bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo release and gene upregulation of brain prolactin in response to physiological stimuli
Authors: Torner Luz , Maloumby Rodriguez , Nava Gabriel , Aranda Jorge , Clapp Carmen , Neumann Inga D.
Published: April 2004

Although prolactin (PRL) actions and expression in the brain have been shown, dynamic changes in its intracerebral release and gene expression have still not been demonstrated. Using push‐pull perfusion, the in vivo release of PRL was monitored within the paraventricular nucleus (PVN) and medial preoptic area (MPOA) of virgin female, lactating and male rats in response to various stimuli. Perfusion with a depolarizing medium (56 mm K+) increased local release of PRL within both the PVN (P < 0.05) and MPOA (P < 0.05) of urethane‐anaesthetized rats, indicating release from excitable neuronal structures. The PRL in perfusates was verified by radioimmunoassay, Nb2 cell bioassays and western blot. Systemic osmotic stimulation (3 m NaCl i.p., 8 mL/kg b.w.) raised PRL concentration in plasma (P < 0.01) but not within the PVN, suggesting independent release from the pituitary and in distinct brain regions. Immobilization for 30 min increased PRL release within the PVN (P < 0.05) and the MPOA (P < 0.01) of virgin female and male (P < 0.05 each) rats and increased hypothalamic PRL mRNA expression (P = 0.008) after 30 and 90 min as revealed by real‐time polymerase chain reaction. This indicates a stress‐induced activation of both PRL release from and synthesis in hypothalamic neurons. Additionally, PRL was significantly released within, but not outside, the PVN (P < 0.01) and the MPOA (P < 0.05) of lactating rats during suckling and this was accompanied by a significant increase of PRL mRNA (P < 0.05) in the hypothalamus 60 min after suckling. This is the first demonstration of stimulus‐induced, locally restricted release and gene upregulation of PRL within the brain, emphasizing the involvement of this ‘novel’ neuropeptide in various brain functions.
Remodeling of reciprocal synapses associated with persistence of long‐term memory
Authors: Matsuoka Masato , Kaba Hideto , Moriya Keiko , Yoshida‐Matsuoka Junko , Costanzo Richard M. , Norita Masao , Ichikawa Masumi
Published: April 2004

We investigated a model of long‐term memory in which the female mouse establishes pheromonal memory of its partner at mating. We examined the reciprocal synapses of the accessory olfactory bulb and found that pheromonal memory was associated with morphological changes in excitatory synapses in the early phase of memory acquisition and by changes in inhibitory synapses in the late phases of memory persistence. After extinction of pheromonal memory, these morphological changes were no longer present. These findings suggest that the persistence of pheromonal memory is associated with continuous and dynamic changes in the morphological plasticity of reciprocal synapses in the accessory olfactory bulb.
Repairing the Breach of Trust in Corporate Governance
Authors: Child John , Rodrigues Suzana B.
Published: April 2004

The governance of companies, other than very small ones, operates through a double agency relationship. The first agency relationship is that between owners or stakeholders, on the one hand, and corporate management, on the other. The second agency relationship is that between corporate management and the employees of a firm, including middle managers, who execute its plans and policies. This second relationship has been largely ignored in discussions of corporate governance, yet its effectiveness is essential for achieving a firm's objectives. If employees have limited trust in their companies, the ability of corporate managers to have their intentions executed will be impaired. There is considerable evidence that such trust is today at a low ebb. This paper suggests policies that may help to repair employee trust and in so doing strengthen corporate governance. Its underlying theme is that greater attention to the trust that employees have in managers would help to achieve a long overdue realignment of corporate governance theory and policy.
Regional Disparities in Japanese Banking Performance
Authors: Miyakoshi Tatsuyoshi , Tsukuda Yoshihiko
Published: April 2004

This paper investigates whether technical inefficiency in production in the Japanese banking industry exhibits regional disparities by using the stochastic frontier model and data from the fiscal year 1999. First, we find evidence of regional disparities in technical inefficiency. Second, we find that regional disparities in technical inefficiency explain some of the disparities in regional income growth. Recent collapse of the regional banking systems in Japan was responsible for regional economic slumps. Third, we find that strong competition among banks and educational improvement by banks lead to improvements in banking performance. Finally, we find that the Merger Promotion Act currently in operation in Japan undermines recovery policies for regional banking.
Iraq, American Empire, And The War On Terrorism
Authors: Leaman George
Published: April 2004

Abstract: The U.S. government is trying to secure continuing American military and economic supremacy on a global scale over the long term. The U.S. invasion and occupation of Iraq is part of this imperial project, which is now being pursued under the mantle of the war on terrorism. This essay examines these developments in the context of U.S. military spending and foreign policy since the end of the cold war, and it argues that there is reason to be concerned about the continuing viability of democratic government in the United States.
“Us” and “Them”:
Authors: Norris Andrew
Published: April 2004

