Regulate the Expression of Somatostatin Receptor Subtypes in the Rat Pituitary
Authors: Lam Karen S.L. , Wong Rachel L.C. 
Published: April 2003

Circulating TSH levels are increased in hypothyroidism and suppressed in hyperthyroidism. On the other hand, the hypothalamic hormone somatostatin suppresses basal and TRH-induced TSH release, an effect which is enhanced by thyroid hormones. To investigate whether the effects of thyroid hormones on TSH secretion may be mediated in part through alterations in the gene expression of pituitary somatostatin receptors (SSTR), 3-week-old male Sprague-Dawley rats were rendered hypothyroid with antithyroid drugs for 3 weeks. Total RNA extracted from anterior pituitaries were analysed for SSTR mRNA levels, using Northern blot hybridization. Compared to controls, hypothyroid rats had significantly lower pituitary mRNA levels of SSTR1 and SSTR2 (p < 0.0001 for both, n = 16); the reductions could be prevented by T<sub>4</sub> supplementation (3 µg/100 g body weight/day i.p.). In vitro studies using GH<sub>4</sub>C<sub>1</sub> rat pituitary cells showed that the addition of T<sub>3</sub> 10<sup>–8</sup> <i>M</i> to cells cultured in charcoal-stripped bovine calf serum resulted in significant increases in mRNA levels of SSTR1 (p < 0.0001; n = 7) and the two transcripts of SSTR2 (p < 0.0005; n = 7). The increase for SSTR1 showed no further increase with higher doses of T<sub>3</sub>, but was time-dependent and could be seen consistently after 8 h of incubation. We conclude that thyroid hormones regulate the gene expression of SSTR subtypes in the pituitary, via a direct action on anterior pituitary cells. Changes in SSTR gene expression may contribute to the increase in circulating TSH levels in hypothyroidism.