bluuebunny/crossref_metadata_2025 huggingface dataset:
The detection and monitoring of early pregnancy in the vervet monkey (Cercopithecus aethiops) with the use of ultrasound and correlation with reproductive steroid hormones
Authors: Seier J.V. , Van Der Horst G. , De Kock M. , Chwalisz K.
Published: November 2003

Twenty early pregnancies were diagnosed and monitored in vervet monkeys by ultrasonography. Non‐gravid uteri became increasingly echogenic from cycle days 7 to 26. The first definite sign of pregnancy was a gestational cavity of 2 mm (±0.80) at 33.0 (±1.48) days menstrual age, which was also used to date all subsequent features. Earlier signs, such as an endometrial line swelling or endometrial ‘pregnancy’ ring, as reported for other non‐human primate species, could not be reliably and consistently used to diagnose pregnancy in vervet monkeys. A rapid increase of the gestational cavity size from days 37 to 49 corresponded closely to a rapid increase in plasma progesterone concentration from day 39 to 49. The first yolk sac was recognizable at 38.0 days (±3.10) and measured 3.3 mm (±0.40) in diameter. A heart beat could be detected at 45.5 (±1.73) days and the size of the first measurable embryo at 35 days was 2 mm. The dating of most features was within the range reported for other non‐human primate species.
Autoimmune hemolytic anemia (AIHA) in an infant rhesus macaque (Macaca mulatta)
Authors: Suzuki Juri , Gotoh Shunji , Miwa Norikatsu , Terao Keiji , Nakayama Hiroyuki
Published: November 2003

Autoimmune hemolytic anemia (AIHA) is a disorder associated with the destruction of red blood cells (RBCs) by autoantibodies. We report a rare case of AIHA in an infant rhesus macaque (Macaca mulatta) which received a continuous administration of four drugs, a dopamine agonist, dopamine receptor inhibitor, and two Γ‐aminobutyric acid receptor inhibitors into the brain during the course of neurophysiological experiments. The main clinical findings were severe anemia and splenomegaly. Hematological and serological examinations revealed the appearance of peripheral erythroblasts and autoantibodies against RBCs. Medical treatments, including washed RBC transfusion and corticosteroids, transiently improved the animal's anemia, but euthanasia was decided on 331 days after the start of the experiment. The pathological findings revealed severe anemia, splenomegaly, and extramedullary hematopoiesis in the liver and kidneys. These findings and the clinical course suggest that this anemia was a warm‐antibody type of AIHA induced by the administration of the drugs for the neurophysiological experiment.
Routine DNA analysis based on 12S rRNA gene sequencing as a tool in the management of captive primates
Authors: Van Der Kuyl Antoinette C. , Van Gennep David R.O. , Dekker John T. , Goudsmit Jaap
Published: November 2003

Automated DNA sequencing of a fragment of the relatively slowly evolving mitochondrial 12S rRNA gene was used to distinguish primate species, and the method was compared with species determination based upon classical taxonomy. DNA from blood from 53 monkeys housed at the Stichting AAP Shelter for Exotic Animals, all Old World monkeys, was amplified by polymerase chain reaction (PCR) with a primer set spanning approximately 390 nucleotides of the mitochondrial 12S rRNA gene. The products were directly sequenced and compared with our database of primate 12S sequences. Many individuals were found to harbor a 12S sequence identical to one of the reference sequences. For others, phylogenetic methods were used for species estimation, which was especially informative in Cercopithecus species.
Immunophenotyping of peripheral blood, ranges of serum chemistries and clinical hematology values of healthy chimpanzees (Pan troglodytes)
Authors: Stone G.A. , Johnson B.K. , Druilhet R. , Garza P.B. , Gibbs Jr C.J.
Published: November 2003

This paper presents clinical chemistry, hematology and immunophenotyping data from 102 chimpanzees over a 2‐year period. The groupings were: 3 years or less, 4–7 years, and 8+ years. These data are intended to augment formerly published information on these parameters and to serve as a concise reference guide for primate veterinarians and researchers for whom these data may be useful. This study has larger samplings than previously published data and more panel constituents by immunophenotyping.
Impact of lactation upon fertility in the New World primate capuchin monkey (Cebus apella)
Authors: Recabarren M.P. , Vergara M. , Martınez M.C. , Gordon K. , Serón‐Ferré M.
Published: November 2003

In the present paper, we have studied the impact of lactation upon fertility in the capuchin monkey, Cebus apella, under laboratory conditions. Nursing females (ten females, 12 postpartum periods) presented lactational amenorrhea (first menses at 159.2±9.0 vs 42.6±5.8 days postpartum in five non‐nursing females, seven postpartum periods). Plasma estradiol and progesterone concentrations during lactational amenorrhea were lower than those during the follicular phase of the menstrual cycle. Prolactin was higher than in non‐nursing females at 31–60 days postpartum. Interbirth interval, studied in three non‐nursing (four intervals) and six nursing females (eight intervals) lasted for 349.5±11.8 and 613.4±30.8 days, respectively. In non‐nursing females, early recovery of the menstrual cycle was followed by a residual infertility (mating but no pregnancy) lasting 152.8±7.9 days. In nursing females, recovery of the menstrual cycle was followed by an extended residual infertility of 301.5±22.7 days. Thus, in the capuchin monkey, nursing prolongs the interbirth interval by inducing lactational amenorrhea and extending the residual infertility period.
Radiation‐induced morphologic changes in the rhesus monkey (Macaca mulatta) brain
Authors: Price Roger E. , Langford Lauren A. , Jackson Edward F. , Stephens L. Clifton , Tinkey Peggy T. , Ang K. Kian
Published: November 2003