Abstract: In the Aristotelian tradition, politics is a matter of public deliberation over questions of justice and injustice. The Bush administration's response to the terrorist attacks of September 11, 2001, has been uniformly hostile to this notion, and it has instead promoted a jingoistic politics of self‐assertion by an America largely identified with the executive branch of its government. This is doubly disturbing, as the executive branch has sought to free itself from international law, multinational commitments, and domestic judicial regulation, even as it has sought to validate itself by demonizing its enemies. This essay draws out the disturbing echoes here of Carl Schmitt's work of the 1920s, in particular of Schmitt's conception of the sovereign as the ungrounded ground of the law and the political as the site of mortal conflict between friend and enemy. The essay argues that Schmitt's position in the twenties, for all of its evident problems, is superior to that of Bush, Wolfowitz, and Ashcroft in at least two senses: Schmitt condemns the idea of waging war for profit and recognizes that such wars will often be disguised as moral crusades waged against the “inhuman”; and he acknowledges that claiming to fight a war for humanity denies one's enemies their humanity, leaving them open to torture and even extermination.
The New Political Infamy and the Sacrilege of Feminism
Authors: Cornell Drucilla
Published: April 2004

Abstract: This essay is about women being crucial to the constitution of the state and the construction of the ideal of the nation. It argues that the role of actual women as reproducers of the nation and as iconic representations of mythological figures at the helm of nation building is bound up with a certain psychical fantasy of woman. It argues further that Women in Black and other political activist groups have developed embodied feminist politics that not only bring the feminine body into public view during wartime but also undermine the place of the good woman as the reproducer of the nation who mourns only for the lost soldiers of her people.
Reasons for Conflict: Political Implications of a Definition of Terrorism
Authors: Nuzzo Angelica
Published: April 2004

This essay analyzes the U.S. political situation before the 2003 invasion of Iraq and ties this conflict to the events of 9/11. The guiding thread of the discussion is the definition of “terrorism” that has led to George W. Bush's declared “war on terrorism.” By means of Hegel's dialectic logic, the essay exposes the problem offered by the category of causality involved in the definition of terrorism: Is terrorism the original “cause” of the war declared on it by the United States (as the Bush administration claims) or is terrorism rather the very “consequence” of that war?
Preemptive War, Americanism, and Anti‐Americanism
Authors: Losurdo Domenico
Published: April 2004

Abstract: The war against Iraq unleashed in March 2003 spawned an attempt to silence the protest movement by accusing it of anti‐Americanism. This essay argues that the theory according to which right‐wing anti‐Americanism and left‐wing anti‐Americanism coincide is a myth. A new issue appears now, a paradox that characterizes the United States, where democracy developed within the white community concomitantly with the enslavement of blacks and the deportation of American Indians. In the American “Herrenvolk democracy,” a line of demarcation between whites and people of color fosters the development of relations based on equality within the white community. Furthermore, U.S. history is marked by the fundamentalist tendency to transform the Judeo‐Christian tradition into a sort of national religion that consecrates the exceptionalism of the American people and the sacred mission with which they are entrusted (“Manifest Destiny”). Europe is unable thoroughly to comprehend the American mixture of religious and moral fervor, on the one hand, and overt pursuit of political, economic, and military world domination, on the other. But it is this mixture, or rather this explosive combination, this peculiar fundamentalism, that constitutes the greatest threat to world peace today.
On the So‐Called War on Terrorism
Authors: Rockmore Tom
Published: April 2004

Abstract: Since the terrorist attacks on the United States in September 2001, the country has embarked on a so‐called war on terrorism. This essay argues that so‐called war on terrorism has used the pretext of responding to terrorist attacks in the U.S. in September 2001 to wage wars in Afghanistan and Iraq that have objectives other than stamping out terrorism. It further argues that war requires a moral justification that cannot be provided for either the war in Afghanistan or the war in Iraq.
Terrorism and the New Forms of War
Authors: Margolis Joseph
Published: April 2004

Abstract: The March 2003 American preemptive strike on Iraq and related events pose entirely new conceptual questions about the notion of a valid war. A “war on terrorism” goes well beyond any usual version of the “just‐war” concept, which is itself notoriously difficult, if not impossible, to apply in current international circumstances. The implications of the emerging forms of war are examined and are found to bear in an unexpected way on justifying war, “just war,” and justice in distributional and related respects.
Differential sensitivities of pyrogenic chemokine fevers to CC chemokine receptor 5 antibodies
Authors: Tavares Eva , Miñano Francisco J.
Published: April 2004

Macrophage inflammatory protein (MIP)‐1β and RANTES (regulated on activation, normal T‐cells expressed and secreted) are members of the CC‐family of chemokines. Although these two peptides are structurally and functionally related to one another, each exhibits distinct features, which allows it to independently regulate specific aspects of the host inflammatory response. They evoked intense and functionally different febrile responses when applied directly on pyrogen‐sensitive cells located in the in the preoptic area of the anterior hypothalamus (POA). The present experiments were carried out to test the central role of CCR5, a functional receptor for MIP‐1β and RANTES, in the febrile responses induced by these chemokines when injected directly into the POA. The microinjection of an equimolecular dose (50 pg) of either MIP‐1β or RANTES into the POA induced a rapid onset; monophasic fever in rats that persisted for a long period. The microinjection of 2.0 μg specific neutralizing antibodies against CCR5 (anti‐CCR5) into the POA fails to affect the effects on body temperature induced by MIP‐1β. However, pretreatment with the same dose of anti‐CCR5 suppressed the febrile response induced by RANTES given at the same site. The microinjection of control IgG or anti‐CCR5 does not affect basal temperature, when administered alone at the same hypothalamic site. The present experiments show that hypothalamic CCR5 are functionally involved in the febrile response induced by RANTES, but not by MIP‐1β. They also suggest the existence of functionally different components in the presumptive primary locus of the thermoregulatory controller, in which both chemotactic cytokines, together other mediators, could play a relevant role in the complex process of fever pathogenesis.
Comparative effects of sildenafil, phentolamine, yohimbine and l‐arginine on the rabbit corpus cavernosum
Authors: Sharabi F. M. , Daabees T.T. , El‐Metwally M.A. , Senbel A.M.
Published: April 2004

