bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of acute renal failure
Authors: Fry A C , Farrington K
Published: February 2006

Acute renal failure is a common condition, frequently encountered in both community practice and hospital inpatients. While it remains a heterologous condition, following basic principles makes investigation straightforward, and initial management follows a standard pathway in most patients. This article shows this, advises on therapeutic strategies, including those in special situations, and should help the clinician in deciding when to refer to a nephrologist, and when to consider renal replacement therapy.
Kidney plays a major role in ammonia homeostasis after portasystemic shunting in patients with cirrhosis
Authors: Olde Damink Steven W. M. , Dejong Cornelis H. C. , Deutz Nicolaas E. P. , Redhead Doris N. , Hayes Peter C. , Soeters Peter B. , Jalan Rajiv
Published: February 2006

The kidney plays an important role in ammonia metabolism. In this study the hypothesis was tested that the kidney can acutely diminish ammonia release after portacaval shunting. Thirteen patients with cirrhosis (6 female/7 male, age 54.4 ± 3.3 yr) were studied. Blood was sampled prior to and 1 h after transjugular intrahepatic stent-shunt (TIPSS) insertion from the portal vein, a hepatic vein, the right renal vein, and the femoral vein, and renal and liver plasma flow were measured. Prior to TIPSS, renal ammonia release was significantly higher than ammonia release from the splanchnic region, which was not significantly different from zero. TIPSS insertion did not change arterial ammonia concentration or ammonia release from the splanchnic region but reduced renal ammonia release into the circulation ( P < 0.05) to values that were not different from zero. TIPSS resulted in a tendency toward increased venous-arterial ammonia concentration differences across leg muscle. Post-TIPSS ammonia efflux via portasystemic shunts was estimated to be seven times higher than renal efflux. Kidneys have the ability to acutely diminish systemic ammonia release after portacaval shunting. Diminished renal ammonia release and enhanced muscle ammonia uptake are important mechanisms by which the cirrhotic patient maintains ammonia homeostasis after portasystemic shunting.
A targeted apoB38.9 mutation in mice is associated with reduced hepatic cholesterol synthesis and enhanced lipid peroxidation
Authors: Lin Xiaobo , Chen Zhouji , Yue Pin , Averna Maurizio R. , Ostlund Richard E. , Watson Mark A. , Schonfeld Gustav
Published: February 2006

Familial hypobetalipoproteinemia (FHBL) due to truncation-specifying mutations of apolipoprotein B (apoB), which impair hepatic lipid export in very low-density lipoprotein (VLDL) particles, is associated with fatty liver. In an FHBL-like mouse with the apoB38.9 mutation, fatty liver develops despite reduced hepatic fatty acid synthesis. However, hepatic cholesterol contents in apoB38.9 mice are normal. We found that cholesterogenic enzymes (3-hydroxy-3-methylglutaryl-coenzyme A reductase, sterol-C5-desaturase, and 7-dehydrocholesterol reductase) were consistently downregulated in two separate expression-profiling experiments using a total of 19 mice ( n = 7 each for apob+/+and apob+/38.9, and n = 5 for apob38.9/38.9) and Affymetrix Mu74Av2 GeneChip microarrays. Results were confirmed by real-time PCR. Cholesterol synthesis rates in cultured hepatocytes were reduced by 35% and 25% in apob38.9/38.9and apob+/38.9, respectively, vs. apob+/+. Hepatic triglycerides and lipid peroxides, the latter measured by thiobarbituric acid-reactive substances (TBARS) assay, were significantly elevated in apob+/38.9(117%) and apob38.9/38.9(132%) vs. apob+/+(100%), as were mRNA expression of the microsomal lipid peroxidizing enzymes Cyp4A10 and Cyp4A14. Hepatic lipid peroxide levels were positively correlated with triglyceride contents ( r = 0.601, P = 0.0065). Thus the fatty liver due to a VLDL secretion defect is associated with insufficient adaptation to triglyceride accumulation and with increased lipid peroxidation. In contrast, apoB38.9 mice effectively maintain cholesterol homeostasis in the liver, at least in part, by reducing hepatic cholesterol synthesis.
Hepatic cytochrome P-450 reductase-null mice show reduced transcriptional response to quercetin and reveal physiological homeostasis between jejunum and liver
Authors: Mutch David M. , Crespy Vanessa , Clough Jennifer , Henderson Colin J. , Lariani Sofiane , Mansourian Robert , Moulin Julie , Wolf C. Roland , Williamson Gary
Published: February 2006

Using mice deficient in hepatic cytochrome P-450 oxidoreductase (POR), which disables the liver cytochrome P-450 system, we examined the metabolism and biological response of the anticarcinogenic flavonoid, quercetin. Profiling circulating metabolites revealed similar profiles over 72 h in wild-type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that two- to threefold more genes responded significantly to quercetin in WT compared with KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling, and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism was predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase 1 detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction.
Mechanistic basis of differences in Ca2+-handling properties of sarcoplasmic reticulum in right and left ventricles of normal rat myocardium
Authors: Sathish V. , Xu A. , Karmazyn M. , Sims S. M. , Narayanan N.
Published: February 2006

