bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a glucose–insulin–potassium infusion algorithm in hospitalized diabetic patients
Authors: Bonnier M. , Lönnroth P. , Gudbjörnsdottir S. , Attvall S. , Jansson P.‐A. 
Published: March 2003

Abstract.  Bonnier M, Lönnroth P, Gudbjörnsdottir S, Attvall S, Jansson P‐A (Sahlgrenska University Hospital, Gothenburg, Sweden). Validation of a glucose–insulin–potassium infusion algorithm in hospitalized diabetic patients. J Intern Med 2003; 253: 189–193.Background.  The short and long time prognoses of acute internal medicine diseases in diabetic patients are dependent on the level of diabetes control.Objectives.  Validation of a novel glucose–insulin–potassium (GIK) infusion algorithm to optimize metabolic control in hospitalized diabetic patients.Subjects.  We randomized 33 diabetic patients admitted to Sahlgrenska University Hospital with acute internal medicine diseases to either GIK infusion or multiple injection therapy (MIT). The GIK infusion rate and the MIT were controlled according to special algorithms. The treatment efficacy was evaluated through comparisons of capillary blood glucose eight times on day 2 of the study.Results.  The GIK infusion led to significantly lower mean blood glucose when compared with MIT [10.1 (9.0–11.2) vs. 12.3 (9.3–14.4) mmol L−1, median and interquartile range, P < 0.01]. Four episodes of hypoglycaemia without loss of consciousness were recorded in the GIK group whereas no hypoglycaemic event occurred in the MIT group. A mean of 1 (1–3) episodes of blood glucose levels above 12.0 mmol L−1 were recorded in the GIK group compared with 3.5 (1.5–5.0) in the MIT group, P < 0.01.Conclusions.  The algorithm used for the GIK infusion gave an acceptable level of metabolic control and this insulin infusion protocol is safe enough to be used by the nursing staff on a general internal medicine ward.
Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT)
Authors: Felmeden D. C. , Spencer C. G. C. , Blann A. D. , Beevers D. G. , Lip G. Y. H. 
Published: March 2003

Abstract.  Felmeden DC, Spencer CGC, Blann AD, Beevers DG, Lip GYH (University Department of Medicine, City Hospital, Birmingham, UK). Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT). J Intern Med 2003; 253: 81–91.Background.  Hypertension is an important risk factor for cardiovascular disease. The latest guidelines recommend regular physical exercise as initial step or adjunct in the treatment of hypertension. We investigated the association between physical activity and the degree of hypertension, as well as the relation to indices of endothelial damage/dysfunction and angiogenesis.Methods.  We studied 234 patients with hypertension (198 males; mean age 64 years; mean blood pressure 166/90 mmHg), who were compared with 60 age and sex‐matched healthy normotensive controls. We assessed the patient's physical activity using the validated Baecke physical activity questionnaire and measured flow‐mediated dilatation (FMD) of the brachial artery and von Willebrand factor (vWf) as indices of endothelial damage/dysfunction, whilst angiogenesis was assessed by measurement of plasma vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt‐1) both by ELISA.Results.  When hypertensive patients were compared with the controls, there was no statistically significant difference in total physical activity score using the Baecke questionnaire although plasma VEGF and vWf levels were higher, but sFlt‐1 levels and FMD lower (all P < 0.001). Patients with high physical activity were younger, and had lower mean diastolic blood pressure and 10‐year Framingham stroke risk, when compared with those with low physical activity; but indices of endothelial damage/dysfunction and angiogenesis were not significantly different.Conclusion.  Physical activity scores in hypertensive patients are not significantly different from healthy normotensive controls, and there appears to be no relation to the abnormal processes of endothelial damage/dysfunction and angiogenesis seen in hypertensives.
Overview of the clinical efficacy of investigational anticancer drugs
Authors: Nygren P. , Larsson R. 
Published: March 2003