Penile erection involves relaxation of smooth muscle of corpus cavernosum and associated arterioles. Sildenafil, a highly selective inhibitor of phosphodiesterase type 5, is effective in the treatment of erectile dysfunction. The aim of this study is to investigate the effect of sildenafil on smooth muscle of the rabbit corpus cavernosum (RCC) and to compare its effect with those of phentolamine, yohimbine and l‐arginine. The effects of sildenafil, phentolamine, yohimbine and l‐arginine were studied on the response of the RCC to electrical field stimulation (EFS) as well as on the phenylephrine (PE, 3 × 10−6 m)‐induced tone. EFS caused transient, frequency‐dependent relaxation of the RCC that was inhibited by the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine (3 × 10−5 m). Sildenafil (1 × 10−9–1 × 10−6 m) and phentolamine (1 × 10−9–1 × 10−6 m) enhanced the EFS‐induced relaxation in a concentration‐dependent manner with ED50 of 0.056 ± 0.004 and 0.572 ±0.035 μm at 8 Hz, respectively, yohimbine (3 × 10−7–3 × 10−5 m) and l‐arginine (3 × 10−6–3 × 10−4 m) did not show significant effects (ED50 at 8 Hz = 35.84 ±2.24 and 2.164 ± 0.174 μm, respectively). Sildenafil (1 × 10−9 and 1 × 10−8 m) potentiated the EFS‐induced relaxation caused by l‐arginine (3 × 10−5 m). Sildenafil, phentolamine, yohimbine and l‐arginine reduced the PE‐induced tone to different extents; the ED50 values were 0.81 ± 0.097, 0.49 ± 0.025 and 13.97 ± 1.10 μm, respectively. Maximum concentration of l‐arginine used failed to produce 50% relaxation (ED20 = 221.82 ± 15.71 μm). The muscle relaxant effects of different combinations of sildenafil and l‐arginine on PE‐induced tone did not differ significantly from the sum of the individual effects. The results demonstrate that sildenafil, when compared to other drugs used in penile erection dysfunction, shows the highest potency on the nitrergic transmission in the RCC. On the other hand, phentolamine was found to possess the highest potency in inducing relaxation of RCC proving that its action is independent on the stimulated neurogenic system. In addition, the combination of less effective doses of sildenafil and l‐arginine has a potential advantage on erectile functions. The importance of this combination remains to be solved clinically.
Tocolytic effects of intravenous nitroglycerin
Authors: Spirlet Marina de , Treluyer Jean‐Marc , Chevret Sylvie , Rey Elisabeth , Tournaire Michel , Cabrol Dominique , Pons Gérard
Published: April 2004

Currently available tocolytic agents have shown partial or transient efficacy on uterine contractions delaying delivery for 24 or 48 h without reduction in perinatal morbidity and mortality. These facts led us to study a new tocolytic compound. A double‐blind dose finding study of the nitroglycerin tocolytic effect during preterm labor was conducted using a continual reassessment method among six different doses (0.2–1.2 mg/h for 2 h) in pregnant women who were unresponsive, intolerant to salbutamol, or with a contraindication to this therapy. Twenty‐five pregnant women were included. The probability of success in stopping uterine contractions reached, for the maximal dose (1.2 mg/h), only a 54% rate (95% CI: 29–79%). Twelve patients complained of headaches and 16 experienced a decrease in arterial blood pressure suggesting that it would not be safe to increase the dose in order to obtain a higher success rate. The present study suggests that nitroglycerin is not as effective as expected in controlling uterine contractions during severe preterm labor in patients where β2 agonists cannot be used.
Effect of ajoene, a natural antitumor small molecule, on human 20S proteasome activity in vitro and in human leukemic HL60 cells
Authors: Xu Bo , Monsarrat Bernard , Gairin Jean Edouard , Girbal‐Neuhauser Elisabeth
Published: April 2004