This study investigated Ca2+-cycling properties of sarcoplasmic reticulum (SR) in right ventricle (RV) and left ventricle (LV) of normal rat myocardium. Intracellular Ca2+transients and contractile function were monitored in freshly isolated myocytes from RV and LV. SR in RV displayed nearly fourfold lower rates of ATP-energized Ca2+uptake in vitro than SR of LV. The Ca2+concentration required for half-maximal activation of Ca2+transport was nearly twofold higher in SR of RV. The lower Ca2+-sequestering activity of SR in RV was accompanied by a matching decrement in Ca2+-induced phosphoenzyme formation during the catalytic cycle of the Ca2+-pumping ATPase (SERCA2). Western immunoblot analysis showed that protein levels of Ca2+-ATPase and its inhibitor phospholamban (PLN) were only ∼15% lower in SR of RV than in SR of LV. Coimmunoprecipitation experiments revealed that PLN-bound, functionally inert Ca2+-ATPase molecules in SR of RV greatly exceed (>50%) that in SR of LV. Endogenous Ca2+/calmodulin-dependent protein kinase-mediated phosphorylation of SR substrates did not abolish the huge disparity in SR Ca2+pump function between RV and LV. Intracellular Ca2+transients, evoked by electrical field stimulation, were significantly prolonged in RV myocytes compared with LV myocytes, mainly because of slow decay of intracellular Ca2+concentration. The slow decay of intracellular Ca2+concentration in RV and consequent decrease in the speed of RV relaxation may promote temporal synchrony of the end of diastole in RV and LV. The preponderance of functionally silent SR Ca2+pumps in RV reflects a higher diastolic reserve required to protect and maintain RV function in the face of a sudden rise in afterload or resistance in the pulmonary circulation.
The dorsal vagal complex as a site for cocaine- and amphetamine-regulated transcript peptide to suppress gastric emptying
Authors: Smedh Ulrika , Moran Timothy H.
Published: February 2006

Cocaine- and amphetamine-regulated transcript-derived peptides (CARTp) and corticotropin-releasing factor (CRF) alter feeding and gastrointestinal function after central administration, and the gastric inhibitory effects are mediated through CRF. We hypothesized that dorsal hindbrain effects of CARTp on gastric emptying are mediated by the vagus nerve and that the dorsal vagal complex (DVC) is a site of action for the gastric inhibitory effects of both CARTp and CRF. Rats were equipped with chronic intragastric fistulas and guide cannulas aimed at the fourth ventricle or the DVC. Fourth intracerebroventricular CARTp-induced suppression of 12 ml glucose (12.5%) gastric emptying during fill was blocked by subdiaphragmatic vagotomy. To establish whether the DVC may be a site of action for CARTp and/or CRF, intraparenchymal microinjections (0.25 μl) of CARTp (0.1 and 0.5 μg) and CRF (5 and 10 pmol) were administered in the DVC. Each dose, previously shown to be ineffective after fourth intracerebroventricular administration, suppressed gastric emptying during gastric fill vs. vehicle, but neither peptide changed gastric secretion volume or gastric acidity. The results indicate that the DVC is a target site for CRF and CARTp to inhibit gastric emptying and that the vagus mediates dorsal hindbrain effects of CARTp on gastric motor function.
Evoked response potential markers for anesthetic and behavioral states
Authors: Rojas Manuel J. , Navas Jinna A. , Rector David M.
Published: February 2006

The rodent whisker sensory system is a commonly used model of cortical processing; however, anesthetics cause profound differences in the shape and timing of evoked responses. Evoked response studies, especially those that use spatial mapping techniques, such as fMRI or optical imaging, will thus show significantly different results depending on the anesthesia used. To describe the effect of behavioral states and commonly used anesthetics, we characterized the early surface-evoked response potentials (ERPs) components (first ERP peak: gamma band 25–45 Hz; fast oscillation: 200–400 Hz; and very fast oscillation: 400–600 Hz) using a 25-channel electrode array on the somatosensory cortex during whisker stimulation. We found significant differences in the ERP shape when ketamine/xylazine, urethane, propofol, isoflurane, and pentobarbital sodium were administered and during sleep and wake states. The highest ERP amplitudes were observed under propofol anesthesia and during quiet sleep. Under isoflurane, the ERP was nearly absent, except for a very late component, which was concombinant with burst synchronization. The slowest responses were seen under urethane and propofol anesthesia. Spatial mapping experiments that use electrical, NMR, or optical techniques must consider the anesthetic dependency of these signals, especially when stimulation protocols or electrical and metabolic responses are compared.
Regulation of components of the brain and cardiac renin-angiotensin systems by 17β-estradiol after myocardial infarction in female rats
Authors: Dean Stephanie A. , Tan Junhui , White Roselyn , O’Brien Edward R. , Leenen Frans H. H.
Published: February 2006

The present study tested the hypothesis that 17β-estradiol (E2) inhibits increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Age-matched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX + subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2–3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20–40%) in OVX + high-E2 MI rats, somewhat less (10–15%) in ovary-intact MI rats, and least (<10–15%) in OVX + Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher (<20%) in OVX + Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.
Interleukin-1 mediates endothelin-1-induced fever and prostaglandin production in the preoptic area of rats
Authors: Fabricio Aline S. C. , Tringali Giuseppe , Pozzoli Giacomo , Melo Miriam C. , Vercesi Juliana A. , Souza Gloria E. P. , Navarra Pierluigi
Published: February 2006

