bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid Maintains Pulsatile Secretion of Luteinizing Hormone under Infectious Stress Condition
Authors: Matsuwaki Takashi , Watanabe Erina , Suzuki Masatoshi , Yamanouchi Keitaro , Nishihara Masugi 
Published: April 2003

Abstract
We have previously shown that TNF-α, a major proinflammatory cytokine, suppressed hypothalamic GnRH pulse generator activity and that this inhibitory effect was enhanced by α-helical CRH, a CRH receptor antagonist. The present study was conducted to elucidate the involvement of glucocorticoid (GC) in modulating LH pulses under infectious stress condition. Adrenalectomy (ADX) markedly enhanced the suppressive effect of TNF-α (1 μg), injected iv, on LH pulses in ovariectomized (OVX) rats. Pretreatment with a sc injection of corticosterone (10 mg) almost completely restored LH pulses after TNF-α injection in OVX/ADX animals. Injection of TNF-α increased the number of c-Fos-immunoreactive cells in the supraoptic nucleus (SON), the dorsomedial hypothalamic nucleus (DMH), and the parvocellular region of the paraventricular nucleus (PVN), which was more prominent in OVX/ADX than OVX animals except in the DMH. Pretreatment with corticosterone decreased the number of Fos-immunoreactive cells in the PVN and SON but not in the DMH. These results suggest that GC has a potent protective effect on LH pulsatility under conditions of infectious stress, the mechanism of which involves at least the suppression of the excitability of PVN and SON neurons. In addition, the DMH does not seem to mediate the central action of GC, though it may play an important role in inducing pathophysiological reactions to invasive stress.
Pregnancy Enhances the Angiotensin (Ang)-(1–7) Vasodilator Response in Mesenteric Arteries and Increases the Renal Concentration and Urinary Excretion of Ang-(1–7)
Authors: Neves Liomar A. A. , Williams Aleck F. , Averill David B. , Ferrario Carlos M. , Walkup Michael P. , Brosnihan K. Bridget 
Published: April 2003

Abstract
The vasoactive effect of angiotensin (Ang)-(1–7) in mesenteric resistance arteries together with its plasma and kidney concentration and urinary excretion was assessed in pregnant and virgin rats. Mesenteric arteries (230–290 μm) were mounted in a pressurized myograph system and Ang-(1–7) concentration-dependent response curves (10−10–10−5m) were determined in arteries preconstricted with endothelin-1 (10−7m). The Ang-(1–7) response was investigated in vessels with and without pretreatment with the Ang-(1–7) antagonist [d-[Ala7]-Ang-(1–7)] (10−7m). Ang-(1–7) caused a significantly enhanced, concentration-dependent dilation of mesenteric vessels (EC50 = 2.7 nm) from pregnant compared with virgin female rats. d-[Ala7]-Ang-(1–7) eliminated the vasodilator effect of Ang-(1–7). There was no significant change in plasma concentration of Ang-(1–7) in pregnant animals. On the other hand, 24 h urinary excretion and kidney concentration of Ang-(1–7) were significantly higher in pregnant animals. The increased mesenteric dilation to Ang-(1–7) with enhanced kidney concentration and 24 h urinary excretion rate of Ang-(1–7) suggests an important role for this peptide in cardiovascular regulation during pregnancy.
The Soy Isoflavone Genistein Decreases Adipose Deposition in Mice
Authors: Naaz Afia , Yellayi Srikanth , Zakroczymski Melissa A. , Bunick David , Doerge Daniel R. , Lubahn Dennis B. , Helferich William G. , Cooke Paul S. 
Published: April 2003