Abstract.Nygren P, Larsson R (Section of Oncology and Section of Clinical Pharmacology, University Hospital, Uppsala, Sweden). Overview of the clinical efficacy of investigational anticancer drugs (Review). J Intern Med 2003; 253: 46–75.The purpose of this overview was to make a broad inventory of investigational drugs for medicinal cancer treatment and, specifically, to indicate the evidence of clinical efficacy. Information was retrieved from electronic database searches in Medline and CANCERLIT and relevant published reviews. As the most recent findings are first reported as conference abstracts, an important basis for identification of new drugs and clinical results was a hand search of 13 392 abstracts from five major recent cancer conferences. A total of 209 investigational approaches or drugs were identified and classified into one of eight groups according to proposed mechanism of action. For 28 drugs/approaches survival data were available from randomized controlled trials. Statistically significant benefit was observed for only 12. In earlier phases no or modest anticancer activity was reported. It is speculated that the expanding knowledge in tumour biology might not easily translate into new substantially better anticancer drugs.
Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon economy and lifetime resolution
Authors: Gerritsen H. C. , Asselbergs M. A. H. , Agronskaia A. V. , Van Sark W. G. J. H. M. 
Published: March 2003

SummaryIn this paper a detailed discussion is presented of the factors that affect the fluorescence lifetime imaging performance of a scanning microscope equipped with a single photon counting based, two‐ to eight‐channel, time‐gated detection system. In particular we discuss the sensitivity, lifetime resolution, acquisition speed, and the shortest lifetimes that can be measured. Detection systems equipped with four to eight time‐gates are significantly more sensitive than the two time‐gate system. Only minor sensitivity differences were found between systems with four or more time‐gates. Experiments confirm that the lifetime resolution is dominated by photon statistics. The time response of the detector determines the shortest lifetimes that can be resolved; about 25 ps for fast MCP‐PMTs and 300–400 ps for other detectors. The maximum count rate of fast MCP‐PMTs, however, is 10–100 times lower than that of fast PMTs. Therefore, the acquisition speed with MCP‐PMT based systems is limited. With a fast PMT operated close to its maximum count rate we were able to record a fluorescence lifetime image of a beating myocyte in less than one second.
Freeze‐dried and resin‐embedded biological material is well suited for ultrastructure research
Authors: Edelmann L. 
Published: March 2003

SummaryTransmission electron micrographs of different biological material, cryofixed, freeze‐dried and embedded in Spurr's resin, in Epon, or in Lowicryl, are presented. The structure preservation obtained either without or with application of chemical fixatives after drying showed that freeze‐dried embedded specimens are particularly well suited for new morphological, immunocytochemical and microanalytical studies aimed at detecting the life‐like subcellular distribution of mobile macromolecules and ions. The results also indicate that the removal of cell water by freeze‐drying from the areas of best cryofixation is relatively slow. Ultrathin sections of well cryofixed biological material embedded after freeze‐drying in Spurr's resin or Epon reveal cellular plasma phases with very fine granularities and well defined membranes in negative contrast. This may be due to the preservation of the original structure of cellular macromolecules with a considerable amount of their hydration water. Sublimation studies with differently hydrated and cryofixed macromolecules are suggested to settle this issue.
Optic fibre bundle contact imaging probe employing a laser scanning confocal microscope
Authors: Dubaj V. , Mazzolini A. , Wood A. , Harris M. 
Published: March 2003

SummaryA small diameter (600 µm) fused optic fibre imaging bundle was used as a probe to compare fluorescent specimens by direct contact imaging using both a conventional fluorescence microscope and a laser scanning confocal microscope (LSCM) system. Green fluorescent polyester fibres placed on a green fluorescent cardboard background were used to model biological tissue. Axial displacement curves support the hypothesis that pinhole size in the LSCM system reduces the contribution of non‐focal plane light. Qualitative comparison showed that the LSCM system produced superior image quality and contrast over the conventional system. The results indicate that the new LSCM–probe combination is an improvement over conventional fluorescence–probe systems. This study shows the feasibility of employing such a small diameter probe in the investigation of biological function in difficult to access areas.
Transmitted light microscopy of a fibre reinforced metal
Authors: Moser B. , Rossoll A. , Weber L. , Beffort O. , Mortensen A. 
Published: March 2003

SummaryA method is presented for studying fibre damage in continuous fibre reinforced composites. It is based on contrasting the transmission of light through intact translucent fibres with the light through fractured or dead‐ended fibres. The method is applied in order to detect processing‐induced fibre fractures in aluminium reinforced with continuous alumina fibres.
Basic Fibroblast Growth Factor Priming Increases the Responsiveness of Immortalized Hypothalamic Luteinizing Hormone Releasing Hormone Neurones to Neurotrophic Factors
Authors: Gallo F. , Morale M. C. , Tirolo C. , Testa N. , Farinella Z. , Avola R. , Beaudet A. , Marchetti B. 
Published: March 2003