The intracerebroventricular injection of endothelin-1 (ET-1) induces fever and increases PG levels in the cerebrospinal fluid of rats. Likewise, the injection of IL-1 into the preoptic area (POA) of the rat hypothalamus causes both fever and increased PG production. In this study, we conducted in vivo and in vitro experiments in the rat to investigate 1) the hypothalamic region involved in ET-1-induced fever and PG biosynthesis and 2) whether hypothalamic IL-1 plays a role as a mediator of the above ET-1 activities. One hundred femtomoles of ET-1 increased body temperature when injected in the POA of conscious Wistar rats; this effect was significantly counteracted by the coinjection of 600 pmol IL-1 receptor antagonist (IL-1ra). In experiments on rat hypothalamic explants, 100 nM ET-1 caused a significant increase in PGE2production and release from the whole hypothalamus and from the isolated POA, but not from the retrochiasmatic region, in 1-h incubations. Six nanomoles of IL-1ra or 10 nM of a cell-permeable interleukin-1 converting enzyme inhibitor completely counteracted the effect of ET-1 on PGE2release from the POA. One hundred nanomoles ET-1 also caused a significant increase in IL-1β immunoreactivity released into the bath solution of hypothalamic explants after 1 h of incubation, although during such time ET-1 failed to modify the gene expression of IL-1β and other pyrogenic cytokines within the hypothalamus. In conclusion, our results show that ET-1 increases IL-1 production in the POA, and this effect appears to be correlated to ET-1-induced fever in vivo, as well as to PG production in vitro.
The hydroosmotic response of frog urinary bladder to serosal hypertonicity is dependent on adenylate cyclase for its maintenance and affected by [Cl−]ochanges
Authors: Hanna-Mitchell Ann T. , Gebruers Elizabeth M.
Published: February 2006

The role of adenylate cyclase (AC) in the maintenance of the hydroosmotic response to serosal hypertonicity (SH) in anuran urinary bladder is disputed. In this study, norepinephrine (NE) significantly reversed the hydroosmotic response of Rana temporaria bladders in hypertonic medium (330 mosmol/kgH2O). The reversal was inhibited by yohimbine but was unaffected by prazosin and propranolol, indicating that NE action was mediated via α2-adrenergic receptors. Preincubation of bladders with indomethacin did not interfere with the inhibitory action of NE, contraindicating a role for prostaglandins. The SH hydroosmotic response was abolished in the presence of 5- n-ethyl- N-isopropyl amiloride (EIPA), but the antidiuretic hormone (ADH) hydroosmotic response was not. EIPA inhibits Na+/H+, known to be activated by cell shrinkage. An investigation of the anionic requirement of the SH hydroosmotic response revealed that replacement of bath Cl−with the nonpermeable anion gluconate reversibly abolished this response. In contrast, the hydroosmotic response to ADH was unaffected by Cl−removal; however, when Cl−was absent, it was no longer augmented in hypertonic bath. The SH response was inhibited by the Cl−channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate but not by the Na/K/2Cl inhibitor bumetanide. Our results show that not only the onset but also the maintenance of the SH hydroosmotic response is dependent on AC activity and does not differ in this respect to the ADH hydroosmotic response. The effect of modifying extracellular Cl−concentration, suggests that this anion, possibly functionally linked with Na+/H+activity, may be involved in invoking the SH hydroosmotic response in anuran urinary bladder.
Treatment of rats with calpain inhibitors prevents sepsis-induced muscle proteolysis independent of atrogin-1/MAFbx and MuRF1 expression
Authors: Fareed Moin U. , Evenson Amy R. , Wei Wei , Menconi Michael , Poylin Vitaliy , Petkova Victoria , Pignol Bernadette , Hasselgren Per-Olof
Published: February 2006

Muscle wasting in sepsis is a significant clinical problem because it results in muscle weakness and fatigue that may delay ambulation and increase the risk for thromboembolic and pulmonary complications. Treatments aimed at preventing or reducing muscle wasting in sepsis, therefore, may have important clinical implications. Recent studies suggest that sepsis-induced muscle proteolysis may be initiated by calpain-dependent release of myofilaments from the sarcomere, followed by ubiquitination and degradation of the myofilaments by the 26S proteasome. In the present experiments, treatment of rats with one of the calpain inhibitors calpeptin or BN82270 inhibited protein breakdown in muscles from rats made septic by cecal ligation and puncture. The inhibition of protein breakdown was not accompanied by reduced expression of the ubiquitin ligases atrogin-1/MAFbx and MuRF1, suggesting that the ubiquitin-proteasome system is regulated independent of the calpain system in septic muscle. When incubated muscles were treated in vitro with calpain inhibitor, protein breakdown rates and calpain activity were reduced, consistent with a direct effect in skeletal muscle. Additional experiments suggested that the effects of BN82270 on muscle protein breakdown may, in part, reflect inhibited cathepsin L activity, in addition to inhibited calpain activity. When cultured myoblasts were transfected with a plasmid expressing the endogenous calpain inhibitor calpastatin, the increased protein breakdown rates in dexamethasone-treated myoblasts were reduced, supporting a role of calpain activity in atrophying muscle. The present results suggest that treatment with calpain inhibitors may prevent sepsis-induced muscle wasting.
FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene expression without modulating the other (an)orexigenic neuropeptides in chickens
Authors: Dridi Sami , Ververken Cedric , Hillgartner F. Bradley , Lutgarde Arckens , Van der Gucht Estel , Cnops Lieselotte , Decuypere Eddy , Buyse Johan
Published: February 2006