The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of another project were studied histopathologically 1–30 days after a single dose of 60Co‐irradiation. Histopathologically, inflammation and gliosis consistently occurred at specific time points but varied in severity between individuals. Multifocal hemorrhage, edema, and an acute neutrophilic inflammatory response were observed initially whereas perivascular accumulations of lymphocytes were observed in specimens at the end of the study. Microglia/macrophages were most prominent during the first week after irradiation, whereas astrocytes were reactive throughout the observation period. The early clinical manifestations of the central nervous system (CNS), because of brain irradiation in humans, correspond temporally with acute vascular responses, acute and subacute inflammatory cell responses, and subacute demyelination and reactive astrocytic and microglial responses observed in the rhesus monkey. Initial responses of the CNS to gamma‐irradiation may have potential implications for the development of radiation‐induced late injury of the CNS.
Cryopreservation of epididymal spermatozoa collected by needle biopsy from cynomolgus monkeys (Macaca fascicularis)
Authors: Feradis A.H. , Pawitri D. , Suatha I.K. , Amin M.R. , Yusuf T.L. , Sajuthi D. , Budiarsa I.N. , Hayes E.S.
Published: November 2003

We have examined the motility, morphology, and cryopreservation of epididymal spermatozoa collected by needle biopsy from cynomolgus monkeys (Macaca fascicularis). At collection, epididymal sperm (23×106±4×106 sperm/sample; 611×106±116×106 sperm/ml; n=18) were alive (79±2%), motile (67±2%), and exhibited intact membranes (65±2%). Sperm maintained at room temperature in handling medium exhibited decreased motility over time, but head‐to‐head agglutination was limited. Tris egg‐yolk extender containing 6% glycerol and dimethylsulfoxide (DMSO) did not significantly affect functional morphology, whereas extender containing propanediol significantly reduced motility, survival, and membrane integrity. Cryostorage reduced all measures of functional morphology independent of cryoprotectant. Post‐thaw motility was superior for glycerol and DMSO compared to propanediol. Variation in glycerol concentration (4, 6, and 8%) produced equivocal effects on sperm functional morphology post‐thaw. Needle biopsy may be a useful technique for laboratory and field‐based collection of spermatozoa from nonhuman primates.
Seasonal changes of humoral and cellular immune responses to Japanese cedar (Cryptomeria japonica) pollen allergens in Japanese monkeys (Macaca fuscata) with pollinosis
Authors: Sakaguchi Masahiro , Yamada Tomoko , Hirahara Kazuki , Shiraishi Akio , Saito Saburo , Miyazawa Hiroshi , Taniguchi Yoshifumi , Inouye Sakae , Nigi Hideo
Published: November 2003

The natural occurrence of Japanese cedar [Cryptomeria japonica (CJ)] pollinosis has been reported in Japanese monkeys (Macaca fuscata). The present study was designed to investigate seasonal changes in immunological reactions to CJ pollen allergens in monkeys with CJ pollinosis. Blood samples were collected from six monkeys with CJ pollinosis before and after CJ pollen season. Seasonal changes in specific IgE and IgG to major allergens (Cry j 1 and Cry j 2) were observed before and after CJ pollen season. The humoral responses decreased significantly before CJ pollen and increased after CJ pollen season. Similar seasonal changes in peripheral blood mononuclear cells proliferative responses to CJ allergens were observed before and after CJ pollen season. These humoral and cellular immune responses might serve as a biomarker for assessing new immunotherapies for monkeys with pollinosis.
Subcutaneous hemangiosarcomas in a rhesus macaque (Macaca mulatta)
Authors: Myers Jr. Daniel D. , Dysko Robert C. , Chrisp Clarence E. , Decoster John L.
Published: November 2003

Hemangiosarcoma is a malignant tumor of vascular endothelial cell origin. The occurrence of hemangiosarcoma in nonhuman primates has been rarely documented. An adult male rhesus monkey was reported having a firm subcutaneous swelling, approximately 4.5 cm in diameter, on the ventral midline of the abdomen. Fine‐needle aspiration, microbial culture, biopsy, radiographs, exploratory laparotomy, histopathology, immunohistochemistry, hematology, and serology were performed. A second subcutaneous mass approximately 4.5×4.0×2.7 cm developed on the ventral midline several weeks later. A fine‐needle aspirate of the first mass consisted of numerous erythrocytes with few polymorphonuclear cells and lymphocytes. Histopathology showed foci of spindle‐shaped cells surrounding the vascular spaces. Many spindle‐shaped cells had prominent nucleoli, and mitotic figures could occasionally be seen. Immunohistochemical staining of the masses for Factor VIII‐related antigen, an endothelial cell and tumor marker, yielded positive results. Both masses were consistent with hemangiosarcoma.
Effect of vaccination with recombinant modified vaccinia virus Ankara expressing structural and regulatory genes of SIVmacJ5 on the kinetics of SIV replication in cynomolgus monkeys
Authors: Negri Donatella R.M. , Baroncelli Silvia , Michelini Zuleika , Macchia Iole , Belli Roberto , Catone Stefania , Incitti Fabio , Ten Haaft Peter , Corrias Franco , Cranage Martin P. , Polyanskaya Natasha , Norley Stephen , Heeney Jonathan , Verani Paola , Titti Fausto
Published: November 2003

