bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semax, an analogue of adrenocorticotropin (4–10), binds specifically and increases levels of brain‐derived neurotrophic factor protein in rat basal forebrain
Authors: Dolotov Oleg V. , Karpenko Ekaterina A. , Seredenina Tamara S. , Inozemtseva Lyudmila S. , Levitskaya Natalia G. , Zolotarev Yuriy A. , Kamensky Andrey A. , Grivennikov Igor A. , Engele Juergen , Myasoedov Nikolay F. 
Published: January 2006

AbstractThe heptapeptide Semax (Met‐Glu‐His‐Phe‐Pro‐Gly‐Pro) is an analogue of the N‐terminal fragment (4–10) of adrenocorticotropic hormone which, after intranasal application, has profound effects on learning and memory formation in rodents and humans, and also exerts marked neuroprotective effects. A clue to the molecular mechanism underlying this neurotropic action was recently given by the observation that Semax stimulates the synthesis of brain‐derived neurotrophic factor (BDNF), a potent modulator of synaptic plasticity, in astrocytes cultured from rat basal forebrain. In the present study, we investigated whether Semax affects BDNF levels in rat basal forebrain upon intranasal application of the peptide. In addition, we examined whether cell membranes isolated from this brain region contained binding sites for Semax. The binding of tritium‐labelled Semax was found to be time dependent, specific and reversible. Specific Semax binding required calcium ions and was characterized by a mean± SEM dissociation constant (KD) of 2.4 ± 1.0 nm and a BMAX value of 33.5 ± 7.9 fmol/mg protein. Sandwich immunoenzymatic analysis revealed that Semax applied intranasally at 50 and 250 µg/kg bodyweight resulted in a rapid increase in BDNF levels after 3 h in the basal forebrain, but not in the cerebellum. These results point to the presence of specific binding sites for Semax in the rat basal forebrain. In addition, these findings indicate that the cognitive effects exerted by Semax might be associated, at least in part, with increased BDNF protein levels in this brain region.
Use of microarray biomarkers to identify longevity therapeutics
Authors: Spindler Stephen R. 
Published: January 2006

SummaryA number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life‐ and health‐span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life‐ and health‐span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemopreventatives in reproducing the hepatic gene‐expression profiles produced by long‐term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER‐2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene‐expression biomarkers can be used to identify promising candidate CR mimetics.
Rules for the use of model organisms in antiaging pharmacology
Authors: Jafari Mahtab , Rose Michael R. 
Published: January 2006

SummaryThe use of animal models for initially screening antiaging drugs is a promising approach for drug discovery. However, there a number of potential artifacts, confounds and errors that can arise in such research programs. The following rules are intended to minimize such problems: (1) since aging occupies an increasing proportion of human adulthood, data that conflate aging and late life should not be extrapolated to human aging; (2) the response to candidate medications should show a normal dose‐response pattern, although not necessarily a linear response; (3) medicated animal models should not be hypometabolic; (4) medicated animal models should not show pronounced reductions in fertility; (5) medicated animal models should not exhibit general nervous system depression; (6) the effect of the medication should not be highly sensitive to the culture environment; (7) the effect of the medication should not be highly dependent on the genetic ancestry of the stock employed, leaving aside inbreeding, which should be avoided because humans are not generally inbred. While these rules do not guarantee successful extrapolation of successful drug results from the animal model to humans in a clinical setting, the failure to adhere to these rules should raise doubts about such extrapolation.
Are Patient Preferences for Life‐Sustaining Treatment Really a Barrier to Hospice Enrollment for Older Adults with Serious Illness?
Authors: Casarett David , Van Ness Peter H. , O'Leary John R. , Fried Terri R. 
Published: February 2006