Cerulenin, a natural fatty acid synthase (FAS) inhibitor, and its synthetic analog C75 are hypothesized to alter the metabolism of neurons in the hypothalamus that regulate ingestive behavior to cause a profound decrease of food intake and an increase in metabolic rate, leading to body weight loss. The bulk of data exclusively originates from mammals (rodents); however, such effects are currently lacking in nonmammalian species. We have, therefore, addressed this issue in broiler chickens because this species is selected for high growth rate and high food intake and is prone to obesity. First, we demonstrate that FAS messenger and protein are expressed in the hypothalamus of chickens. FAS immunoreactivity was detected in a number of brain regions, including the nucleus paraventricularis magnocellularis and the nucleus infundibuli hypothalami, the avian equivalent of the mammalian arcuate nucleus, suggesting that FAS may be involved in the regulation of food intake. Second, we show that hypothalamic FAS gene expression was significantly ( P < 0.05) decreased by overnight fasting similar to that in liver, indicating that hypothalamic FAS gene is regulated by energy status in chickens. Finally, to investigate the physiological consequences of in vivo inhibition of fatty acid synthesis on food intake, we administered cerulenin by intravenous injections (15 mg/kg) to 2-wk-old broiler chickens. Cerulenin administration significantly reduced food intake by 23 to 34% ( P < 0.05 to P < 0.0001) and downregulated FAS and melanocortin receptors 1, 4, and 5 gene expression ( P < 0.05). However, the known orexigenic (neuropeptide Y, agouti gene-related peptide, orexin, and orexin receptor) and anorexigenic (pro-opiomelanocortin and corticotropin-releasing hormone) neuropeptide mRNA levels remained unchanged after cerulenin treatment. These results suggest that the catabolic effect of cerulenin in chickens may be mediated through the melanocortin system rather than the other neuropeptides known to be involved in food intake regulation.
Products of heme oxygenase and their potential therapeutic applications
Authors: Kirkby Kristin A. , Adin Christopher A.
Published: February 2006

Heme oxygenase 1 (HO-1) is induced in response to cellular stress and is responsible for converting the prooxidant heme molecule into equimolar quantities of biliverdin (BV), carbon monoxide (CO), and iron. BV is then converted to bilirubin (BR) by the enzyme biliverdin reductase. Experimental evidence suggests that induction of the HO system is an important endogenous mechanism for cytoprotection and that the downstream products of heme degradation, CO, BR, and BV, may mediate these powerful beneficial effects. These molecules, which were once considered to be toxic metabolic waste products, have recently been shown to have dose-dependent vasodilatory, antioxidant, and anti-inflammatory properties that are particularly desirable for tissue protection during organ transplantation. In fact, recent work has demonstrated that administration of exogenous CO, BR, or BV may offer a simple, inexpensive method to substitute for the cytoprotective effects of HO-1 in a variety of clinically applicable models. This review will attempt to summarize the relevant biochemical and cytoprotective properties of CO, BR, and BV, and will discuss emerging studies involving the therapeutic applications of these molecules in the kidney and other organ systems.
SLC4 base (HCO3−, CO32−) transporters: classification, function, structure, genetic diseases, and knockout models
Authors: Pushkin Alexander , Kurtz Ira
Published: February 2006

In prokaryotic and eukaryotic organisms, biochemical and physiological processes are sensitive to changes in H+activity. For these processes to function optimally, a variety of proteins have evolved that transport H+/base equivalents across cell and organelle membranes, thereby maintaining the pH of various intracellular and extracellular compartments within specific limits. The SLC4 family of base (HCO3−, CO32−) transport proteins plays an essential role in mediating Na+- and/or Cl−-dependent base transport in various tissues and cell types in mammals. In addition to pH regulation, specific members of this family also contribute to vectorial transepithelial base transport in several organ systems including the kidney, pancreas, and eye. The importance of these transporters in mammalian cell biology is highlighted by the phenotypic abnormalities resulting from spontaneous SLC4 mutations in humans and targeted deletions in murine knockout models. This review focuses on recent advances in our understanding of the molecular organization and functional properties of SLC4 transporters and their role in disease.
Calf muscle-tendon properties and postural balance in old age
Authors: Onambele Gladys L. , Narici Marco V. , Maganaris Constantinos N.
Published: February 2006