Abstract
Adipose tissue is responsive to estrogen and expresses both estrogen receptor α and β. To test the hypothesis that the estrogenic soy isoflavone genistein can have effects on adipose tissue, juvenile or adult C57/BL6 mice were ovariectomized and given daily injections of vehicle, 17β-estradiol (5 μg/kg·d) or genistein (8–200 mg/kg·d) sc for 21–28 d. To test effects of dietary genistein, 25- to 27-d-old mice were fed diets containing 0–1500 parts per million (ppm) genistein for 12 d. Mice were killed and fat pads weighed. Parametrial fat pads were used for morphometric and Northern analysis. Genistein injections decreased adipose weight and adipocyte circumference at higher doses; effects in adult and juvenile mice were similar. Genistein decreased lipoprotein lipase mRNA, which may be a critical aspect of its adipose effects. Juveniles fed 500-1500 ppm dietary genistein had dose-responsive decreases in fat pad weights of 37–57%, compared with controls; 300 ppm genistein did not cause decreases. Genistein doses of 300, 500, 1000, and 1500 ppm produced serum genistein concentrations of 1.02 ± 0.14 μm, 1.79 ± 0.32 μm, 2.55 ± 0.18 μm, and 3.81 ± 0.39 μm, respectively. These results indicate dietary genistein at 500-1500 ppm produces antilipogenic effects in mice at serum levels that humans are realistically exposed to.
Ovine Placental Lactogen-Induced Heterodimerization of Ovine Growth Hormone and Prolactin Receptors in Living Cells Is Demonstrated by Fluorescence Resonance Energy Transfer Microscopy and Leads to Prolonged Phosphorylation of Signal Transducer and Activator of Transcription (STAT)1 and STAT3
Authors: Biener Eva , Martin Cyril , Daniel Nathalie , Frank Stuart J. , Centonze Victoria E. , Herman Brian , Djiane Jean , Gertler Arieh 
Published: April 2003

AbstractHEK-293T cells transiently transfected with ovine (o) GH receptor (GHR) and prolactin receptor (PRLR) constructs respectively tagged downstream with cyan or yellow fluorescent proteins were used to study ovine placental lactogen (oPL)-stimulated heterodimerization by fluorescence resonance energy transfer (FRET) microscopy. The oPL-stimulated transient heterodimerization of GHR and PRLR had a peak occurring 2.5–3 min after oPL application, whereas oGH or oPRL had no effect at all. The results indicate none or only little dimerization occurring before the hormonal stimulation. The effect of heterodimerization was studied by comparing activation of Janus kinase 2, signal transducer and activator of transcription (STAT)1, STAT3, STAT5, and MAPK in Chinese hamster ovary cells stably transfected with chimeric genes encoding receptors consisting of cytosolic and transmembrane parts of oGHR and oPRLR, extracellular domains of human granulocyte and macrophage colony-stimulating factor (hGM-CSF) receptor α or β, and cells transfected with the two forms (α or β) of PRLR and GHR. Functionality of those proteins was verified by hGM-CSF-induced phosphorylation of both intracellular PRLR and GHR domains and hGM-CSF-induced heterodimerization was documented by chimeric receptor coimmunoprecipitation. Homodimerization or heterodimerization of PRLRs and GHRs had no differential effect on activation of STAT5 and MAPK. However, heterodimerization resulted in a prolonged phosphorylation of STAT1 and in particular STAT3, suggesting that the heterodimerization of α-oGHR and β-oPRLR is able to transduce a signal, which is distinct from that occurring on homodimeric associations.
Regulation of Aldosterone Synthase Gene Expression in the Rat Adrenal Gland and Central Nervous System by Sodium and Angiotensin II
Authors: Ye Ping , Kenyon Christopher J. , MacKenzie Scott M. , Seckl Jonathan R. , Fraser Robert , Connell John M. C. , Davies Eleanor 
Published: April 2003

AbstractWe have developed a highly sensitive QRT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs to study their expression in the rat brain in response to dietary sodium manipulation and angiotensin (Ang)II infusion. Male Wistar Kyoto rats (n = 6) were fed normal, high, or low sodium diets for 12 d or were administered AngII or vehicle for 7 d. CYP11B2 and CYP11B1 expression was measured in RNA from adrenal gland and discrete brain regions using real-time QRT-PCR. Sodium restriction increased adrenal CYP11B2 expression 57-fold from 1.0 × 105 ± 0.6 × 105 to 57 × 105 ± 22 × 105 copies/μg RNA (mean ± sem; P &lt; 0.05);in the hippocampus, 14-fold from 5.4 × 102 ± 0.8 × 102 to 74 × 102 ± 31 × 102 copies/μg RNA (P &lt; 0.05); and in the cerebellum, 5-fold from 1.9 × 103 ± 0.7 × 103 to 9.9 × 103 ± 3.0 × 103 copies/μg RNA (P &lt; 0.01). CYP11B2 gene expression in the brainstem and hypothalamus was not affected. High-sodium diet reduced adrenal CYP11B2 expression to 0.19 × 105 ± 0.1 × 105 copies/μg RNA (P &lt; 0.05) but did not affect central nervous system (CNS) expression significantly. AngII significantly increased adrenal CYP11B2 expression but did not affect CNS expression. Brain CYP11B1 mRNA levels were 10- to 1000-fold higher than CYP11B2 but were unaffected by dietary sodium or AngII. To summarize, we have identified a local CYP11B2 response to sodium depletion in the hippocampus and cerebellum. This is the first such regulation of CYP11B2 transcription to be identified in the CNS.
PERK eIF2α Kinase Regulates Neonatal Growth by Controlling the Expression of Circulating Insulin-Like Growth Factor-I Derived from the Liver
Authors: Li Yulin , Iida Kaori , O’Neil Jeff , Zhang Peichuan , Li Sheng’ai , Frank Ami , Gabai Aryn , Zambito Frank , Liang Shun-Hsin , Rosen Clifford J. , Cavener Douglas R. 
Published: April 2003