OBJECTIVES: To determine whether patient preferences are a barrier to hospice enrollment.DESIGN: Prospective cohort study.SETTING: Fifteen ambulatory primary care and specialty clinics and three general medicine inpatient units.PARTICIPANTS: Two hundred three seriously ill patients with cancer (n=65, 32%), congestive heart failure (n=77, 38%), and chronic obstructive pulmonary disease (n=61, 30%) completed multiple interviews over a period of up to 24 months.MEASUREMENTS: Preferences for high‐ and low‐burden life‐sustaining treatment and site of death and concern about being kept alive by machines.RESULTS: Patients were more likely to enroll in hospice after interviews at which they said that they did not want low‐burden treatment (3 patients enrolled/16 interviews at which patients did not want low‐burden treatment vs 47 patients enrolled/841 interviews at which patients wanted low‐burden treatment; relative risk (RR)=3.36, 95% confidence interval (CI)=1.17–9.66), as were interviews at which patients said they would not want high‐burden treatment (5/28 vs 45/826; RR=3.28, 95% CI=1.14–7.62), although most patients whose preferences were consistent with hospice did not enroll before the next interview. In multivariable Cox regression models, patients with noncancer diagnoses who desired low‐burden treatment (hazard ratio (HR)=0.46, 95% CI=0.33–0.68) were less likely to enroll in hospice, and those who were concerned that they would be kept alive by machines were more likely to enroll (HR=5.46, 95% CI=1.86–15.88), although in patients with cancer, neither preferences nor concerns about receiving excessive treatment were associated with hospice enrollment. Preference for site of death was not associated with hospice enrollment.CONCLUSION: Overall, few patients had treatment preferences that would make them eligible for hospice, although even in patients whose preferences were consistent with hospice, few enrolled. Efforts to improve end‐of‐life care should offer alternatives to hospice that do not require patients to give up life‐sustaining treatment, as well as interventions to improve communication about patients' preferences.
Anatomic Proximity of the Esophagus to the Coronary Sinus: Implication for Catheter Ablation Within the Coronary Sinus
Authors: TSAO HSUAN‐MING , WU MEI‐HAN , CHERN MING‐SHENG , TAI CHING‐TAI , LIN YENN‐JIANG , CHANG SHIH‐LIN , CHIANG SHUO‐JU , ONG MARY GERTRUDE , WONGCHAROEN WANWARANG , HSU NAI‐WEI , CHANG CHENG‐YEN , CHEN SHIH‐ANN 
Published: January 2006

Introduction: The anatomic proximity between the esophagus and the coronary sinus (CS) might render the esophagus vulnerable to thermal injury during ablation. Therefore, we investigated the anatomic relationship between the esophagus and the CS in patients with atrial fibrillation (AF).
Methods and Results: Thirty patients (25 males, mean age = 54 ± 11 years) with drug‐refractory paroxysmal AF were included. Sixteen‐slice multidetector computed tomography was performed to depict the course of the esophagus and relationship to the CS. The esophagus was in direct contact with the CS in 57% (17/30) of patients (group 1). The mean length of the contact was 6.1 ± 3.4 mm. In the remaining 13 patients, the esophagus did not come in direct contact with the CS (group 2). The shortest distance between the esophagus and the CS was 4.0 ± 2.6 mm. The CS diameter (9.4 ± 1.8 vs 8.5 ± 2.4 mm, P = 0.15), esophagus width (18.6 ± 1.6 vs 18.6 ± 1.7 mm, P = 0.87), anteroposterior diameter of the left atrium (35.9 ± 3.8 vs 35.0 ± 3.3 mm, P = 0.58), thickness of the anterior wall of the esophagus (2.9 ± 0.6 vs 2.9 ± 0.6 mm, P = 0.97), and shortest distance from the esophagus to the CS ostium (19.3 ± 5.4 vs 25.0 ± 6.2 mm, P = 0.02) and to the great cardiac vein (8.5 ± 5.3 vs 12.1 ± 6.9 mm, P = 0.10) were compared between the two groups.
Conclusions: In 57% of our patients, the esophagus was in direct contact with the CS, and a significantly shorter distance between the esophagus and the CS ostium was noted in these patients. It is important to prevent esophageal damage when applying energy within the CS.
Do Intramural Virtual Electrodes Facilitate Successful Defibrillation? Model‐Based Analysis of Experimental Evidence
Authors: HOOKS DARREN A. , TREW MARK L. , SMAILL BRUCE H. , PULLAN ANDREW J. 
Published: January 2006

