bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of the olfactory amygdala prevents the endocrine response to male odour in anoestrus ewes
Authors: Gelez H. , Archer E. , Chesneau D. , Magallon T. , Fabre‐Nys C. 
Published: April 2004

AbstractOur aim was to study the role of the olfactory amygdala (medial and cortical nuclei) and the ventromedial nucleus of the hypothalamus (VMN) in the ability of the male odour or live males to induce a release of luteinizing hormone in anoestrus ewes. To achieve this, we temporarily blocked the activity of these structures by localized retrodialysis administration of the anaesthetic lidocaine. The effect of ram odour on the secretion of luteinizing hormone was completely blocked by inactivation of the cortical nucleus of the amygdala. In contrast, inactivation of part of the accessory olfactory system (the medial nucleus of the amygdala or the VMN) had no effect. In the presence of the male, lidocaine never impaired the endocrine response of the ewes. These results show that modulation of reproduction by the sexual partner even through pheromonal cues does not occur via the direct circuit of the accessory system. On the contrary, the cortical nucleus of the amygdala is absolutely necessary for the treatment of and/or the response to the male olfactory signal but this structure can be bypassed when other sensory cues are available.
Unusual cone and rod properties in subterranean African mole‐rats (Rodentia, Bathyergidae)
Authors: Peichl Leo , Němec Pavel , Burda Hynek 
Published: April 2004

AbstractWe have determined the presence of spectral cone types, and the population densities of cones and rods, in subterranean mole‐rats of the rodent family Bathyergidae, for which light and vision seems of little importance. Most mammals have two spectral cone types, a majority of middle‐ to long‐wave‐sensitive (L‐) cones, and a minority of short‐wave‐sensitive (S‐)cones. We were interested to see whether the subterranean bathyergids show the same pattern. In three species, Ansell's mole‐ratCryptomys anselli, the giant mole‐ratCryptomys mechowiand the naked mole‐ratHeterocephalus glaber, spectral cone types and rods were assessed immunocytochemically with opsin‐specific antibodies. All three species had rod‐dominated retinae but possessed significant cone populations. A quantitative assessment inC. anselliandC. mechowirevealed surprisingly low photoreceptor densities of 100 000–150 000/mm2, and high cone proportions, ≈ 10% (8000–15 000/mm2). In all three species, the vast majority of the cones were strongly S‐opsin‐immunoreactive; L‐opsin immunoreactivity was much fainter. InC. anselli, ≈ 20% of the cones showed exclusive S‐opsin label, ≈ 10% exclusive L‐opsin label and ≈ 70% strong S‐opsin and faint L‐opsin double label (potential dual‐pigment cones). This is the first observation in any mammal of an S‐opsin dominance and low levels of L‐opsin across the entire retina. It contrasts starkly with the situation in the muroid blind mole‐ratSpalax ehrenbergi,which has been reported to possess L‐opsin but no S‐opsin. Evidently, within rodents an adaptation to subterranean life is compatible with very different spectral cone properties.
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

AbstractAlthough 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

AbstractWe 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.
Reasons for Conflict: Political Implications of a Definition of Terrorism
Authors: Nuzzo Angelica 
Published: April 2004

Abstract: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?
Differential sensitivities of pyrogenic chemokine fevers to CC chemokine receptor 5 antibodies
Authors: Tavares Eva , Miñano Francisco J. 
Published: April 2004

AbstractMacrophage 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

AbstractPenile 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

AbstractCurrently 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

AbstractThe 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

AbstractAlkaloids 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

AbstractSeveral 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

AbstractCytochromes 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

AbstractA 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.
Cost‐effective screening method for antinuclear antibody detection
Authors: Anuradha V. , Chopra Arvind , Sturgess Allan S. , Edmonds John P. 
Published: April 2004

AbstractAim: 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.