AbstractHumans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2α kinase) show severe postnatal growth retardation. In mice, growth retardation in Perk−/− mutants is manifested within the first few days of neonatal development. Growth parameters of Perk−/− mice, including comparison of body weight to length and organ weights, are consistent with proportional dwarfism. Tibia growth plates exhibited a reduction in proliferative and hypertrophic chondrocytes underlying the longitudinal growth retardation. Neonatal Perk−/− deficient mice show a 75% reduction in liver IGF-I mRNA and serum IGF-I within the first week, whereas the expression of IGF-I mRNA in most other tissues is normal. Injections of IGF-I partially reversed the growth retardation of the Perk−/− mice, whereas GH had no effect. Transgenic rescue of PERK activity in the insulin- secreting β-cells of the Perk−/− mice reversed the juvenile but not the neonatal growth retardation. We provide evidence that circulating IGF-I is derived from neonatal liver but is independent of GH at this stage. We propose that PERK is required to regulate the expression of IGF-I in the liver during the neonatal period, when IGF-I expression is GH-independent, and that the lack of this regulation results in severe neonatal growth retardation.
Adenovirus-Mediated Expression of Human Prorelaxin Promotes the Invasive Potential of Canine Mammary Cancer Cells
Authors: Silvertown Josh D. , Geddes Brad J. , Summerlee Alastair J. S. 
Published: April 2003

AbstractThis study reports the characterization of a recombinant adenoviral vector containing a tetracycline-regulatable promoter, driving the bicistronic expression of the human H2 preprorelaxin (hH2) cDNA and enhanced green fluorescent protein, via an internal ribosomal entry site. An hH2 ELISA was used to measure the secreted levels of recombinant hH2 in transfected canine (CF33.Mt) and human (MDA-MB-435) mammary cancer cell lines over a 6-d period; secreted peptide peaked on d 2 and 4 for the canine and human cell types, respectively. An unprocessed hH2 immunoreactive form of approximately 18 kDa was identified by Western blotting analysis and confirmed by mass spectrometry, suggesting that prorelaxin remains unprocessed in these cell types. The biological activity of the adenovirally expressed human prorelaxin was measured in the established human monocytic cell line THP-1 cAMP ELISA and in an in vitro Transwell cell migration system. Exogenous recombinant hH2 and adenovirally-mediated delivery of prorelaxin to CF33.Mt cells conferred a significant migratory action in the cells, compared with controls. Cell proliferation assays were performed to discount the possibility that the effect of relaxin was mitogenic. Thus, we have demonstrated that prorelaxin has the ability to facilitate cell migration processes exclusive of its ability to stimulate cell proliferation. In validating this adenovirus-based system, we have created a potential tool for further exploration of the physiology of relaxin in mammalian systems.
A Minimal Algorithm for the Bounded Knapsack Problem
Authors: Pisinger David 
Published: April 2003

The Bounded Knapsack Problem (BKP) is a generalization of the 0-1 Knapsack Problem where a bounded amount of each item type is available. Currently, the most efficient algorithm for BKP transforms the data instance to an equivalent 0-1 Knapsack Problem, which is solved efficiently through a specialized algorithm. However, this paper demonstrates that the transformation introduces many similarly weighted items, resulting in very hard instances of the 0-1 Knapsack Problem. To avoid these problems, we propose a specialized algorithm that solves an expanding core problem through dynamic programming such that the number of enumerated item types is minimal. Sorting and reduction is done by need, resulting in very little effort for the preprocessing. Compared to other algorithms for BKP, the presented algorithm uses tighter reductions and enumerates considerably less item types. Computational experiments are presented, showing that the presented algorithm outperforms all previously published algorithms for BKP.
Gabapentin and Posttraumatic Stress Disorder
Authors: Malek-Ahmadi Parviz 
Published: April 2003