Introduction: Recent computer model and experimental studies have suggested that microscopic intramural collagenous planes may facilitate successful defibrillation through the generation of shock‐induced virtual electrodes deep within the ventricular wall. Evidence supporting the existence of intramural virtual electrodes has been drawn from several recent studies, which map shock‐induced membrane potential (Vm) over the cut transmural surface of dissected segments of porcine left ventricle (LV). The artificially created transmural boundary in these experiments is impermeable to intracellular current. It is not known how this constraint limits the interpretation of these experiments in terms of the shock response of the intact ventricle.
Methods and Results: This study uses a realistic 3D computer model of LV myocardium to aid experimental interpretation. The model incorporates a microstructural description of intramural cleavage plane discontinuities measured by confocal microscopy of rat LV. Electrical shocks are applied across the model tissue, with and without introduced transmural boundaries. Shocks of varying strength (4–40 V/cm) are also applied to the model and the response analyzed. Results show that shock‐induced Vm changes (ΔVm) on a transmural tissue boundary are significantly different to ΔVm of the intact ventricle, and the extent of difference depends on boundary orientation. However, the presence and qualitative behavior of intramural virtual electrodes is preserved irrespective of boundary placement. The model also confirms experimental observations that most rapid transmural activation occurs for shocks of strength 5–10 V/cm. Two distinct mechanisms suppress virtual electrode propagation, and hence slow tissue activation, outside of this optimal shock strength range.
Conclusions: This study supports the hypothesis that distributed microscopic intramural virtual electrodes contribute to rapid activation of the ventricular wall during defibrillation.
Comparison of the Effects of VVI Versus DDD Pacing on Cardiac Baroreflex Function
Authors: OGINOSAWA YASUSHI , ABE HARUHIKO , YASUMASU TOMIYA , TSURUGI TAKUO , KOHNO RITSUKO 
Published: January 2006

Introduction: Conventional baroreceptor‐heart rate (HR) reflex sensitivity cannot be examined in chronotropically incompetent patients or in pacemaker recipients. However, cardiac baroreceptor reflex sensitivity (BRS)‐stroke volume (SV), which is closely and linearly correlated with BRS‐HR, may be an alternative in that population. The aim of this study was to compare the BRS‐SV in pacemaker recipients with a fixed HR paced in VVI versus DDD modes in the supine and upright positions. Methods: The pacing mode was set randomly to DDD or VVI with complete atrial and/or ventricular capture, then crossed over to the alternate mode in 9 recipients of dual‐chamber pacemakers with atrioventricular (AV) block. Beat‐to‐beat mean blood pressure and SV were measured in the supine and upright positions, using a tilt table. The BRS‐SV, expressed in %/mmHg, was the ratio of low‐frequency (LF) power to total power (TP) of SV variability, measured by spectral analysis of spontaneous variations in mean blood pressure and SV. Results: BRS‐SV was significantly lower in the VVI than in the DDD mode in the supine (37.2 ± 26.7 vs 14.5 ± 7.7%/mmHg) and upright (22.9 ± 16.9 vs 10.6 ± 6.6%/mmHg) positions (P < 0.05 for both comparisons). Conclusions: VVI pacing is adverse from the standpoint of cardiac autonomic baroreflex function. A decreased BRS‐SV may be one of the factors involved in the hemodynamic intolerance associated with VVI pacing.
Atypische klinische Manifestation einer Pigmentpurpura
Authors: Zalaudek Iris , Ferrara Gerardo , Brongo Sergio , Giorgio Caterina M. , Argenziano Giuseppe 
Published: January 2006

ZusammenfassungDer Name “Pigmentpurpura” umfasst ein Spektrum verschiedener Krankheitsbilder, die mit petechialen Blutungen einhergehen und zu umschriebenen, fleckartigen gelbbraunen Verfärbungen der Haut führen.Traditionsgemäß können 5 verschiedene Typen unterschieden werden, jedoch können auch atypische klinische Manifestationen auftreten. Aufgrund der verschiedenen klinischen Erscheinungsformen und eines häufig nicht genau unterscheidbaren histologischen Bildes, ist eine exakte Unterscheidung der verschiedenen Typen oftmals schwer oder sogar unmöglich. Wir berichten über einen Fall einer atypischen klinischen Manifestation einer Pigmentpurpura, der die Schwierigkeiten einer genauen klinischen Unterscheidung widerspiegelt.
Farbstofflaser‐Behandlung eines periungualen Granuloma pyogenicum
Authors: Tscharner Gion G. , Hunziker Thomas 
Published: January 2006