AbstractThe participation of growth factors (GFs) in the regulation of luteinizing hormone releasing hormone (LHRH) neuronal function has recently been proposed, but little is known about the role played by GFs during early LHRH neurone differentiation. In the present study, we have used combined biochemical and morphological approaches to study the ability of a number of GFs normally expressed during brain development, including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin and insulin‐like growth factor I (IGF‐I) to induce survival, differentiation, proliferation, and phenotypic expression of immortalized (GT1‐1) LHRH neurones in vitro, at early (3‐days in vitro, 3‐DIV) and late (8‐DIV) stages of neuronal differentiation. Comparison of GF‐treated vs untreated neurones grown in serum‐deprived (SD) medium demonstrated bFGF to be the most potent, and insulin the least active in promoting neuronal differentiation. Thus, at both 3‐DIV and 8‐DIV, but especially at 8‐DIV, bFGF induced the greatest increase in the total length and number of LHRH processes/cell and in growth cone surface area. bFGF was also the most active at 3‐DIV, and IGF‐I at 8‐DIV, in counteracting SD‐induced cell death, whereas EGF was the most potent in increasing [3H]thymidine incorporation. All GFs studied decreased the spontaneous release of LHRH from GT1‐1 cells when applied at 3‐DIV or 8‐DIV, except for insulin which was inactive at both time‐points and bFGF which was inactive at 8‐DIV. Pre‐treatment of GT1‐1 cells with a suboptimal (‘priming’) dose of bFGF for 12 h followed by application of the different GFs induced a sharp potentiation of the neurotrophic and proliferative effects of the latter and particularly of those of IGF‐I. Moreover, bFGF priming counteracted EGF‐induced decrease in LHRH release and significantly stimulated LHRH secretion following IGF‐I or insulin application, suggesting that bFGF may sensitize LHRH neurones to differentiating effects of specific GFs during development.
Corticotropin‐Releasing Hormone and Arginine Vasopressin: mRNA and Secretion are Differentially Regulated According to the Pattern of Exposure to Noradrenaline in Rat Hypothalamic Neurones
Authors: Haisenleder D. J. 
Published: March 2003

AbstractHypothalamic corticotropin‐releasing hormone (CRH) and arginine vasopressin (AVP) are secreted from the median eminence in a pulsatile manner and regulated by noradrenaline during stress. This study investigated the effect of pulsatile noraderanaline on CRH/AVP mRNAs and secretion. Foetal hypothalamic neurones were cultured on plastic coverslips, inserted into perifusion chambers and noraderanaline pulses given at various doses or pulse intervals for 24 h. CRH and AVP release rose in a dose dependant manner; however, maximal increases in mRNAs were seen with an intermediate noraderanaline pulse dose. The effect of noraderanaline pulse frequency was determined by giving noraderanaline pulses at intervals of 15–120 min vs continuous noraderanaline. Both pulsatile and continuous noraderanaline increased CRH and AVP release, but secretion was reduced after 22 h of treatment in the continuous noraderanaline and rapid pulse groups. CRH mRNA levels were maximally increased by medium interval pulses and AVP mRNA by rapid interval pulses. Neither CRH nor AVP mRNAs were stimulated by continuous noraderanaline. To determine noraderanaline specificity, pulses of veratridine (VER; 15–120 min intervals) vs continuous VER were examined. Only pulsatile VER increased CRH and AVP mRNAs, with maximal effects seen with the 60 min pulse interval for both. Thus, noraderanaline pulse pattern regulates CRH and AVP gene expression in both a coordinate and differential manner. Since noraderanaline plays an important role during stress, the pattern of noraderanaline signals may be critical to the observed changes in CRH and AVP expression.
Maternal Undernutrition in Early Gestation Alters Molecular Regulation of the Hypothalamic‐Pituitary‐Adrenal Axis in the Ovine Fetus
Authors: Hawkins P. , Hanson M. A. , Matthews S. G. 
Published: March 2003