The pharmacologic properties of ajoene, the major sulfur‐containing compound purified from garlic, and its possible role in the prevention and treatment of cancer has received increasing attention. Several studies demonstrated that induction of apoptosis and cell cycle blockade are typical biologic effects observed in tumor cells after proteasome inhibition. The proteasome is responsible for the degradation of a variety of intracellular proteins and plays a key role in the regulation of many cellular processes. The aim of the present work was therefore to explore the effects of ajoene on the proteasome activities. In vitro activities of 20S proteasome purified from human erythrocytes on fluorogenic peptide substrates specific for trypsin‐like, chymotrypsin‐like and peptidylglutamyl peptide hydrolyzing activities revealed that ajoene inhibited the trypsin‐like activity in a dose‐ and time‐dependent manner. Further, the ability of 20S proteasome to degrade the OVA51−71 peptide, a model proteasomal substrate, was partially but significantly inhibited by ajoene. In addition, when human leukemia cell line HL60 was treated with ajoene, both trypsin‐ and chymotrypsin‐like activities were affected, cells arrested in G2/M phase and total amount of cytosolic proteasome increased. All these data clearly indicate that ajoene may affect proteasome function and activity both in vitro and in the living cell. This is a novel aspect in the biologic profile of this garlic compound giving new insights into the understanding of the molecular mechanisms of its potential antitumor action.
The local anesthetic activity of Aconitum alkaloids can be explained by their structural properties: a QSAR analysis
Authors: Bello‐Ramírez Angélica M. , Nava‐Ocampo Alejandro A.
Published: April 2004

Alkaloids isolated from Aconitum roots exhibit anesthetic effects at peripheral nerves. We performed the present quantitative structure–activity relationship (QSAR) analysis in order to understand the mechanism of action as local anesthetics of 11 Aconitum alkaloids. The alkaloids with the highest anesthetic activity had an aroyl/aroyloxy group at R14 position while the weaker anesthetic alkaloids had the aroyloxy group at R4. The stable compounds exhibited a higher local anesthetic activity than the unstable compounds. In relation to the reactivity indexes of atoms on the aromatic ring, C2′ was more reactive while C3′ and C5′ were less reactive in the compounds with the highest anesthetic activity. Reactivity of N, C1′, C4′ and C6′ was similar between the two groups of alkaloids. The pKa was approximately 7.3 in both groups. The local anesthetic ED50 of alkaloids was significantly inversely related to molecular weight, core–core repulsion energy, steric energy and RI‐C2′, and directly related to electronic energy, total energy, RI‐C5′ and to the heat of formation. In conclusion, we identified a set of structural parameters that are related to the local anesthetic activity of Aconitum alkaloids. Our findings are useful to understand the mechanism of action of these alkaloids and to provide a rational for chemical manipulation of the compounds in order to obtain potent derivates with minor toxicity.
Nonsteroidal anti‐inflammatory drug‐induced liver injury: a case–control study in primary care
Authors: Lacroix I. , Lapeyre‐Mestre M. , Bagheri H. , Pathak A. , Montastruc J.L. ,   the Club de Reflexion des cabinets de Groupe de Gastro‐Enterologie (CREGG) and General Practitioner Networks
Published: April 2004

Several nonsteroidal anti‐inflammatory drugs (NSAIDs) have been withdrawn from the market because of hepatic adverse drug reactions (ADRs). Moreover, some cases of liver diseases have been reported in patients taking NSAIDs (arylcarboxylic NSAIDs, piroxicam, sulindac, nimesulide, etc.). Pharmacoepidemiological studies have shown a risk of hepatic ADRs with NSAIDs used in association with other hepatotoxic drugs. In contrast, other studies performed in hospitalized patients did not found any association. The aim of this study was to assess the hepatic risk associated with the use of NSAID in the setting of primary care. The study design was a case–control study where cases and controls were all recruited among patients seen in the context of medical community care. Eighty‐eight cases and 178 controls were included between January 1998 and December 2000. Cases used more drugs than controls in the 15 days before index day (2.9 ± 2.2 vs. 1.8 ± 1.8 different consumed drugs; P < 10−4). After adjustment, we found a significant association between liver injury and NSAID exposure in women [odds ratio (OR) = 6.49 (1.67–25.16)] but not in men [OR = 1.06 (0.36–3.12)]. A total of 22 cases were exposed to NSAIDs. Of them, seven patients were exposed to salicylates, five to diclofenac, four to ibuprofen, four to ketoprofen, two to niflumic acid, one to flurbiprofen and one to meloxicam (two patients were simultaneously exposed to two different NSAIDs: salicylate + niflumic acid and salicylate + diclofenac). These patients suffered from hepatocellular (53.3%), cholestatic (20%) or mixed (26.7%) injury. In 18 cases, liver enzymes returned to normal values after discontinuation of drug. No case had a fatal outcome. This study shows the existence of a significant association between liver disturbances and NSAID use in women.
Expression of cytochrome P450 4A mRNA in mouse lung: effect of clofibrate and interleukin‐1β
Authors: Bouquin Renaud Le , Lugnier Alain , Frossard Nelly , Pons Françoise
Published: April 2004