ZusammenfassungDie Behandlung eines Granuloma pyogenicum in Lokalisationen wie Gesicht oder Fingerkuppen gestaltet sich nicht immer einfach. Wir berichten über die erfolgreiche Therapie eines 1 cm messenden solchen Tumors periungual an einer Fingerkuppe mit dem Farbstofflaser.
Behandlung aktinischer Keratosen mit Birkenkorkextrakt: Eine Pilotstudie
Authors: Huyke Constance , Laszczyk Melanie , Scheffler Armin , Ernst Reinhard , Schempp Christoph M. 
Published: January 2006

Summary Background: Birch bark contains a variety of apoptosis‐inducing and anti‐inflammatory substances such as betulinic acid, betulin, oleanolic acid and lupeol. Therefore, birch bark extract may be effective in the treatment of actinic keratoses. To address this issue, a pilot study using a standardized birch bark ointment was performed. Methods: Twenty‐eight patients with actinic keratoses were enrolled in this prospective, non‐randomized pilot study. Fourteen patients were treated with birch bark ointment only; fourteen patients received a combination therapy with cryotherapy and birch bark ointment. Treatment response was assessed clinically after two months. Results: Clearing of more than 75 % of the lesions was seen in 79 % of the patients treated with birch bark ointment monotherapy. The response rate of the combined treatment modality was 93 %. Therapy with birch bark ointment was well tolerated. Conclusion: In this pilot study, a standardized birch bark extract was effective in the treatment of actinic keratoses. This therapy is easy to perform and it has no side effects. Birch bark ointment may be a new therapeutic option for actinic keratoses.
Neue Therapieansätze bei der Behandlung von Tumoren: Histondeacetylase‐, Methyltransferase‐ und Proteasominhibitoren
Authors: Becker Jürgen C. , Ugurel Selma , Bröcker Eva‐Bettina , Schrama David , Houben Roland 
Published: January 2006

ZusammenfassungNeue Erkenntnisse der Grundlagen und angewandten Forschung zu Fragen der Tumorentstehung und ‐progression bilden die Grundlage für moderne the‐rapeutische Entwicklungen. Gezielte Therapeutika greifen maßgeschneidert in molekulare Veränderungen der Onkogenese ein und ermöglichen so eine effektive und dabei wenig toxische Therapie von Tumoren einschließlich des Melanoms. Tumore basieren sowohl auf (zyto)genetischen als auch auf epige‐netischen Aberrationen. Das Schicksal einer Zelle beruht auf der feinen Balance von Expression und Repression von Genen. Die Beobachtung, dass in der Vielzahl von Tumoren dramatische Veränderungen der DNA‐Methylierung oder der Histonacetylierung vorliegen, führte zur Entwicklung und Charakterisie‐rung von Wirkstoffen, die diesen Umstand adressieren. Histondeacetylaseinhi‐bitoren oder Hemmstoffe der DNA‐Methylierung erlauben die Derepression von Tumorsuppressorgenen, während Proteasomeninhibitoren über eine verminderte Degradierung antitumoraler Proteine wirken. In der vorliegenden Übersicht sollen die theoretischen Grundlagen für diese neuen Therapie‐ansätze dargelegt werden.
Biology of the prolactin family in bovine placenta. I. Bovine placental lactogen: Expression, structure and proposed roles
Authors: TAKAHASHI Toru 
Published: January 2006

ABSTRACTBovine placenta produces an array of proteins that are structurally and functionally similar to pituitary prolactin. Bovine placental lactogen (bPL) is a glycoprotein hormone that has lactogenic and somatogenic properties. Purified bPL contains several kinds of isoforms that are created by alternative splicing and/or multiple glycosylation patterns. bPL can activate the prolactin (PRL) receptor‐mediated signaling pathway as well as PRL does. The bPL mRNA is transcribed in trophoblast binucleate cells, and synthesized bPL protein is stored in membrane‐bound secretory granules. The message encoding bPL is first detectable in trophoblast binucleate cells at approximately day 20 of gestation at, or shortly after, the appearance of binucleate cells in the trophoblast. Most binucleate cells are detected as expressed bPL in the placenta. Bovine PL may be the determinant in trophoblast differentiation. Although the biological activities of bPL have long been studied, the precise role of bPL is still largely unclear. This article reviews and discusses the biological roles of bPL, focusing on luteal function, fetal growth and pregnancy‐associated maternal adaptation, mammogenesis and lactogenesis, and placental angiogenesis. The precise biological function of bPL needs to be further evaluated.
Effects of forage‐to‐concentrate ratio in prepartum diet on the dry matter intake and milk yield of periparturient cows during hot weather
Authors: KAMIYA Yuko , KAMIYA Mitsuru , TANAKA Masahito 
Published: January 2006