OBJECTIVE: To report the effects of gabapentin in a patient with concurrent depression and posttraumatic stress disorder (PTSD) and review the use of antiepileptic drugs (AEDs) in PTSD. CASE SUMMARY: A 37-year-old Latin American woman was being treated for major depression and PTSD. While the depressive symptoms were in remission, she reported a significant reduction in the frequency of her flashbacks after gabapentin was added to venlafaxine. She did not receive any type of psychotherapy. The flashbacks recurred after she discontinued gabapentin. DISCUSSION: While the improvement reported by the patient may have been related to a placebo effect or spontaneous recovery, treatment with gabapentin may have played a role in alleviating the flashbacks. Other published reports suggest that AEDs have a beneficial effect on some PTSD symptoms. CONCLUSIONS: AEDs may be of some therapeutic value in patients with PTSD. Future controlled studies are warranted to investigate the effectiveness of these agents.
Topiramate Titration to Response: Analysis of Individualized Therapy Study (TRAITS)
Authors: Dodson W Edwin , Kamin Marc , Kraut Lesley , Olson William H , Wu Shu-Chen 
Published: April 2003

OBJECTIVE: To evaluate the relationship between baseline seizure frequency and stabilized topiramate dosage and the effect of individualized treatment on tolerability in adults with partial-onset seizures receiving other antiepileptic drugs (AEDs). METHODS: In this 20-week, open-label trial, dosages of medications were adjusted according to clinical response. Dosage and seizure response data were analyzed for 2 groups defined by baseline seizure frequency: <4 and ≥4 seizures per month. RESULTS: In the outcome evaluable population (n = 471), the mean ± SEM stable topiramate dosage was 303 ± 139 mg/d when baseline seizure frequency was <4 seizures/month and 341 ± 153 mg/d when baseline seizure frequency was ≥4 seizures/month (p = 0.005). The most common adverse events were somnolence (8.5%), fatigue (7.3%), nausea (5.3%), and dizziness (5.0%). Cognitive complaints were reported by <3% of patients. When concomitant AED dosages were reduced, 14% of patients discontinued topiramate due to adverse events compared with 23% if the concomitant AED dosage was unchanged or increased. CONCLUSIONS: When clinicians individualize topiramate dosage according to clinical response, the stabilized topiramate dosage as add-on therapy is influenced by baseline seizure frequency. Topiramate tolerability is improved when dosages of concomitant AEDs are reduced.
An Interventional Program to Improve Antibiotic Use
Authors: Feucht Cynthia L , Rice Louis B 
Published: April 2003

BACKGROUND: Large volume and often inappropriate use of specific antimicrobial agents increase selective pressure for emergence of resistant bacteria and place strain on the pharmacy budget. OBJECTIVE: To initiate a multidisciplinary program designed to align intravenous vancomycin and fluoroquinolone prescribing practices with guidelines for appropriate use of these agents. METHODS: A multidisciplinary, prospective interventional program was implemented to encourage early discontinuation of inappropriate vancomycin and fluoroquinolone therapy and decrease inappropriate duplicative gram-negative coverage using fluoroquinolones. A computerized review was performed for patients receiving intravenous vancomycin and fluoroquinolones for 1998 in a Veterans Affairs Medical Center. In June 1999, guidelines were disseminated and an interventional program was initiated, with a monthly conference for medical residents regarding antimicrobial resistance and local hospital practices. Concurrently, a prospective review of new orders was assessed by the clinical pharmacist and interventions performed when inappropriate use occurred. RESULTS: The interventional program was successful in reducing unnecessary duplicative gram-negative coverage with intravenous fluoroquinolones by 26% (p < 0.001) from 1998 to 2001. Overall, a 43% reduction in the number of courses of intravenous fluoroquinolones was seen during these 4 years. Courses lasting >5 days were reduced by 22% (p < 0.001). Vancomycin prescriptions deemed inappropriate that were administered >5 days were reduced by 16% (p < 0.001) during the same time period. The interventions performed by the clinical pharmacist were deemed successful, with a 76% acceptance rate by providers. CONCLUSIONS: Education of physicians through monthly conferences and personal interventions resulted in an increase in appropriate empiric antibiotic use, a decrease in the duration of inappropriate use, and a decrease in duplicate gram-negative coverage.
Excessive Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia
Authors: Reichert Marc G , MacGregorew A , Kincaid Edward H , Dolinski Sylvia Y 
Published: April 2003