AbstractWe have demonstrated previously that plasma adrenocorticotropin hormone and cortisol responses to exogenous and endogenous stimuli are reduced in fetuses of mildly undernourished ewes. In the present study, we examined the molecular regulation of fetal hypothalamic‐pituitary‐adrenal (HPA) axis function at 127–130 days gestation (dGA) following 15% reduction in maternal nutrition between 0 and 70 dGA. Usingin situhybridization, we found that corticotropin releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) was lower in fetuses from nutrient restricted ewes than in controls. Restricted fetuses also had greater levels of mRNA encoding preproenkephalin (PENK) and magnocellular arginine vasopressin (AVP) in the PVN. Expression of oxytocin mRNA and parvocellular AVP mRNA in the PVN and pro‐opiomelanocortin mRNA in the pituitary were unchanged. Glucocorticoid receptor mRNA expression was unaltered at the PVN, but was reduced (> 40%) in the anterior pituitary of restricted fetuses. Northern blot analysis demonstrated that levels of adrenal P450sccmRNA and P450C17mRNA were not different between the groups. We conclude that the reduction in HPA function reported previously is mediated, at least in part, by a decrease in expression of CRH mRNA and increase in PENK mRNA in the PVN.
Age‐Related Changes in Hypothalamic Gonadotropin‐Releasing Hormone and N‐Methyl‐d‐Aspartate Receptor Gene Expression, and their Regulation by Oestrogen, in the Female Rat
Authors: Gore A. C. , Oung T. , Woller M. J. 
Published: March 2003

AbstractDuring reproductive ageing, the oestrous cycles of female rats become irregular and eventually cease. The mechanisms for reproductive senescence in rodents are believed to involve changes in hypothalamic neurones, including gonadotropin‐releasing hormone (GnRH) cells and their afferent inputs. In addition, effects of oestrogen on hypothalamic function may vary in animals of different ages. These issues were addressed using young (aged 4–5 months), middle‐aged (12–14 months) and old (24–26 months) female Sprague‐Dawley rats. Animals were ovariectomized and given oestrogen or vehicle replacement. They were killed and the preoptic area‐anterior hypothalamus (POA‐AH) and the medial basal hypothalamus‐median eminence (MBH‐ME) were dissected out, RNA extracted, and RNase protection assay used to quantify gene expression of several hypothalamic molecules. In the first experiment, GnRH RNA levels were measured in the POA‐AH. No effects of ageing or oestrogen were observed on GnRH gene expression. This finding suggests that ageing and oestrogen may affect GnRH release from neuroterminals independently of de novo biosynthesis, and that this may involve other neurones that affect GnRH neurosecretory function. In the second experiment, we investigated changes in N‐methyl‐d‐aspartate (NMDA) receptor subunit mRNA levels. These receptors play an important regulatory role in mediating effects of glutamate on GnRH function, and are themselves regulated by oestrogen and ageing. NMDA receptor subunit (NR) 1, 2a and 2b mRNA levels were quantified in the POA‐AH and MBH‐ME, the sites of GnRH perikarya and neuroterminals, respectively. In general, oestrogen had inhibitory effects on NR1 and NR2a, and differential effects on NR2b subunit mRNA levels. NMDA receptor subunit mRNA levels also changed during ageing: age‐related decreases in NR1 mRNA occurred in the MBH‐ME, and an age‐related increase in NR2b mRNA occurred in the POA‐AH. Taken together, these results demonstrate subunit‐ and region‐specific changes in hypothalamic NMDA receptor subunit gene expression with oestrogen and ageing. These alterations could have implications for the physiological effects of glutamate on its NMDA receptor, and impact the regulation of reproductive and other neuroendocrine and autonomic functions by hypothalamic glutamatergic inputs.
Metyrapone‐Induced Glucocorticoid Depletion Modulates Tyrosine Hydroxylase and Phenylethanolamine N‐Methyltransferase Gene Expression in the Rat Adrenal Gland by a Noncholinergic Transsynaptic Activation
Authors: Laborie C. , Van Camp G. , Bernet F. , Montel V. , Dupouy J. P. 
Published: March 2003