The efficacy of a multicomponent vaccination with modified vaccinia Ankara constructs (rMVA) expressing structural and regulatory genes of simian immunodeficiency virus (SIVmac251/32H/J5) was investigated in cynomolgus monkeys, following challenge with a pathogenic SIV. Vaccination with rMVA‐J5 performed at week 0, 12, and 24 induced a moderate proliferative response to whole SIV, a detectable humoral response to all but Nef SIV antigens, and failed to induce neutralizing antibodies. Two months after the last boost, the monkeys were challenged intravenously with 50 MID50 of SIVmac251. All control monkeys, previously inoculated with non‐recombinant MVA, were infected by week two and seroconverted by weeks four to eight. In contrast a sharp increase of both humoral and proliferative responses at two weeks post‐challenge was observed in vaccinated monkeys compared to control monkeys. Although all vaccinated monkeys were infected, vaccination with rMVA‐J5 appeared to partially control viral replication during the acute and late phase of infection as judged by cell‐ and plasma‐associated viral load.
Comparison of early plasma RNA loads in different macaque species and the impact of different routes of exposure on SIV/SHIV infection
Authors: Ten Haaft Peter , Almond Neil , Biberfeld Gunnel , Cafaro Aurelio , Cranage Martin , Ensoli Barbara , Hunsmann Gerhard , Polyanskaya Natasha , Stahl‐Hennig Christiane , Thortensson Rigmor , Titti Fausto , Heeney Jonathan
Published: November 2003

Various simian immunodeficiency virus (SIV)sm/mac and simian/human immunodeficiency virus (SHIV) strains are used in different macaque species to study AIDS pathogenesis, as well as to evaluate candidate vaccine and anti‐retroviral drugs efficacy. In this study we investigated the effect of route of infection, species of macaques and nature of virus stock on early plasma viral RNA load. We monitored the plasma RNA concentrations of 63 rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) infected with well‐characterised virus stocks administered either by oral, rectal, vaginal or intravenous (i.v.) routes. In SIVmac‐infected macaques, no significant difference in plasma RNA loads was observed between the rectal, oral and i.v. routes of infection. Cynomolgus macaques developed lower steady state SIV plasma RNA concentrations compared with rhesus macaques and no significant difference was observed between rectal and i.v. routes of infection. In SHIV89.6p‐infected macaques, no difference between species or between route of infection was observed with this particular chimeric virus.
Chronic immune stimulation accelerates SIV‐induced disease progression
Authors: Villinger François , Rowe Thomas , Parekh Bharat S. , Green Timothy A. , Mayne Ann E. , Grimm Bennett , McClure Harold M. , Lackner Andrew A. , Dailey Peter J. , Ansari Aftab A. , Folks Thomas M.
Published: November 2003

The contribution of chronic immune stimulation on the progression of lentivirus‐induced disease was evaluated in the SIVmac251 macaque model of AIDS. Following SIV inoculation, seroconversion and control of the acute viral replication phase, repeated immune stimulations with tetanus toxoid (TT), keyhole limpet hemocyanin (KLH) and allogeneic peripheral blood mononuclear cells (PBMC) were initiated in four monkeys. These animals showed a significant shortening of survival when compared with eight non‐immune‐stimulated control animals inoculated with the same route, dose and stock of SIVmac251 (median survival 9.5 months versus 17 months, P=0.010). In addition, when the comparison was extended to another 22 control animals of different origin but inoculated by the same route with similar doses and stocks of SIVmac251, the difference in survival was still significant (9.5 versus 18 months, P=0.003). This accelerated progression of symptomatic disease was not accompanied with significant increases in plasma viral loads, but suboptimal antibody responses to the immunizing antigens were noted, correlating with the length of survival. These findings may have implications for HIV‐infected humans suffering from chronic infectious diseases.
Spontaneous disc degeneration in the baboon model: Magnetic resonance imaging and histopathologic correlation
Authors: Craig Platenberg R. , B. Hubbard Gene , J. Ehler William , J. Hixson Clifford
Published: November 2003

Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20–26 kg, adult females 12–17 kg), long‐lived (30–45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multiplanar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P<0.001). The pathologic analysis demonstrated P values of <0.001 when comparing histopathology with age and MRI results. All severely degenerated discs seen by MRI were in baboons 14 years of age or older.
Reproductive maturation in a sample of captive male baboons
Authors: Muehlenbein Michael P. , Campbell Benjamin C. , Phillippi Kathrine M. , Murchison Mark A. , Richards Robert J. , Svec Frank , Myers Leann
Published: November 2003

Though baboons have been considered an appropriate non‐human primate model for studying human reproductive and endocrine development, the overall similarity of reproductive maturation between the two species is unclear. This paper examines the role of testicular and adrenal hormones for pubertal changes in a cross‐sectional sample of 21 captive male savanna baboons. Morphometric and hormonal indices demonstrate changes in size and gonadal function, but not adrenal function, during pubertal maturation among baboons. Results also indicate that gonadal, but not adrenal, androgens are related to morphometric variables. We conclude that savanna baboons do not make an appropriate evolutionary model of human pubertal maturation.
Taking Animals Seriously: William Wordsworth and the Claims of Ecological Romanticism
Authors: Mortensen Peter
Published: November 2003