Cytochromes P450 4A (CYP4A) metabolize arachidonic acid into hydroxyeicosatetraenoic acids (HETEs) that exhibit potent actions on airway smooth muscle tone. In the lung, modifications in CYP4A expression and HETEs production could thus contribute to alterations in airway reactivity. We characterized expression of CYP4A in the lung of BALB/c mice, and studied its regulation by the CYP4A inducer, clofibrate and by the pro‐inflammatory and asthma‐associated cytokine, interleukin‐1β (IL‐1β). Messenger RNA (mRNA) expression of Cyp4a10, 4a12 and 4a14 was assessed in lung from control and clofibrate or IL‐1β‐treated mice using polymerase chain reaction after reverse transcription of total lung RNA. Cyp4a12 mRNA was the only Cyp4a mRNA detected in lung tissue from control mice, as well as mice treated with clofibrate or IL‐1β. In contrast, mRNA of all isoforms were found at significant levels in liver from control mice and at increased levels in liver from clofibrate‐treated animals. Lung levels of Cyp4a12 mRNA were enhanced by ninefold in mice treated with clofibrate and by fourfold in animals injected with IL‐1β. In conclusion, Cyp4a12, but not Cyp4a10 or Cyp4a14, is expressed in the lung of BALB/c mice, and may be upregulated by clofibrate or IL‐1β. Since IL‐1β has been largely associated with asthma, our data suggest that CYP4A expression could be altered in asthmatic conditions and may thus contribute to changes in airway reactivity.
Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes
Authors: Abi‐Gerges Najah , Philp Karen , Pollard Chris , Wakefield Ian , Hammond Tim G. , Valentin Jean‐Pierre
Published: April 2004

A number of non‐cardiovascular drugs have been withdrawn from clinical use due to unacceptable adverse cardiac side‐effects involving drug‐induced Torsades de Pointes (TdP) – a rare, life‐threatening polymorphic ventricular tachycardia associated with prolongation of the action potential duration of ventricular myocytes and, hence, prolongation of the QT interval, of the electrocardiogram (ECG), which measures the total time for activation of the ventricles and their recovery to the resting state. Research has suggested that women are more prone to develop TdP than men during administration of medicines that share the potential to prolong the QT interval, with 65–75% of drug‐induced TdP occurring in women.

Clinical and experimental studies show that female sex demonstrate differences in the electrocardiographic pattern of ventricular repolarization in human and other animal species and is associated with a longer rate‐corrected QT (QTc) interval at baseline than males. Reports of a similar propensity towards drug‐induced TdP in both premenopausal and postmenopausal women support factors in addition to those of female sex hormones eliciting sex‐based differences in ventricular repolarization. However, conflicting evidence suggests sex hormones may have a role in increasing the susceptibility of women or ultimately reducing the susceptibility of men to TdP.

Cyclical variations in hormone levels during the menstrual cycle have been associated with an increased and reduced risk of TdP. In contradiction to this finding, the male sex hormone is thought to be beneficial. Modulation of the ventricular repolarization by testosterone may explain why the QTc interval shortens at puberty, and might account for the tendency towards an age‐dependent reduction in the incidence of drug‐induced TdP in men. Mechanisms underlying these differences are not fully understood but a case for the involvement of gonadal steroids is obviously strong.

Therefore, further non‐clinical/clinical investigations ought to be a necessary step to elucidate any sex differences in cardiac repolarization characteristics, QT interval prolongation and susceptibility to cardiac arrhythmias. This may have implications for the development of the safest medicinal products and for the clinical management of cardiac arrhythmias.
The Two Schools of American Political Development
Authors: Glenn Brian J.
Published: April 2004

Political scientists working in the area of American political development (APD) focus on America's political history with the goal of explaining why the nation's often peculiar collection of institutions and policies grew the way they did. Two primary approaches or schools of inquiry shape much APD scholarship, though a great deal of very fine work falls outside of them: historical institutionalists study actors pursuing interests through a political arena bounded by institutions; and ideational scholars, in contrast, seek to understand how norms, narratives, and outlooks influence the framing of debates and their outcomes. Although there are exceptions, especially at the margins, each school is marked by a general outlook. Previous discussions of the two schools have focused on the place of culture and ideas in relation to institutions. I argue here that the two schools split along more fundamental lines, and suggest that the crucial distinction between them centers on the nature of causation and on an often-unstated understanding of what political development is. By mapping out the theoretical underpinnings of each, APD's methods can be introduced to researchers outside the subfield. And the question of how the two schools might be drawn together for even more powerful inquiry can be posed.
Cost‐effective screening method for antinuclear antibody detection
Authors: Anuradha V. , Chopra Arvind , Sturgess Allan S. , Edmonds John P.
Published: April 2004

Aim: To evaluate indirect immunoenzyme (IIE) technique, for detection of antinuclear antibodies (ANA) using serum and filter paper blood clots (FPBC) especially for screening.

Methods: Antinuclear antibody processing from FPBC (prepared by expressing blood drops by finger pricking) was standardized in a pilot study. Paired samples (serum and corresponding FPBC) from 224 individuals [142 patients of systemic rheumatic diseases, chiefly lupus and rheumatoid arthritis (RA) and 82 healthy controls (HC)] were tested by the standard immunofluorescence (IIF) and IIE (using light microscope); samples were coded, blinded and randomly processed as per the protocol. End‐point titres were determined for positive serum samples only. Standard reagents (Immunoconcepts Incorporation, US) and controls (CDC, Atlanta, US) were used. All patients were identified in a rheumatology referral practice in an Indian metropolis.