We tested the hypothesis that compromised postural balance in older subjects is associated with changes in calf muscle-tendon physiological and mechanical properties. Trial duration and center of pressure (COP) displacements were measured in 24 younger (aged 24 ± 1 yr), 10 middle-aged (aged 46 ± 1 yr), and 36 older (aged 68 ± 1 yr) healthy subjects under varying levels of postural difficulty. Muscle-tendon characteristics were assessed by dynamometry, twitch superimposition, and ultrasonography. In tandem and single-leg stances, trial duration decreased (≤65% lower, P < 0.001) and COP displacements increased (≤90% higher, P < 0.05) with age. Muscle strength, size, activation capacity, and tendon mechanical properties decreased with age by 55, 13, 13, and 36–48%, respectively ( P < 0.05). Regressions with these parameters and balance indexes were significant ( P < 0.05) for single-leg and tandem (0.69 < r2< 0.90) postures only, indicating that the age-related changes in muscle-tendon characteristics may explain the majority of the variance in balance performance during tasks more difficult than habitual bipedal stance.
Serum IGF-I and IGFBP-3 Levels of Turkish Children during Childhood and Adolescence: Establishment of Reference Ranges with Emphasis on Puberty
Authors: Bereket Abdullah , Turan Serap , Omar Anjumanara , Berber Mustafa , Ozen Ahmet , Akbenlioglu Cengiz , Haklar Goncagul
Published: February 2006

Aims/Methods: We established age- and sex-related reference ranges for serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls), and constructed a model for calculation of standard deviation scores of IGF-I and IGFBP-3 according to age, sex and pubertal stage. Results: Serum IGF-I and IGFBP-3 concentrations tended to be higher in girls compared to boys of the same ages, but the differences were statistically significant only in pubertal ages (9–14 years) for IGF-I and only in prepubertal ages for IGFBP-3 (6–8 years) (p < 0.05). Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15 years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage followed by a rapid increase in IGF-I in the early pubertal stages. A relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at age 10–11 years in girls and at 12–13 years in boys which preceded the reported age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3 either did not change or decreased by increasing age. Interrelationships between growth factors and anthropometric measurements have been described, and the physiologic consequences of these have been discussed in detail. Conclusions: Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those reported in other studies emphasize the importance of locally established reference ranges. Establishment of this reference data and a standard deviation score prediction model based on age, sex and puberty will enhance the diagnostic power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our population.
Liquorice in Moderate Doses Does Not Affect Sex Steroid Hormones of Biological Importance although the Effect Differs between the Genders
Authors: Sigurjonsdottir Helga Agusta , Axelson Magnus , Johannsson Gudmundur , Manhem Karin , Nyström Ernst , Wallerstedt Sven
Published: February 2006

Background/Aim: Liquorice is commonly consumed, at least in the western world, and we have earlier shown that even moderate doses of liquorice have significant effects on the cortisol metabolism by inhibiting 11β-hydroxysteroid dehydrogenase type 2. The suggestion that liquorice decreases the testosterone levels in men makes it vital to study the effect of moderate doses of liquorice on sex steroid hormones. Methods: Fifteen women and 21 men (healthy volunteers and subjects with essential hypertension) consumed 100 g of liquorice (150 mg glycyrrhetinic acid) daily in a 9-week, open-treatment trial. Blood and 24-hour urine samples were collected for hormone analysis before and after 4 weeks of liquorice consumption and 4 weeks after cessation of liquorice intake. Results: The liquorice induced a moderate decrease in the serum concentrations of dehydroepiandrostenedione sulphate in men (p = 0.002). The relative change in serum levels of dehydroepiandrosterone sulphate differed between the genders (p = 0.03). No significant changes were observed in the serum testosterone levels after 4 weeks of liquorice consumption, and the urine excretion of androgens (etiocholanolone and androstenedione) did not change. Conclusions: Liquorice in moderate doses primarily affects the cortisol metabolism and only marginally the androgen hormones. Gender may influence the action of liquorice.
Improving the Management of Anemia in Hemodialysis Patients by Implementing the Continuous Quality Improvement Program
Authors: Chen Min , Deng Jin-Hua , Zhou Fu-De , Wang Mei , Wang Hai-Yan
Published: February 2006

Background: Anemia is common in hemodialysis patients, and improvement in anemia management is possible with the implementation of continuous quality improvement (CQI) programs. The aim of this study is to improve anemia management in chronic hemodialysis patients using CQI. Methods: Ninety hemodialysis patients in our single center were enrolled in the study. The patients were followed up from January 2004 to October 2005. The CQI team-oriented approach was driven by a process called the ‘FOCUS-PDCA cycle plan’ (find, organize, clarify, uncover, start, plan, do, check and act). Hemoglobin (Hb), serum ferritin and transferrin saturation were monitored periodically. Results: By implementation of the CQI program, the proportion of patients with Hb ≧110 g/l increased from 42.2 to 60.0% (p < 0.05), and the Hb level increased from 101.2 ± 18.05 to 110.4 ± 14.23 g/l (p < 0.0001). The proportion of patients with an adequate iron status increased from 28.0 to 53.3% (p < 0.05). Conclusion: The CQI program is a useful method in the management of anemia in hemodialysis patients.
Regulation of Intracellular Calcium Levels and Urokinase Activity in MDA MB 231 Cells by Quercetin
Authors: Devipriya S. , Vani G. , Ramamurthy N. , Shyamaladevi C.S.
Published: February 2006