Critics have long been aware that William Wordsworth borrowed from the German balladist Gottfried August Bürger in composing Lyrical Ballads (1798/1800). Wordsworth was both attracted and repulsed by Bürger's sensational and sensationally popular verse, yet the reason for this ambiguity has continued to baffle scholars. In this essay I turn to ecological criticism to cast a new light on the intertextual and cross‐cultural exchange between Bürger's “Der Wilde Jäger” and Wordsworth's “Hart‐Leap Well”. Wordsworth, I claim, was intrigued by Bürger's attempt to write a poem about hunting, yet in rewriting the German ballad Wordsworth also seeks to shift the emphasis somewhat, in such a way as to focus more explicitly on what he believed to be the main issue at stake: man's shockingly cruel treatment of animals. In thus reconceptualising Bürger's poem, Wordsworth inaugurates a new kind of Romantic nature poetry, which brings animals into the foreground and takes their suffering seriously. In the essay's final section, I defend Wordsworth's proto‐ecological vision against critics who believe that Wordsworth's love of nature caused him to lose interest in mankind. Far from leading necessarily to misanthropy or disillusionment, I argue, the vision propounded in ‘Hart‐Leap Well’ invites us to speculate how we can combine concern for the environment with a concern for our fellow men.
L'illusion levée. Regard journalistique et visualisation littéraire à partir de Balzac (XIXe siècle)
Authors: Lund Hans Peter
Published: November 2003

From Balzac and onward many writers of the nineteenth century published both journalism and literary fiction. This paper focuses, first, on the reexploitation and reorientation in Balzac of journalistic texts when refashioned in novels and short stories. Second, the paper compares the particular journalistic look with the literary strategies of visualization in texts by Nerval, Germain Nouveau, Villiers de l'Isle‐Adam and Zola. The intermingling of the look of the journalist with the authors' mimetic visualization underscores the importance of realism through the entire nineteenth century.
The Politics of Sacrifice: Hermann Broch's Critique of Fascism in Die Verzauberung
Authors: Mack Michael
Published: November 2003

This article is the first detailed discussion of the politics that determines the pseudo‐religion which characterizes the mass leader that Hermann Broch describes in Die Verzauberung. I shall analyze Broch's assessment of fascist politics as the politics of sacrifice. So far critics have neglected the fact that, like Ratti, the narrator of the novel sacrifices a woman (Barbara). I shall show that Broch's critique of both science and politics as sacrifice has to do with his understanding of Judaism as a religious and political way of life in which the idealisation of the sacrificial is tabooed.
»… bey einer guten Handlung böse Grundsätze zu argwohnen!« Empfindsame Diskurse bei Gellert, Sophie von La Roche und in Goethes Werther
Authors: Dörr Volker C.
Published: November 2003

Drei paradigmatische empfindsame Romane – Gellerts Das Leben der Schwedischen Gräfinn von G***, Sophie von La Roches Geschichte des Fräuleins von Sternheim und Goethes Werther– werden darauf hin befragt, was sich ihnen hinsichtlich der diskursiven Struktur der Empfindsamkeit ablesen läßt. Dabei werden, aufbauend auf Foucaults Bestimmungen, ein starker und ein schwacher Diskursbegriff unterschieden: Kriterium der Unterscheidung ist, ob eine ‘Formation’ sich selbst als Diskurs organisiert oder ob sie nur (nachträglich) als Diskurs beschrieben werden kann. Mit Hilfe dieser Differenz läßt sich eine signifikante, notwendige Entwicklung der Empfindsamkeit nachweisen, die die drei Romane auf unterschiedliche Weise reflektieren.
Theodor Herzl als reifer Dramatiker Gedanken um sein Schauspiel Das neue Ghetto
Authors: Albertsen Leif Ludwig
Published: November 2003

Bekannt ist Theodor Herzl (1860–1904) als zionistischer Agitator in den Jahren um 1900, literarisch mit seiner selbstbewußten Utopie Altneuland. Sein dramatisches Hauptwerk aus den 1890er Jahren Das neue Ghetto, das in Auseinandersetzung mit Arthur Schnitzler entstand, problematisiert demgegenüber jeden Weg ins Freie und galt bei seinem Erscheinen als politisch veraltet. Seine Bühneneffekte verdankt es Herzls früher großer Erfahrung in der Abfassung von Boulevardstücken. Diese wieder zu beachten lohnt freilich kaum, vielleicht auch nicht eine detailliertere Untersuchung der Facetten in seinem Verhältnis zum Freund und ärztlichen Helfer Max Nordau. Eher empfiehlt sich ein Blick auf Herzls vergessenes spätes Ideendrama Solon in Lydien (das Vf. anderweitig analysiert hat).
Experiment, Experience and Observation in Eighteenth‐Century Anthropology and Psychology – the Examples of Krüger's Experimentalseelenlehre and Moritz' Erfahrungsseelenkunde
Authors: Zelle Carsten
Published: November 2003

This article situates the role of Johann Gottlieb Krüger (1715–1759), one representative of Halle's “reasonable doctors”, as a link between Christian Wolff's empirical psychology and the anthropology of the late Enlightenment. Krüger's “Experimental Psychology” (1756) is analyzed, particularly the distinction drawn in his work between ‘observation’ and ‘experiment’ as experiential modi. Comparison between these modi and Karl Philipp Moritz' terminology of self‐observation and observation of the other shows that experimental and empirical psychology are closer than previous research has assumed.
The influence of diet consistence, drinking water and bedding on periodontal disease in Sprague‐Dawley rats
Authors: Björnsson Magnús Jón , Velschow Sten , Stoltze Kaj , Havemose‐Poulsen Anne , Schou Søren , Holmstrup Palle
Published: November 2003

Background:  Although rats have been extensively used in periodontal research, pre‐experimental periodontal inspection has not been given high priority in previous studies of experimental periodontal disease in rats. An inspection of 50 Sprague‐Dawley rats, which were to be used in a model of experimental periodontal disease, revealed signs of periodontal disease in a considerable proportion of the animals.