Results: The sensitivity of IIE and IIF for SLE, using serum and FPBC was ≈90%. The specificity of IIE and IIF for SLE, using serum and FPBC was in the range 66–73% and 58–63%, respectively. Good–perfect agreement (κ > 0.8) between the results was obtained by IIE and IIF for all groups except RA. Except the RA group, all other paired samples showed good concordance (72%) on testing for ANA patterns by both techniques.

Conclusions: Indirect immunoenzyme technique is a robust technique and should be considered a viable option to IIF at least in countries like India; its further use on FPBC is a socioeconomically appealing proposition for carrying out population studies on lupus and related uncommon connective tissue disorders.
Effect of methotrexate on pulmonary involvement in patients with rheumatoid arthritis
Authors: Gökhan Tas , Kürsat Özoran , Gülseren Ak , Sevinç Bostanoglu , Serpil Arikan , Bedriye Mermerci
Published: April 2004

Objective:  The aim of this study is to determine the effects of methotrexate (MTX) therapy on pulmonary involvement in patients with rheumatoid arthritis (RA).

Method:  Fifty‐five non‐smoking RA patients were included in the study. Routine laboratory investigations, pulmonary function tests (PFT), high resolution computed tomography (HRCT) and arterial blood gas analysis were performed in all of the patients. Randomly dividing the patients into two groups, the first group were given 7.5 mg/week MTX and the second group were given 250 mg/day chloroquine phosphate. At the end of the sixth month all the tests and the analysis were repeated and evaluated by using χ2 and Student's t‐test; P < 0.05 was considered statistically significant.

Results:  At the beginning of the study, HRCT examination revealed 92.7% pulmonary involvement in 55 RA patients. At the sixth month although the RA patients in the chloroquine group did not show any difference, RA patients in the MTX group displayed statistically significant increases in their pulmonary involvement (P < 0.05). Patients in the MTX group also displayed significant decreases at FEV1/FVC and significant increases at FEV1 in PFT and O2 saturation (P < 0.05, P < 0.05 and P < 0.01, respectively). In the chloroquine group we observed significant increases in FEV1 and vital capacity (P < 0.05).

Conclusion:  Although the MTX therapy increases the risk of pulmonary involvement in patients with RA, it also increases the ventilation which in turn increases the functional capacity of the patient. Considering the beneficial effect on the radiological progression of the disease, we think that MTX therapy should be taken into account as the first choice in the treatment of RA.
Normative bone mineral density values in Filipino women
Authors: Torralba Tito P. , Tan‐Ong Millicent Y. , Navarra Sandra V. , Dy Sarah H. , Saavedra Sue Celle T. , Bermudez Charito C. , Mercado‐asis Leilani , Llamado Lyndon Q. , Yu Julie L.
Published: April 2004

Objective:  To obtain reference values of bone mineral density (BMD) for Filipino women in order to make a population‐specific diagnosis of osteoporosis.

Method:  Sudy design: Cross‐sectional. Setting: Osteoporosis Unit, Joint and Bone Center, Section of Rheumatology and Clinical Immunology, Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines. Participants: 442 healthy Filipino women volunteers recruited from the outpatient department, Rheumatology and Clinical Immunology Clinic of the University of Santo Tomas Hospital and from within the University of Santo Tomas campus. Subjects with known underlying illness or conditions or intake of drugs that predispose to osteoporosis were excluded from the study. Intervention: Bone mineral density (BMD) measurements, expressed in grams per square centimenter of the lumbar spine, non‐dominant femur and non‐dominant forearm were done in 442 consecutive healthy Filipino women using the LUNAR DPX‐IQ machine.

Results:  Means and standard deviations of BMD measurements at each site were calculated using Kwikstat software Version 3.6, Release 7. Results were grouped in decades to serve as reference per decade.

Conclusion:  Bone mineral density measurements of these 442 healthy Filipino women may serve as an initial reference guide for the diagnosis of osteoporosis in Filipino women.
Comparative analysis of Behcet's disease in the APLAR region
Authors: Davatchi Fereydoun , Shahram Farhad , Kumar Ashok , Cheng Yew Kuang , Cheong Cheung Tak , Bendrups Andrea
Published: April 2004

Aims:  Behcet's disease (BD) was originally a disease of the Silk Road. Some authors think that BD from the Silk Road is different from those seen in other countries. The aim of this study was to analyze the clinical manifestations of BD in APLAR countries, where some of them are in the Silk Road (SR) and some others not (NSR).

Methods:  Data from Australia (NSR), Hong Kong (NSR), India (SR), Iran (SR), and Singapore (SR) were selected and analyzed under the same protocol. Prior published data from China (SR) Japan (SR) and Korea (SR) were included in the analysis.

Results:  The mean age at the onset of the disease was under 30 for all countries except Japan and Singapore. The male gender was more frequent except in Australia and Korea. Oral aphthosis was the most frequent manifestation (90–100%). Genital aphthosis was less frequent (57–82%). Skin manifestations were also frequent (61–87%). Ocular manifestations were reported from 21–69% of patients. The difference was mainly due to patients’ selection bias and the low number of patients in some reports. The same was true for joint (30–87%), gastrointestinal (6–38%), neurological (2.5–29%) and vascular manifestations (5–28%).