AbstractThe hypothalamic corticotropin‐releasing hormone system and the sympathetic nervous system are anatomically and functionally interconnected and hormones of the hypothalamic‐pituitary‐adrenocortical axis contribute to the regulation of catecholaminergic systems. To investigate the role of glucocorticoids on activity of the adrenal gland, we analysed plasma and adrenal catecholamines, tyrosine hydroxylase (TH) and phenylethanolamine N‐methyltransferase (PNMT) mRNA expression in rats injected with metyrapone or dexamethasone. Metyrapone‐treated rats had significantly lower epinephrine and higher norepinephrine production than control rats. Metyrapone increased TH protein synthesis and TH mRNA expression whereas its administration did not affect PNMT mRNA expression. Dexamethasone restored plasma and adrenal epinephrine concentrations and increased PNMT mRNA levels, which is consistent with an absolute requirement of glucocorticoids for PNMT expression. Adrenal denervation completely abolished the metyrapone‐induced TH mRNA expression. Blockage of cholinergic neurotransmission by nicotinic or muscarinic receptor antagonists did not prevent the metyrapone‐induced rise in TH mRNA. Finally, pituitary adenylate cyclase activating polypeptide (PACAP) adrenal content was not affected by metyrapone. These results provide evidence that metyrapone‐induced corticosterone depletion elicits transsynaptic TH activation, implying noncholinergic neurotransmission. This may involve neuropeptides other than PACAP.
Mechanisms of Cytosolic Ca2+ Suppression By Prostaglandin E2 Receptors in Rat Melanotrophs
Authors: Nagata T. , Harayama N. , Sasaki N. , Inoue M. , Tanaka K. , Toyohira Y. , Uezono Y. , Maruyama T. , Yanagihara N. , Ueta Y. , Shibuya I. 
Published: March 2003

AbstractWe have previously reported that voltage‐dependent Ca2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E2 (PGE2). In this study, mechanisms involved in the inhibitory actions of PGE2 receptors of rat melanotrophs were analysed using reverse transcriptase‐polymerase chain reaction (RT‐PCR), Ca2+‐imaging and whole‐cell, patch‐clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP1–4). PGE2 reversibly suppressed the cytosolic Ca2+ concentration ([Ca2+]i). The maximum reduction in [Ca2+]i by PGE2 was comparable to that by dopamine or to that by extracellular Ca2+ removal. RT‐PCR analysis of all four EP receptors revealed that EP3 and EP4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE2 to suppress [Ca2+]i were mimicked by the selective EP3 agonist, ONO‐AE‐248, whereas three other EP agonists, ONO‐DI‐004 (EP1), ONO‐AE1‐259 (EP2) and ONO‐AE1‐329 (EP4), had little or no effect on [Ca2+]i. All four G‐protein activated inward rectifying K+ (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT‐PCR. Dopamine concentration‐dependently activated GIRK currents, whereas PGE2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE2 acts on EP3 receptors to suppress Ca2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE2.
The Anti‐Inflammatory Effect of Bee Venom Stimulation in a Mouse Air Pouch Model Is Mediated by Adrenal Medullary Activity
Authors: Kwon Y.‐B. , Kim H.‐W. , Ham T.‐W. , Yoon S.‐Y. , Roh D.‐H. , Han H.‐J. , Beitz A.‐J. , Yang I.‐S. , Lee J.‐H. 
Published: March 2003

AbstractCutaneous electrical or chemical stimulation can produce an anti‐inflammatory effect, which is dependent on adrenal medullary‐sympathetic activation. We have previously shown that peripheral injection of bee venom (BV) also produces a significant anti‐inflammatory effect that is neurally mediated. In the present study, we examined whether this anti‐inflammatory effect is also dependent on the adrenal gland using the mouse inflammatory air pouch model. Subcutaneous (s.c.) BV injection produced a marked suppression of leucocyte migration and tumour necrosis factor (TNF)‐α concentration induced by zymosan injection into the air pouch. The role of the adrenal gland in this suppression was evaluated in adrenalectomized mice. Adrenalectomy significantly reversed the suppression of leucocyte migration and TNF‐α elevation caused by BV. Serum concentrations of corticosteroid were increased in mice with zymosan‐induced air‐pouch inflammation and this increase was reduced by BV administration, suggesting that adrenal corticosteroid release is not involved in mediating the anti‐inflammatory effects of BV. To test this hypothesis, the corticosteroid receptor antagonist (RU486) was administered and found not to affect the BV‐induced inhibition of leucocyte migration. By contrast, pretreatment with the β‐adrenergic antagonist propranolol reversed the BV‐induced inhibitory effect on leucocyte migration. These results suggest that the anti‐inflammatory effect of s.c. BV administration is mediated in part by the release of catecholamines from the adrenal medulla.