Objectives:  The objectives of the present study were to describe disease progression, identify factors responsible for induction of periodontal disease and test a method for breeding of healthy rats.

Methods and results:  A longitudinal study revealed that 33% of rats, bred under the same conditions, showed signs of periodontal disease during, or shortly after, eruption of the molars. Regular diet caused significantly more horizontal bone loss (P = 0.0001) and significantly less periodontal bone support (P < 0.0001) than the same kind of diet with a smaller grain size. Wood chip bedding in the rats' cages significantly reduced periodontal bone support (P < 0.0001) compared to a wire mesh floor and a simultaneous use of regular diet and bedding decreased it even further (P = 0.0023). Finally, by using finely milled diet, a wire mesh floor and tap water, instead of conventional breeding methods of regular diet, bedding and acidic water, it was possible to breed rats with minimal signs of periodontal disease.

Conclusions:  The results of the present study emphasize the need for pre‐ experimental examination of rats. They also show that diet and bedding conditions have the potential of seriously influencing outcomes of studies of periodontal disease in rats.
Effect of enamel matrix derivative on human periodontal fibroblasts: proliferation, morphology and root surface colonization. An in vitro study
Authors: Cattaneo V. , Rota C. , Silvestri M. , Piacentini C. , Forlino A. , Gallanti A. , Rasperini G. , Cetta G.
Published: November 2003

Background: 
Several clinical trials have shown the effectiveness of Emdogain® (EMD) in promoting tissue regeneration, even though the underlining biological mechanism is still poorly known.

Objectives:  The aim of the present study was to verify the effect of EMD on the proliferation of human periodontal ligament (PDL) fibroblasts and on their colonization and differentiation following contact with the root surface of extracted teeth in vitro.

Methods and results:  Fibroblasts from PDL were seeded on Petri dishes and cell growth was evaluated by cell counting in the presence and absence of EMD, after 1, 3 and 8 d of culture. A significant effect of EMD upon cellular proliferation at d 3 and 8 was detected. When PDL cells were grown for 12 d with EMD on etched human root surface, a change in cell morphology was observed. Scanning electron microscopy revealed that cells grown on root EMD‐treated surface present a body with a flattened surface closely adherent to the substrate and an outer smooth surface rounded in shape. From the flattened surface some thin and elongated cellular processes connecting with the substrate were also observable. PDL cells grown on EMD‐treated surface showed lack of alkaline phosphatase activity, as some authors noticed in cementoblasts in vitro.

Conclusions:  In conclusion, our data indicate that EMD enhances human PDL fibroblast proliferation. Furthermore, the cells in the presence of EMD show morphological changes that make them more similar to cementoblasts than to fibroblasts, suggesting a process of cellular differentiation that could play an important role in periodontal tissue repair.
Calprotectin release from human neutrophils is induced by Porphyromonas gingivalis lipopolysaccharide via the CD‐14–Toll‐like receptor–nuclear factor κB pathway
Authors: Kido Jun‐ichi , Kido Reiko , Suryono  , Kataoka Masatoshi , Fagerhol Magne K. , Nagata Toshihiko
Published: November 2003

Objectives:  Calprotectin is a cytosolic protein with antibacterial action in leukocytes and its level increases in some inflammatory diseases, including periodontal diseases, rheumatoid arthritis and ulcerative colitis. Recently, we found that the lipopolysaccharide of Porphyromonas gingivalis (P‐LPS) induced calprotectin release from human neutrophils. P‐LPS, a major virulence factor of periodontal pathogens, is known to induce the production and release of inflammatory cytokines through CD14, Toll‐like receptor (TLR) and nuclear factor κB (NF‐κB). In the present study, we investigated whether calprotectin release by P‐LPS is induced via the CD14–TLR–NF‐κB pathway and the cellular mechanism of calprotectin release in human neutrophils.

Material and methods:  Human neutrophils were isolated from the peripheral blood of healthy donors and pre‐incubated in medium containing antibodies against CD14, TLR2 and TLR4, or several inhibitors of NF‐κB, microtubules and microfilaments, and then incubated with P‐LPS. The calprotectin amount in the culture medium was determined using ELISA, and the nuclear extracts from cells were used for the examination of NF‐κB binding activity using electrophoretic mobility shift assays.

Results:  P‐LPS increased calprotectin release from neutrophils and its induction was inhibited by anti‐CD14 and anti‐TLR2 antibodies, but not by two anti‐TLR4 antibodies. NF‐κB inhibitors suppressed P‐LPS‐induced NF‐κB binding activity and calprotectin release. The inhibitors of microtubule and microfilament polymerization significantly decreased P‐LPS‐induced calprotectin release.