Conclusion:  Despite the percentage difference among some countries, the general pattern of the disease was the same, suggesting that the minor differences seen in different parts of the world were not enough to call the disease a syndrome, or to differentiate Behcet's disease of the Silk Road from those seen in Western countries.
Therapeutic advances in rheumatoid arthritis
Authors: Mok Chi Chiu , Mak Anselm
Published: April 2004

Over the past 15 years or so, there have been revolutionary changes in the treatment strategies of rheumatoid arthritis (RA). The traditional pyramidal approach has largely been replaced by the aggressive use of disease‐modifying antirheumatic drugs (DMARDs) in early disease. There has been continuing excitement with the introduction and use of the newer biological agents. While these novel agents have added to the armamentarium of RA treatment, rheumatologists are faced with the dilemma of drug cost and treatment effectiveness. In this article, the current concept of RA therapies and data regarding the newer biological response modifiers are discussed.
Successful usage of tacrolimus (FK506) in resistant/relapsed rheumatic diseases
Authors: Yoon Kam Hon
Published: April 2004

Aim:  This study reports the first successful usage of tacrolimus in various resistant or relapsed rheumatic diseases in Asian patients

Methods:  This is an open prospective study of the efficacy of tacrolimus for patients with various relapsed/resistant rheumatic diseases who were intolerant of or failed conventional therapy. Patients were enrolled in the study from the period November 2001 to September 2002.

Results:  A total of 20 patients were included in the study. Their disease conditions were as follows: SLE with relapsed lupus nephritis (six patients); SLE with antiphospholipid syndrome (APS) (two patients); rheumatoid arthritis (five patients); psoriatic arthritis (three patients); scleroderma (two patients); anti–Jo−1 syndrome (two patients). Improvement in their conditions were noted in all but one patient who was intolerant to tacrolimus.

Conclusions:  Tacrolimus (FK506) is a new armamentarium that can be added to the choice of immunosuppressive agents for rheumatologists, especially for those patients with severe or resistant diseases.
Factors affecting on the change of mood among Japanese RA patients
Authors: Sadamoto Kiyomi , Saito Eizo
Published: April 2004

Aim:  To evaluate factors affecting the change of mood among rheumatic arthritis (RA) patients.

Method:  Fifty‐five patients who satisfied ACR criteria for RA were given modified AIMS (Arthritis Impact Measurement Scales) test twice with a 1 year interval (2000, 2001). We also asked patients to write the average mood during the previous month. The questionnaire was performed using Lorish's Face Scale (FS). A correlation analysis was undertaken to examine the association between changes of FS (ΔFS) from the first year examination to the second year examination, and changes of disease activity (CRP, number of affected joints), and each questionnaire item.

Results:  Mean FS improved after 1 year. Patients of shorter therapy groups and younger patients showed larger improvement. Male patients showed larger improvement than female patients. ΔFS was strongly correlated with ΔCRP and Δnumber of affected joints. ΔFS were also strongly correlated with those of items which were related to activities of daily living (ADL). Especially, those related to the function of lower extremities showed stronger correlation with ΔFS than those related to functions of upper extremities. ΔFS among RA patients showed relatively weak correlation with Δpain factors as compare with ΔADL items.

Conclusion:  ΔADL is a larger influential factor on ΔFS than Δpain. Therefore, improvement of ΔADL seems to be one of the most important issues for the treatment of RA patients.
Photoactive benzophenone labelled peptide
Authors: Ali Marina , Amon Michael , Kurosaka Nozomu , Manolios Nicholas
Published: April 2004

Benzophenone and biotin labelled core peptide (CP) was prepared using benzophenone‐4‐maleimide. This photoactive peptide can be used in crosslinking experiments to give information of peptide–receptor association at molecular level.
Melatonin ameliorates chronic renal failure‐induced oxidative organ damage in rats
Authors: Şener Göksel , Paskaloǧlu Kübra , Toklu Hale , Kapucu Caner , Ayanoglu‐Dulger Gul , Kacmaz Ayhan , Sakarcan Abdullah
Published: April 2004

Abstract:  Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham‐operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05–0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05–0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH‐Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH‐Px activities of plasma demonstrate the role of oxidative mechanisms in CRF‐induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF‐induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit.
Age‐related changes in serum melatonin in mice: higher levels of combined melatonin and 6‐hydroxymelatonin sulfate in the cerebral cortex than serum, heart, liver and kidney tissues
Authors: Lahiri Debomoy K. , Ge Yuan‐Wen , Sharman Edward H. , Bondy Stephen C.
Published: April 2004