ABSTRACTThe objective of this experiment was to study the effect of prepartum diets on dry matter intake (DMI) around parturition and on milk production in early lactation during a hot summer. Nine cows due to calve in July or August were assigned to two groups and fed either control (group C; four cows) or high‐concentrate (group H; five cows) diets to meet 110% of their energy requirements from 18 days before the expected calving date to parturition. The proportion of concentrate in the control diet was 35%, and that in the high‐concentrate diet was 45%. For 21 days after parturition, all cows were fed the same diets for lactation ad libitum. The DMI of cows in group H almost met their energy requirements. In group C, the DMI was decreased relative to group H and the concentration of plasma non‐esterified fatty acids was significantly higher (P < 0.05) before parturition. Therefore, the cows in group C were thought to be energy deficient before parturition. After parturition, there were no significant differences in DMI between the two groups. The milk yield of cows in group H tended to be higher than that of cows in group C at 21 days after parturition. Milk protein yield was significantly higher (P < 0.05) in group H 21 days after parturition relative to group C. There were no significant differences in milk composition between the two groups.
Dietary β‐alanine enhances brain, but not muscle, carnosine and anserine concentrations in broilers
Authors: TOMONAGA Shozo , KANEKO Kunio , KAJI Yuji , KIDO Yasuhiro , DENBOW Donald Michael , FURUSE Mitsuhiro 
Published: January 2006

ABSTRACTCarnosine (β‐alanyl‐L‐histidine) and its derivative anserine (β‐alanyl‐1‐methyl‐L‐histidine) are present in high concentrations in the muscle and brain of chickens. They are known as antioxidants and putative neurotransmitters in the brain. If administration of β‐alanine (β‐Ala), one of the constituents of carnosine, could increase the concentrations of these dipeptides in the brain and muscles, it could improve brain function and increase the commercial value of the meat in chickens. As an early step in investigating this hypothesis, in the present study, the effect of dietary β‐Ala on these dipeptide concentrations in the brain, Musculus pectoralis superficialis, Musculus pectoralis profundus and Musculus biceps femoris was investigated in broilers. Four‐week‐old broilers were given a commercial diet or diet containing 0.5, 1 or 2%β‐Ala for 4 weeks. At the end of the experiment, concentrations of both dipeptides were increased in the brain, while taurine concentration was decreased. In the muscles, concentrations of these dipeptides were unchanged. These results indicate that dietary β‐Ala might influence brain function, but is ineffective in increasing the concentrations of carnosine and anserine in the muscles of broilers.
Performance and welfare of broilers as affected by stocking density and zinc bacitracin supplementation
Authors: RAVINDRAN Velmurugu , THOMAS Donald V. , THOMAS David G. , MOREL Patrick C. H. 
Published: January 2006

ABSTRACTThe influence of stocking density (16, 20 and 24 birds/m2) and zinc bacitracin (0 or 100 mg/kg) on the performance, carcass characteristics and some indirect welfare indicators of broilers were examined in a 35‐day trial. The weight gain, feed intake, liveability and carcass characteristics of broilers grown at densities of 16, 20 and 24 birds per m2 were similar (P > 0.05). Over the whole trial period, however, feed per gain of birds at the highest density (24 birds/m2) was higher (P < 0.05) than those at the other two densities. Litter quality was poorer at high population densities, but there were no welfare implications as indicated by the lack of effect of density on gait scores and the incidence of hock and fat pad burns. Inclusion of zinc bacitracin improved weight gains and feed intake of broilers over the 35‐day trial period at all three stocking densities tested. Zinc bacitracin supplementation had no influence on the feed per gain of birds reared at densities of 16 and 20 birds/m2, but improvements were observed at a density of 24 birds/m2. The relative weights of lymphoid organs (spleen and bursa) were lowered (P < 0.05) with increasing density, suggesting a greater degree of stress on the birds. Zinc bacitracin supplementation had no influence on bursa weights of birds reared at densities of 16 and 20 birds/m2, but increased the bursa weights of birds reared at a density of 24 birds/m2. Overall, these data indicate that, with the removal of in‐feed antibiotics in the future, care should be taken when considering population densities of greater than 20 birds/m2.