Background: The common plant bioflavonoid, quercetin, is cytotoxic to various tumor cell lines, particularly breast cancer, by affecting the protein-kinase-C-dependent signal pathways and by cell cycle regulation. However, its role in breast cancer metastasis has not been studied so far. Increased uPA activity is evident in highly metastatic breast cancer, which is calcium dependent. Methods: MDA MB 231 cells were treated with various concentrations of quercetin (15–45 µg/ml). The cytotoxic effect of quercetin was assessed by MTT assay and DNA fragmentation analysis. Intracellular calcium levels were measured using Fura-2, a specific Ca2+ fluorescence indicator. Calcium uptake and release in cells treated with quercetin were measured using radioactive 45Ca2+. Urokinase enzyme activity was assayed by a casein zymogram. Results: Quercetin elicited dose- and time-dependent cytotoxicity as evidenced by the MTT assay. The maximum effect was observed at 48 h with a quercetin concentration of (45 µg/ml). DNA agarose gel electrophoresis showed dose-dependent DNA fragmentation on quercetin treatment. Quercetin caused significant depletion of cytosolic calcium levels and decreased calcium uptake from the intracellular stores. Casein zymogram showed a marked reduction of urokinase activity as evident by clear lysis bands on a dark background on treatment with quercetin. Conclusion: Quercetin was found to exhibit cytotoxicity in the highly invasive breast cancer cell line MDA MB 231 in a dose- and time-dependent manner. Quercetin inhibited calcium dependent urokinase activity and hence may prove to be an effective antimetastatic agent.
Sunflower Seed Oil-Enriched Product Can Inhibit Ehrlich Solid Tumor Growth in Mice
Authors: Silva Lucilene A. , Nascimento Kátia A.F. , Maciel Márcia C.G. , Pinheiro Mayara T. , Sousa Paulo R.A. , Ferreira Susanne C.P. , Azevedo Ana Paula S. , Guerra Rosane N.M. , Nascimento Flávia R.F.
Published: February 2006

Background: Sunflower seed oil (SSO) effect on solid and ascitic forms of Ehrlich tumor was evaluated. Methods: Solid or ascitic Ehrlich tumor-bearing Swiss mice were treated daily, by subcutaneous route, with 200 µl of SSO. The solid tumor-bearing footpad was measured every 3 days and ascitic tumor-bearing mice had their ascites collected and quantified. At the end of the SSO treatment, the total cell number in lymphoid organs was quantified. Results: Subcutaneous treatment with SSO inhibits the solid tumor growth and increases lymph node cell number in animals with solid tumor, but has no effect on animals with ascitic tumor. Conclusions: SSO can delay the solid tumor growth, possibly due to better absorption of this treatment by draining lymph nodes.
Adoptive Transfer of CD4+T Cells Reactive to Modified Low-Density Lipoprotein Aggravates Atherosclerosis
Authors: Zhou Xinghua , Robertson Anna-Karin L. , Hjerpe Charlotta , Hansson Göran K.
Published: February 2006

Objective—Atherosclerosis is associated with immune responses to oxidized low-density lipoprotein (oxLDL). The presence of activated macrophages and T cells in lesions suggests that cell-mediated immune reactions are taking place during the disease process. However, the role of specific immune responses has remained unclear. We have previously shown that transfer of CD4+T cells from apolipoprotein E knockout mice (apoE−/−) into immunodeficient apoE−/−scid/scidmice accelerates disease.

Methods and Results—To test whether this effect is dependent on specific disease-associated antigens, purified CD4+T cells from oxLDL-immunized mice were transferred into apoE−/−scid/scidmice. CD4+T cells from mice immunized with a nonrelevant antigen, keyhole limpet hemocyanin (KLH), and naïve CD4+T cells were used as controls. After 12 weeks, all mice that received T cells had larger lesions than untouched apoE−/−scid/scidcontrols. However, mice receiving CD4+T cells from oxLDL immunized mice had substantially accelerated lesion progression compared with those receiving naive or KLH-primed T cells. Circulating levels of interferon-γ were increased in proportion to the acceleration of atherosclerosis.

Conclusion—These data show that adoptive transfer of purified CD4+ T cells from oxLDL-immunized mice accelerates atherosclerosis. They support the notion that Th1 cellular immunity is proatherogenic and identify oxLDL as a culprit autoantigen.
Role of Circulating Vascular Progenitors in Angiogenesis, Vascular Healing, and Pulmonary Hypertension
Authors: Sata Masataka
Published: February 2006

Accumulating evidence suggests that circulating progenitors contribute to vascular healing and remodeling under physiological and pathological conditions. Although there is growing enthusiasm for therapeutic and diagnostic application of bone marrow–derived progenitors, there are concerns that transplanted precursors or bone marrow cells may participate in the pathogenesis of unfavorable diseases such as cancer, retinopathy, and atherosclerosis. This review summarizes recent findings obtained from animal models to examine the roles of circulating vascular progenitor cells in angiogenesis, pulmonary hypertension, and vascular healing.
Comparison of Circulating Adiponectin and Proinflammatory Markers Regarding Their Association With Metabolic Syndrome in Japanese Men
Authors: Matsushita Kunihiro , Yatsuya Hiroshi , Tamakoshi Koji , Wada Keiko , Otsuka Rei , Takefuji Seiko , Sugiura Kaichiro , Kondo Takahisa , Murohara Toyoaki , Toyoshima Hideaki
Published: February 2006

Background—

Anti-inflammatory and proinflammatory molecules purportedly play an important role in developing metabolic syndrome (MetS). However, little is known as to the relative importance of these molecules in the association with MetS.