Abstract:  Age‐related changes in levels of melatonin and 6‐hydroxymelatonin sulfate and effects of dietary melatonin on their levels in different tissues were determined in mice. Levels of melatonin were highest in the serum followed by liver, kidney, cerebral cortex and heart as measured by a quantitative and sensitive enzyme‐labeled immunosorbent assay (ELISA). Serum melatonin levels decreased with age, and were reduced by 80% in 27‐month old mice relative to 12‐month old mice. Levels of 6‐hydroxymelatonin sulfate were measured independently in various tissues. Levels of the melatonin metabolite, 6‐hydroxymelatonin sulfate were significantly higher than free melatonin in all tissues tested. Levels of 6‐hydroxymelatonin sulfate were highest in the cerebral cortex followed by the serum, heart, kidney, and liver. In 12‐month old mice 6‐hydroxymelatonin sulfate concentration was approximately 1000‐fold greater than that of melatonin in the cerebral cortex, it was only 3‐fold greater than melatonin levels in the serum. Thus only 0.1% of total melatonin in the brain was present in the free and unconjugated form but the corresponding value for serum was 27.4%. The cerebral cortex had the highest levels of combined melatonin and 6‐hydroxymelatonin sulfate than other tissue tested in control mice. There was no significant change in 6‐hydroxymelatonin sulfate levels between young and old mice. There was also no age‐dependent change in levels of serotonin or cortisol in the serum samples. Dietary supplementation with melatonin resulted in a significant increase in levels of melatonin in the serum and all other tissue samples tested. Thus, any age‐related decline of tissue melatonin can be reversed by supplementation with dietary melatonin.
Dietary supplementation with melatonin reduces levels of amyloid beta‐peptides in the murine cerebral cortex
Authors: Lahiri Debomoy K. , Chen Demao , Ge Yuan‐Wen , Bondy Stephen C. , Sharman Edward H.
Published: April 2004

Abstract:  Melatonin levels decrease with aging in mice. Dietary supplementation with melatonin has recently been shown to result in a significant rise in levels of endogenous melatonin in the serum and all other tissue samples tested. Herein, the effects of dietary melatonin on brain levels of nitric oxide synthase, synaptic proteins and amyloid beta‐peptides (Aβ) were determined in mice. Melatonin supplementation did not significantly change cerebral cortical levels of nitric oxide synthase or synaptic proteins such as synaptophysin and SNAP‐25. Increased brain melatonin concentrations however, led to a significant reduction in levels of toxic cortical Aβ of both short and long forms which are involved in amyloid depositions and plaque formation in Alzheimer's diseases. Thus, melatonin supplementation may retard neurodegenerative changes associated with brain aging. Depletion of melatonin in the brain of aging mice may in part account for this adverse change.
Melatonin inhibits outward delayed rectifier potassium currents in hippocampal CA1 pyramidal neuron via intracellular indole‐related domains
Authors: Hou Shang‐Wei , Zheng Ping , Sun Feng‐Yan
Published: April 2004

Abstract:  In the present study, we investigated the effect of melatonin on the outward delayed rectifier potassium currents (IK) in CA1 pyramidal neurons of rat hippocampal slices using patch‐clamp technique in whole‐cell configuration. In a concentration‐dependent manner, melatonin caused a reduction of IK with a half‐maximal inhibitory concentration (IC50) of 3.75 mm. The inhibitory effect had rapid onset and was readily reversible. Melatonin shifted steady‐state inactivation of IK in hyperpolarizing direction but did not alter its steady‐state activation. Neither luzindole, an MT1/MT2 receptor antagonist, nor prazosin, an MT3 receptor antagonist, blocked melatonin‐induced current reduction. The results indicate that melatonin‐induced IK inhibition was not via activation of its own membrane receptors. 5‐Hydroxytryptamine (5‐HT), a melatonin precursor and an agonist of serotonin receptors, when it was given in pipette internal solution but not bath solution, produced a similar inhibitory effect to that of melatonin. Moreover, indole, a major component of melatonin, reversibly and dose dependently inhibited IK with an IC50 of 3.44 mm. Present results suggest that melatonin inhibits IK in hippocampal CA1 pyramidal neurons probably through its interaction with the intracellular indole‐related domains of potassium channels.
Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin
Authors: Gitto Eloisa , Reiter Russel J. , Amodio Aurelio , Romeo Carmelo , Cuzzocrea Elisabetta , Sabatino Giuseppe , Buonocore Giuseppe , Cordaro Vincenzo , Trimarchi Giuseppe , Barberi Ignazio
Published: April 2004

Abstract:  Improved survival from advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease (CLD). Recently, it was reported that inflammatory mediators such as interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α and IL‐8 are present in higher concentrations in lung lavage from babies who develop CLD. Previously, we found that melatonin reduced the rises in proinflammatory cytokines (IL‐6, IL‐8 and TNF‐α) and nitrite/nitrate levels in the serum of preterm newborns with respiratory distress syndrome (RDS). The values correlated with gestational age and iatrogenic trauma in the form of oxygen exposure and mechanical ventilation. Increased concentrations of proinflammatory cytokines may, therefore, be the most valuable early indicator of developing CLD and these measurements may assist in selecting infants for interventions such as melatonin treatment or more selective blockage of components of inflammation. In the current study, we extend the original observations and report results in which 120 newborns diagnosed with RDS were either treated with melatonin (60 children) or given placebo (60 children). The cytokine measures were consistent with the previously reported findings and showed that melatonin reduced these values and also lowered nitrite/nitrate levels in serum of newborns with respiratory distress. Furthermore, when nonmelatonin‐treated newborns who developed CLD (eight infants) were examined separately, they had levels of IL‐6, IL‐8, TNF‐α and nitrite/nitrate values much higher than those in children who did not develop CLD. Two of the nonmelatonin‐treated newborns died while no children who received melatonin died. Melatonin was well tolerated by the newborns.