Conclusion:  These results suggest that calprotectin release is induced by P‐LPS via the CD14–TLR2–NF‐κB signal pathway in human neutrophils and may be dependent on microtubule and microfilament systems.
Stimulatory and entraining effect of melatonin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretion
Authors: Chu Yeh‐Shiu , Shieh Kun‐Ruey , Yuan Zung Fan , Pan Jenn‐Tser
Published: November 2003

The aims of the present study were to determine if melatonin exerts an effect on prolactin (PRL) secretion via the tuberoinfundibular dopaminergic (TIDA) neurons and if endogenous or exogenous melatonin has an entraining effect on the rhythmic changes of TIDA neuronal activity and PRL secretion. Melatonin given in the morning (10:00 h), dose‐ (0.01–1 mg/kg, ip) and time‐ (at 15 and 60 min, but not at 30 min) dependently stimulated TIDA neuronal activity in ovariectomized (OVX), estrogen‐treated rats as determined by 3,4‐dihydroxyphenylacetic acid (DOPAC) levels in the median eminence (ME). Serum PRL was concurrently inhibited by the injection. Melatonin administered in the afternoon (15:00 h) was even more effective in stimulating the lowered TIDA neuronal activity and inhibiting the increased PRL level than that given in the morning (10:00 h). S‐20098, a melatonin agonist was also effective in stimulating the TIDA neurons. In contrast, S‐20928, a putative melatonin antagonist, while it had no effect by itself, blocked the effect of S‐20098. Although S‐20928 failed to prevent melatonin's effect on ME DOPAC levels, six interspaced injections of S‐20928, from 18:00 to 01:30 h, significantly blocked the increase of ME DOPAC levels at 03:00 h, indicating that the endogenous melatonin may play a role. We further used rats that received daily injection of melatonin (1 mg/kg, ip) at 18:00 h for 10 days and found that the injection augmented basal TIDA neuronal activity at 11:00 h and blunted the afternoon PRL surge. In all, melatonin can have an inhibitory effect on PRL secretion by stimulating the TIDA neurons, and it may help to entrain the circadian rhythms of both TIDA neuronal activity and PRL secretion.
Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines
Authors: Kanishi Yosuke , Kobayashi Yoichi , Noda Seiko , Ishizuka Bunpei , Saito Kaoru
Published: November 2003

The effect of melatonin on endometrial cancer cell growth was investigated using two cell lines, SNG‐II and Ishikawa, which are different in their estrogen receptor status. A physiological concentration of melatonin (10−9 M) showed no growth
inhibitory effect on SNG‐II cells, which are estrogen receptor‐negative
at all cell densities and incubation times. In contrast, melatonin
significantly inhibited Ishikawa cells, which are estrogen
receptor‐positive at all cell densities tested after 96 hr incubation.
The greatest inhibition of Ishikawa cell growth was observed at
10−9 M melatonin, compared with other supra
(10−6, 10−8 M) or subphysiological
concentrations (10−10, 10−12 M). This
growth inhibitory effect of melatonin on Ishikawa cells was completely
blocked by 10−10 to 10−8 M concentrations of 17‐β estradiol administration. Pretreatment with luzindole, which is a selective melatonin receptor antagonist, prior to the addition of melatonin also blocked the inhibitory effect of melatonin on Ishikawa cells. This is the first study to demonstrate an anti‐proliferative effect of physiological melatonin on endometrial cancer cells in vitro. The present study revealed that melatonin also inhibits the growth of estrogen receptor positive endometrial cancer cells and that this effect of the pineal indole may be mediated by both steroid and melatonin receptors.
Melatonin‐induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo
Authors: Martín M. , Macías M. , Escames G. , Reiter R.J. , Agapito M.T. , Ortiz G.G. , Acuña‐Castroviejo D.
Published: November 2003

Melatonin displays antioxidant and free radical scavenger properties. Due to its ability with which it enters cells, these protective effects are manifested in all subcellular compartments. Recent studies suggest a role for melatonin in mitochondrial metabolism. To study the effects of melatonin on this organelle we used ruthenium red to induce mitochondrial damage and oxidative stress. The results show that melatonin (10 mg/kg i.p.) can increase the activity of the mitochondrial respiratory complexes I and IV after its administration in vivo in a time‐dependent manner; these changes correlate well with the half‐life of the indole in plasma. Melatonin administration also prevented the decrease in the activity of complexes I and IV due to ruthenium red (60 μg/kg i.p.) administration. At this dose, ruthenium red did not induce lipid peroxidation but it significantly reduced the activity of the antioxidative enzyme glutathione peroxidase, an effect also counteracted by melatonin. These results suggest that melatonin modulates mitochondrial respiratory activity, an effect that may account for some of the protective properties of the indoleamine. The mitochondria‐modulating role of melatonin may be of physiological significance since it seems that the indoleamine is concentrated into normal mitochondria. The data also support a pharmacological use of melatonin in drug‐induced mitochondrial damage in vivo.
Protective effect of melatonin against α‐naphthylisothiocyanate‐induced liver injury in rats
Authors: Ohta Yoshiji , Kongo Mutsumi , Sasaki Emi , Ishiguro Isao , Harada Nobuhiro
Published: November 2003