Methods and Results—

We studied 624 middle-aged Japanese men without medical history of cardiovascular disease or cancer and investigated the associations of circulating tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and adiponectin with MetS. We used the respective definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (ATP-III), the International Diabetes Federation, and the Japanese Society of Internal Medicine. Decreased serum adiponectin was observed in those with any of the ATP-III–MetS components, whereas this was not the case with increased TNF-α, IL-6, or CRP. Adiponectin and CRP levels linearly deteriorated with an increasing number of ATP-III–MetS components (trend
P
<0.001, respectively). Significantly higher CRP and lower adiponectin levels were observed in those who met any MetS criteria, whereas increased TNF-α was observed in only those with ATP-III–MetS. Finally, odds ratios (ORs) for MetS prevalence of a 1-SD increase/decrease in log-transformed 4 markers were calculated with multivariate logistic regression analyses. Consequently, decreased adiponectin was associated most strongly with ATP-III–MetS (adiponectin: OR, 1.90 [95% CI, 1.44 to 2.51];
P
<0.001; CRP: OR, 1.33 [95% CI, 1.01 to 1.74];
P
=0.03; TNF-α: OR, 1.25 [95% CI, 0.94 to 1.67];
P
=0.12; and IL-6: OR, 0.87 [95% CI, 0.63 to 1.19];
P
=0.37). This result was not altered by using the other 2 criteria.

Conclusions—

The present results raise the possibility that decreased serum adiponectin might be fundamentally involved in the development of MetS.
Macrophage ATP-Binding Cassette Transporter A1 Overexpression Inhibits Atherosclerotic Lesion Progression in Low-Density Lipoprotein Receptor Knockout Mice
Authors: Van Eck Miranda , Singaraja Roshni R. , Ye Dan , Hildebrand Reeni B. , James Erick R. , Hayden Michael R. , Van Berkel Theo J.C.
Published: February 2006

Background—

ATP-binding cassette transporter A1 (ABCA1) is a key regulator of cellular cholesterol and phospholipid transport. Previously, we have shown that inactivation of macrophage ABCA1 induces atherosclerosis in low-density lipoprotein receptor knockout (LDLr−/−) mice. However, the possibly beneficial effects of specific upregulation of macrophage ABCA1 on atherogenesis are still unknown.

Methods and Results—

Chimeras that specifically overexpress ABCA1 in macrophages were generated by transplantation of bone marrow from human ABCA1 bacterial artificial chromosome (BAC) transgenic mice into LDLr−/− mice. Peritoneal macrophages isolated from the ABCA1 BAC → LDLr−/− chimeras exhibited a 60% (
P
=0.0006) increase in cholesterol efflux to apolipoprotein AI. To induce atherosclerosis, the mice were fed a Western-type diet containing 0.25% cholesterol and 15% fat for 9, 12, and 15 weeks, allowing analysis of effects on initial lesion development as well as advanced lesions. No significant effect of macrophage ABCA1 overexpression was observed on atherosclerotic lesion size after 9 weeks on the Western-type diet (245±36×10
3
μm
2
in ABCA1 BAC → LDLr−/− mice versus 210±20×10
3
μm
2
in controls). However, after 12 weeks, the mean atherosclerotic lesion area in ABCA1 BAC → LDLr−/− mice remained only 164±15×10
3
μm
2
(
P
=0.0008) compared with 513±56×10
3
μm
2
in controls (3.1-fold lower). Also, after 15 weeks on the diet, lesions in mice transplanted with ABCA1 overexpressing bone marrow were still 1.6-fold smaller (393±27×10
3
μm
2
compared with 640±59×10
3
μm
2
in control transplanted mice;
P
=0.0015).

Conclusion—

ABCA1 upregulation in macrophages inhibits the progression of atherosclerotic lesions.
Platelet-Derived Growth Factor BB–Mediated Normalization of Dermal Interstitial Fluid Pressure After Mast Cell Degranulation Depends on β3 but Not β1 Integrins
Authors: Lidén Åsa , Berg Ansgar , Nedrebø Torbjørn , Reed Rolf K. , Rubin Kristofer
Published: February 2006