OBJECTIVE: To report 4 patients who became excessively anticoagulated with the recommended or lower starting doses of argatroban during treatment for heparin-induced thrombocytopenia type II (HIT-II) in a cardiothoracic intensive care unit. CASE SUMMARY: Four patients were treated with argatroban after confirmation of HIT-II after cardiac surgery. In 3 patients, argatroban was initiated at the recommended starting dose of 2 μg/kg/min; in 1 patient, therapy was initiated at 1 μg/kg/min. All patients had relatively normal hepatic function. In all cases, the resulting activated partial thromboplastin time was supertherapeutic and exceeded 100 seconds in 3 patients. Additionally, argatroban clearance appeared to be prolonged upon discontinuation. DISCUSSION: Argatroban pharmacokinetics in critically ill patients have not been investigated. Our case series demonstrates the potential over-anticoagulation that can occur in this patient population despite relatively normal hepatic function. An objective causality assessment revealed that the adverse drug event in these patients was probably caused by administration of argatroban. CONCLUSIONS: Formal pharmacokinetic studies of argatroban are needed in critically ill patients in order to optimize therapy.
Acute Tumor Lysis Syndrome Secondary to Hydroxyurea in Acute Myeloid Leukemia
Authors: Seki Jack T , Al-Omar Hamad M , Amato Dominick , Sutton David MC 
Published: April 2003

OBJECTIVE: To report 2 cases of acute tumor lysis syndrome (ATLS) associated with hydroxyurea treatment. CASE SUMMARY: A 79-year-old woman diagnosed with chronic lymphocytic leukemia presented with an acute blastic transformation. She was promptly hydrated, started on allopurinol, and treated with hydroxyurea. About 24 hours later, her biochemistry panel showed parameters consistent with ATLS when compared with pretreatment levels. The second case was a 76-year-old man newly diagnosed with acute myeloid leukemia presenting with high blast fraction. He was given appropriate hydration and allopurinol prophylaxis, and was started on high-dose hydroxyurea treatment. He became symptomatic after 12 hours and results of his blood work were consistent with ATLS. DISCUSSION: ATLS is a well-known metabolic disturbance that occurs after cell destruction of rapidly growing tumors. In standard doses, hydroxyurea leads to cell death in the S phase and is not thought to cause significant cell lysis. However, in large doses, it possibly acts by a different mechanism and had a direct cytolytic effect associated with ATLS in our patients. CONCLUSIONS: Although ATLS caused by hydroxyurea appears to be rare, patients at risk should be closely monitored for this complication. An objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction was probable between ATLS and hydroxyurea therapy in these 2 patients.
Comparing Therapies for Postmenopausal Osteoporosis Prevention and Treatment
Authors: Eichner Samantha F , Lloyd Kimberly B , Timpe Erin M 
Published: April 2003

OBJECTIVE: To review the literature concerning the efficacy of calcium, hormone replacement therapy (HRT), bisphosphonates, selective estrogen receptor modulators, and calcitonin in the prevention and treatment of postmenopausal osteoporosis. DATA SOURCES: Articles were identified through searches of the MEDLINE (1966–July 2002), EMBASE (1980–July 2002), and International Pharmaceutical Abstracts (1970–July 2002) databases using the key words osteoporosis, postmenopausal, fracture, calcium, vitamin D, hormone replacement therapy, bisphosphonates, alendronate, risedronate, raloxifene, and calcitonin. Additional references were located through review of the bibliographies of the articles cited. Searches were not limited by time restriction, language, or human subject. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational studies of the use of calcium and antiresorptive therapies for the prevention and treatment of postmenopausal osteoporosis were selected. Articles evaluating bone mineral density (BMD) or fracture efficacy were included in this review. DATA SYNTHESIS: HRT, bisphosphonates, raloxifene, and calcitonin have demonstrated stabilization of and improvement in BMD. Randomized clinical trials have shown fracture risk reduction with bisphosphonates, raloxifene, HRT, calcium, and calcitonin. The largest risk reductions have been reported with use of bisphosphonates in several trials. CONCLUSIONS: Several therapeutic options with well-documented improvements in BMD and reductions in fracture risk are available to women for the prevention and treatment of postmenopausal osteoporosis.