The protective effect of melatonin against α‐naphthylisothiocyanate (ANIT)‐induced liver injury with cholestasis was examined in rats injected once with the toxicant (75 mg/kg body weight (BW)). In rats injected with ANIT alone, liver injury with cholestasis did not occur 12 hr after the injection but appeared at 24 hr, judging from the serum levels of marker enzymes and components. When melatonin (10 or 100 mg/kg BW) was orally administered to the ANIT‐injected rats at 12 hr after the injection, the administered indoleamine dose‐dependently prevented the formation of liver injury with cholestasis. In rats injected with ANIT alone, serum lipid peroxide (LPO) concentration increased 24 hr after the injection, while liver LPO concentration increased 12 hr after the injection and further increased at 24 hr. Myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, in the liver of the ANIT‐injected rats increased 12 hr after the injection and further increased at 24 hr. The oral administration of melatonin (10 or 100 mg/kg BW) to the ANIT‐injected rats attenuated the increases in serum and liver LPO concentrations and liver MPO activity found at 24 hr after the injection in a dose‐dependent manner. These results indicate that orally administered melatonin at pharmacological doses protects against ANIT‐induced liver injury with cholestasis in rats, and suggest that this protective effect of melatonin could be due to its antioxidant action and its inhibitory action against neutrophil infiltration in the liver of ANIT‐injected rats.
Antisense experiments reveal molecular details on mechanisms of ICER suppressing cAMP‐inducible genes in rat pinealocytes
Authors: Pfeffer Martina , Maronde Erik , Korf Horst‐Werner , Stehle Jörg H
Published: November 2003

In the rat pineal gland neuronal signals determine the rhythmic synthesis of the hormone melatonin. Norepinephrine (NE) is the principal neurotransmitter that drives hormone synthesis by activating the cAMP signaling pathway. This activation depends on transcriptional and posttranscriptional regulatory mechanisms. The cAMP‐dependent transcriptional regulation of the rate‐limiting enzyme of melatonin synthesis, arylalkylamine‐N‐acetyltransferase (AA‐NAT) involves
the activating transcription factor (TF) CREB and the inhibitory TF ICER.
By silencing elements of this cAMP‐dependent neuroendocrine transduction
cascade we wished to gain further insight into the role of ICER in the
regulation of gene expression in rat pineal gland. Inhibition of specific
kinases in primary pinealocyte cultures showed that ICER induction
depends pivotally on the activation of cAMP‐dependent protein kinase II.
Eliminating ICER's impact by transfecting antisense constructs into pinealocytes revealed a predominant β‐adrenergic mechanism in regulating a cotransfected CRE‐inducible reporter gene and notably, also the endogenous AA‐NAT gene. Deciphering molecular details of the cAMP‐dependent gene expression in mammalian pinealocytes provides a basis for understanding the general architecture of this signaling pathway that serves adaptive processes ubiquitously in the organism.
Protective effect of melatonin against the 1‐methyl‐4‐phenylpyridinium‐induced inhibition of Complex I of the mitochondrial respiratory chain
Authors: Absi Elhadi , Ayala Antonio , Machado Alberto , Parrado Juan
Published: November 2003

In the present study, a novel property of melatonin is shown: a protective effect of melatonin on the respiratory chain in isolated rat liver mitochondria and in striatal synaptosomes treated with 1‐methyl‐4‐phenylpyridinium ion (MPP+). The cellular damage
caused by MPP+, a compound that produces a Parkinsonian‐like
syndrome in humans, is the result of the mitochondrial respiration
inhibition at the Complex I level and oxidative stress induction.
Treatment of mitochondria with MPP+ inhibits the respiration
rate. This effect was prevented by the inclusion of melatonin in the
incubation mixture. This preventive effect, which is not related to the
antioxidative properties of melatonin, seems to be due to the fact that
melatonin prevents MPP+ interaction with Complex I. These results suggest that melatonin may protect against the effect of several Parkinsonogenic compounds that are associated with progressive impairment of mitochondrial function and increased oxidative damage.
Preservation of the antioxidant status in chemically‐induced diabetes mellitus by melatonin
Authors: Sailaja Devi M.M. , Suresh Y. , Das U.N.
Published: November 2003

Oxidant stress is believed to be enhanced in patients with diabetes mellitus, which may lead to endothelial dysfunction and the development of atherosclerosis. In diabetes, hyperglycemia drives non‐enzymatic glycation and oxidation of proteins and lipids which enhances the formation of advanced glycation end products (AGEs), which may be involved in the pathogenesis of diabetic vascular disease. The macrovascular complications of diabetes seem to be due to enhanced cellular oxidant stress by the interaction of AGEs with their receptor. It would be worthwhile to devise methods to reduce this oxidant stress. In alloxan‐induced diabetic rats lipid peroxidation products were increased, while levels of nitric oxide glutathione peroxidase and superoxide dismutase were reduced. Melatonin restored these biochemical abnormalities to normalcy independent of hyperglycemia. This model can be used to study the role of oxidant stress in the development of macrovascular complications in diabetes mellitus.
Melatonin protects against stress‐induced gastric lesions by scavenging the hydroxyl radical
Authors: Bandyopadhyay Debashis , Biswas Kausik , Bandyopadhyay Uday , Reiter Russel J. , Banerjee Ranajit K.
Published: November 2003