Interstitial fluid pressure (P
IF
) is one of the determinants of transcapillary fluid flux and thereby interstitial fluid volume. Cell-mediated control of P
IF
regulates fluid content in the loose interstitial connective tissues that surround the capillary bed. To maintain a normal P
IF
in dermis, β1 integrins mediate the tensile strength applied by connective tissue cells on the extracellular matrix. Platelet-derived growth factor (PDGF)-BB normalizes anaphylaxis-induced reduction of P
IF
. Anti–β3 integrin IgG and a cyclic RGD peptide that inhibits the αVβ3 integrin blocked the ability of PDGF-BB to normalize the lowered P
IF
resulting from mast cell degranulation. PDGF-BB was unable to normalize P
IF
lowered as a result of mast cell degranulation in β3-negative mice. Monoclonal anti–β3 integrin IgG had no effect on P
IF
in normal mouse dermis. In contrast, administration of anti–β1 integrin IgM lowered P
IF
in normal dermis but had no effect on PDGF-BB–induced normalization of P
IF
after anaphylaxis. Furthermore, collagen gel contraction mediated by wild-type mouse embryonal fibroblasts were only marginally affected by function-blocking anti–β1 integrin antibodies, especially in the presence of PDGF-BB. In contrast, contraction mediated by αV-negative mouse embryonic fibroblasts was completely blocked by anti–β1 integrin antibodies, even after stimulation with PDGF-BB. These results show a previously unrecognized in vivo function for the αVβ3 integrin, as a participant in the control of P
IF
during inflammatory reactions. Furthermore, our data demonstrate that PDGF-BB induces connective tissue cells to generate tensile forces via αVβ3 during such reactions.
Role of CT Angiography in Thrombolysis Decision-Making for Patients With Presumed Seizure at Stroke Onset
Authors: Sylaja P.N. , Dzialowski Imanuel , Krol Andrea , Roy Jayanta , Federico Paolo , Demchuk Andrew M. ,   Calgary Stroke Program
Published: February 2006

Background and Purpose—

The presence of seizure at stroke onset is a contraindication for intravenous tissue plasminogen activator treatment. A significant proportion of these patients’ deficits are not attributable to Todd’s paralysis and could be attributable to reversible ischemia. Currently there are no established methods of differentiating Todd’s paralysis from ischemic stroke/early seizure. We sought to determine whether computed tomographic angiography (CTA) can be helpful in differentiating the 2.

Methods—

Three hundred and twenty six patients underwent noncontrast CT and CTA for acute stroke at our institution over 3 years (June 2002 to April 2005). Of them, 116 had disabling deficits and presented within 3 hours. We reviewed the clinical data, noncontrast CT, CTA, electroencephalogram and outcome of these patients and identified those who presented with presumed seizure activity at stroke onset (seizure or altered consciousness at stroke onset).

Results—

Nine (7.7%) patients had a concern of seizure at stroke onset. Median age 73 years (range, 31 to 85 years), median National Institutes of Health Stroke Scale (NIHSS) score 12 (range, 5 to 29). CTA showed proximal middle cerebral artery occlusion in 2 and distal middle cerebral artery occlusion in 3 patients. All 5 of these patients had evidence of infarction on follow-up (stroke+early seizure group-intracranial occlusion present). Three of these patients received intravenous tissue plasminogen activator because they were deemed to have “ischemic tissue at risk”. Four patients had normal CT and CTA studies and recovered completely in 24 hours (Todd’s paralysis only group-intracranial occlusion negative).

Conclusion—

Seizure at stroke onset was relatively uncommon in a consecutive cohort of acute stroke patients. CTA was a useful modality in differentiating Todd’s paralysis from early seizure and ischemia by detection of intracranial occlusion and may contribute to decision-making for thrombolysis.
Peroxynitrite Diminishes Myogenic Activity and Is Associated With Decreased Vascular Smooth Muscle F-Actin in Rat Posterior Cerebral Arteries
Authors: Maneen Matthew J. , Hannah Rachael , Vitullo Lisa , DeLance Nicole , Cipolla Marilyn J.
Published: February 2006

Background and Purpose—

This study investigated the effect of peroxynitrite (ONOO
−
) on pressure-induced myogenic activity and vascular smooth muscle (VSM) actin of isolated posterior cerebral arteries (PCAs).

Methods—

Histochemical staining of nitrotyrosine (NT) was used to demonstrate the presence of ONOO
−
in the cerebrovasculature after 1 hour of middle cerebral artery occlusion with 30 minutes of reperfusion. To determine the effect of ONOO
−
on pressure-induced myogenic activity, third-order PCAs from nonischemic animals were isolated and mounted in an arteriograph chamber. Diameter in response to changes in pressure was determined in the absence and presence of ONOO
−
(10
−8
to 10
−4
mol/L). Filamentous actin (F-actin) and globular actin (G-actin) were quantified using confocal microscopy in PCAs with and without exposure to ONOO
−
.

Results—

NT staining of vascular cells was greater in ischemic brain versus sham animals (56±3% versus 35±3%;
P
<0.01). Addition of low concentrations of ONOO
−
(≤10
−6
mol/L) to isolated PCAs caused constriction from 129±16 μm to 115±15 μm (
P
<0.01), whereas concentrations >10
−6
mol/L caused dilation of spontaneous tone and loss of myogenic activity in the physiological range of 50 to 125 mm Hg, increasing diameter from 130±6 to 201±5 μm at 75 mm Hg (
P
<0.01). In addition, the diminished myogenic activity was associated with a 4.5-fold decrease in F-actin content of VSM and a 27% increase in G-actin content (
P
<0.01).

Conclusions—

This study demonstrates that ONOO
−
affects the myogenic activity of cerebral arteries and causes F-actin depolymerization in VSM, a consequence that could promote vascular damage during reperfusion injury and further brain injury.