The antiulcer effect of melatonin on gastric lesions caused by restraint‐cold stress or by indomethacin (IMN) was studied with the intent of determining the mechanism of action of the indole. Melatonin dose‐dependently prevents both stress and IMN‐induced gastric damage with around 90% inhibition at a dose of 60 mg per kg BW. When compared with already‐marketed antiulcer drugs, such as ranitidine and omeprazole, melatonin was found to be more effective than ranitidine but less effective than omeprazole in preventing stress ulcer. When compared with other antioxidants, melatonin was more potent than glutathione and essentially equipotent to α‐tocopherol in blocking stress‐induced ulcer. As stress‐induced gastric lesions are mainly caused by oxidative damage due to hydroxyl radicals (OH), the effect of melatonin in scavenging the OH generated during stress conditions, as well as in an in vitro model system, was studied. The results indicate that melatonin at the dose of 60 mg per kg BW caused an 88% reduction of endogenous OH during stress. Melatonin was also highly effective in scavenging OH generated in vitro by a Cu2+‐ascorbate system. In this case, melatonin at 100 μM reduced OH by 80%. Melatonin was also found to be a more potent radical scavenger than benzoate, a known OH scavenger. The results indicate that melatonin prevents stress‐induced gastric lesions by scavenging the endogenous OH. As it also protects against IMN‐induced gastric damage, it probably also offers gastroprotection by maintaining endogenous prostaglandin levels.
Attenuation by melatonin of human umbilical arterial vasoconstriction induced by lysophosphatidylcholine
Authors: Okatani Yuji , Wakatsuki Akihiko , Watanabe Kazushi , Fukaya Takao
Published: November 2003

We evaluated the antioxidant property of melatonin as related to the vasospastic effect of lysophosphatidylcholine (LPC), a component of oxidized lipoprotein, on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between 37 and 39 wk of gestation. Changes in maximal tension induced by KCl were measured in arterial sections having intact endothelium. Sections were treated with LPC alone (15 or 30 μM), or were pretreated either with a hydrogen peroxide (H2O2) scavenger (catalase, 1,200 U/mL), a hydroxyl
radical scavenger (mannitol, 30 mM), a nitric oxide (NO) synthesis
inhibitor (L‐NG‐monomethyl arginine, LNMA,
2×10−4 M) or melatonin (1 or 10 μM). The effect of LPC (30 μM) on the vasorelaxation induced by 5‐hydroxytryptamine (5‐HT) was also determined, with or without melatonin pretreatment (10 μM). LPC potentiated vascular tension in a concentration‐dependent manner. Pretreatment with LNMA significantly suppressed this vasospastic effect of LPC. Pretreatment with catalase or mannitol significantly reduced the vasospastic effect of LPC. Melatonin significantly lessened the vasospastic effect of LPC in a concentration‐dependent manner. Pretreatment with LPC significantly inhibited the relaxation induced by 5‐HT. Treatment with melatonin prior to LPC exposure significantly restored the relaxation induced by 5‐HT. Results suggest that LPC potentiates vascular tension in human umbilical artery, perhaps by suppressing the endothelial synthesis of NO. Melatonin significantly suppressed the vasospastic effect of LPC. This agent probably scavenges the hydroxyl radicals arising from LPC.
Seeking Quality in Training Public Financial Managers: The Place for Certification
Authors: Brintnall Michael
Published: November 2003

The search for quality in public management has been provoked in recent years, mainly by the decline in the public's trust of government and by the growing interest in the development of performance measures. A general assumption that certification of public financial managers will enhance the quality of public management and will thus return public trust in government and the respect for its servants underlies the issues discussed in this article. It focuses on the endeavors to link certification and credentialing of financial managers to broader alternative strategies for assuring quality. The strengths and weaknesses of three major strategies and the available resources for their implementation are discussed: (1) promoting quality within public management education and training; (2) promoting quality within the environment where managers work; and (3) promoting quality of skills held by individual managers themselves.
Should There Be an Accreditation Program for Finance and Budget Offices?
Authors: Hildreth W. Bartley
Published: November 2003

Professionals in public finance and budgeting face a multi‐faceted credential environment, including current programs that accredit academic degrees, that bestow credentials on individuals, and that award work products meeting national standards. This article addresses a proposal to accredit the organizational unit with responsibility for budgeting and finance functions.
The Monster that Ate the United States Senate
Authors: Dauster Bill
Published: November 2003

Under this allegorical title the article addresses the lawmaking process that has led to the acceptance of three major laws: the 1996 welfare law, the 1997 tax law, and the 1997 balanced budget law. The article presents the author's critical views regarding the budget reconciliation process that underlies the acceptance of these laws.
Budgeting for Federal Capital
Authors: Posner Paul L. , Lewis Trina V. , Laufe Hannah
Published: November 2003

This article examines the issues involved in federal investment budgeting and planning for the acquisition of federally‐owned assets. It describes the unique role of the federal government and examines the different issues and reforms prompted by differing types of capital and investment sponsored at the federal level. It suggests that meaningful changes can be instituted in our budgeting practices that can make a difference for our budgetary choices without adopting a full‐scale capital budget. It also presents a framework for improving federal agency capital decision making based on a study of practices used by leading state and local and private sector organizations. The article is based on testimony delivered before the President's Commission to Study Capital Budgeting.
The Fables and Foibles of Federal Capital Budgeting
Authors: Gordon Cameron
Published: November 2003

This article critically evaluates the notions behind proposals to institute capital budgeting at the federal level. Four critical assumptions are found to be behind the contention that capital budgeting will improve federal investment policies: (1) an agreed‐upon and accepted definition of a capital budget exists; (2) a capital budget “adds value” by improving the quality of information; (3) better information leads to better decisions; (4) better decisions lead to better actions. Each of these assumptions is evaluated using examples drawn from various levels of government and from the private sector. The general finding is that if these assumptions hold, then it is reasonable to expect that capital budgeting will lead to better programmatic decisions. Unfortunately, one or more of these assumptions usually does not hold and for this reason the case for federal capital budgeting is not very strong