bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro anti-inflammatory effect of Eucalyptus globulus and Thymus vulgaris: nitric oxide inhibition in J774A.1 murine macrophages
Authors: Vigo E , Cepeda A , Perez-Fernandez R , Gualillo O 
Published: February 2004

Abstract
It is well known that nitric oxide (NO) plays an important role in the pathogenesis of inflammatory diseases. Eucalyptus globulus Labill. and Thymus vulgaris L. have been used in traditional medicine in the treatment of bronchitis, asthma and other respiratory diseases. The present study focuses on the effects of these two extracts on NO production induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in the murine macrophage cell line J774A.1. In addition, cell viability, scavenging activity and inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. E. globulus and T. vulgaris extracts significantly inhibited the enhanced production of NO induced by LPS and IFN-γ in a dose-dependent manner. Treatment with these two extracts did not reduce cell viability at any dose used. Both plant extracts showed significant scavenging of NO radicals released by an NO donor, PAPANONOate. Results also show that pre-treatment with E. globulus and T. vulgaris extracts significantly inhibits iNOS mRNA expression. This study thus suggests that the inhibition of net NO production by these two extracts may be due to their NO scavenging activity and/or their inhibitory effects on iNOS gene expression.
Anti-tussive activity of benproperine enantiomers on citric-acid-induced cough in conscious guinea-pigs
Authors: Chen Siwei , Min Li , Li Weijing , Kong Weixi , Li Yan , Zhong Dafang 
Published: February 2004

Abstract
The anti-tussive effect of the R-(+)- and S-(-)-enantiomers of benproperine was evaluated and compared with that of the racemate on cough induced by 7.5% citric acid in conscious guineapigs. All the three compounds, intraperitoneally administered 1.5 h before the test, significantly inhibited citric-acid-induced cough. The ID50 values (effective doses for 50% inhibition) (with 95% confidence intervals) were 16.1 (9.1–28.4), 23.3 (11.2–48.6), 25.4 (11.7–55.1) mg kg−1 for the number of coughs in the 3 min of challenge, and 11.9 (5.3–26.6), 13.5 (5.6–32.4), 19.2 (12.8–28.9) mg kg−1 for the number of coughs in the 5 min immediately after the challenge, for (+)-benproperine, R-(+)-benproperine and S-(-)-benproperine, respectively. These findings suggest that the use of either enantiomer does not show any advantage over the racemate with regard to their anti-tussive effect.
The importance of gel properties for mucoadhesion measurements: a multivariate data analysis approach
Authors: Hägerström Helene , Bergström Christel A S , Edsman Katarina 
Published: February 2004

Abstract
In this study we used tensile strength measurements and a recently developed interpretation procedure to evaluate the mucoadhesive properties of a large set of gel preparations with diverse rheological properties. Multivariate data analysis in the form of principal component analysis (PCA) and partial least square projection to latent structures (PLS) was applied to extract useful information from the rather large quantities of data obtained. PCA showed that the selected series of gels was heterogeneous. Some groupings could be detected but none of the gels was identified as an outlier. By using PLS we investigated the relations between the rheological properties of a gel and the parameters defining the cohesiveness, as measured with the texture analyser used for the mucoadhesion measurements. The rheological properties proved to be important for the results of both the mucoadhesion and the cohesiveness measurements. Furthermore, by using PLS two different measurement configurations were evaluated and it was concluded that the combination of a relatively small volume of gel and two pieces of mucosa seems to be more appropriate than a large volume of gel in combination with one piece of mucosa.
Effects of gemfibrozil treatment on vascular reactivity of streptozotocin-diabetic rat aorta
Authors: Ozansoy G , Akin F B 
Published: February 2004

Abstract
The effects of gemfibrozil treatment on plasma lipids, lipid peroxides and vascular reactivity of aorta were investigated in diabetic rats. Rats were divided randomly into two groups: control and diabetic. Diabetes was induced by a single intraperitoneal injection of streptozotocin (45 mg kg−1). Twelve weeks after the induction of diabetes, some of the control and diabetic rats were started treatment with gemfibrozil (100 mg kg−1 daily; gavage) for 2 weeks. Blood glucose, plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol and thiobarbituric acid reactive substances (TBARS) levels were markedly increased and gemfibrozil treatment restored these parameters in diabetic rats. However high-density lipoprotein (HDL) cholesterol levels did not differ in all experimental groups. In diabetic rats, the endothelium-dependent relaxations to acetylcholine were decreased when compared with control rats. Gemfibrozil treatment restored the endothelium-dependent responses to acetylcholine in diabetic rats. The endothelium-independent relaxation responses to sodium nitroprusside were not altered in all groups. These findings suggest that gemfibrozil treatment has beneficial effects against cardiovascular and metabolic complications of diabetes via its hypolipidaemic and antioxidant properties.
Inhibiting cytokines of the interleukin-12 family: recent advances and novel challenges
Authors: Vandenbroeck Koen , Alloza Iraide , Gadina Massimo , Matthys Patrick 
Published: February 2004

Abstract
Interleukin-12 (IL-12) and the more recently discovered IL-23 and IL-27 constitute a unique family of structurally related, heterodimeric cytokines that regulate cell-mediated immune responses and T helper 1 (Th1)-type inflammatory reactions. Not surprisingly, the potentiality of treating conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA) through pharmacological interference with IL-12 pathways has received widespread attention. In this review we have examined over 50 substances with reported IL-12 inhibitory effects. We demonstrate that a majority of these belong to a limited number of major functional classes, each of which targets discrete events in the IL-12 biological pathway. Thus, most IL-12 inhibitory substances appear to work either through inhibition of transcription factor NF-κB activation, up-regulation of intracellular cAMP, blockage of posttranslational processing or interference with signal transduction pathways. In addition, cyclophilin-binding drugs, and generic inhibitors of nuclear histone deacetylases, and of ion channels, pumps and antiporters are emerging as potential leads to novel targets for interference with IL-12 production. Many inhibitors of NF-κB and of IL-12 signal transduction have been proven effective in limiting or preventing disease in experimental autoimmune encephalomyelitis (EAE) models of MS. The sharing of the p40 subunit, the IL-12Rβ1 and components of the signal transduction pathways between IL-12 and IL-23 raises the question as to whether the beneficial effects of various drugs previously ascribed to inhibition of IL-12 may, in fact, have been due to concurrent blockage of both cytokines, or of IL-23, rather than IL-12. Moreover, the homodimeric β2-form of IL-12, though originally considered to display only antagonistic effects, is now emerging as a pronounced agonist in a variety of inflammatory processes. Reassessment of IL-12 inhibitory compounds is therefore needed to scrutinize their effects on IL-12 αβ, β2 and IL-23 formation. This is likely to open exciting perspectives to the identification of drugs that target these cytokines either indiscriminately or selectively. The functional diversity of presently available inhibitors should facilitate an unprecedented flexibility in designing future trials for the treatment of IL-12- and IL-23-mediated disorders.
Acute nephrotoxicity of aristolochic acids in mice
Authors: Sato Noriko , Takahashi Daisuke , Tsuchiya Reiko , Mukoyama Takuya , Yamagata Shin-ichi , Satoh Nobunori , Ueda Shiro , Chen Shih-Ming , Ogawa Makoto , Yoshida Masaaki , Kondo Seizo 
Published: February 2004

Abstract
Aristolochic acids (AA), present in Aristolochia plants, are the toxin responsible for Chinese herbs nephropathy (CHN), a rapidly progressive tubulointerstitial nephritis (TIN). To clarify the mechanisms of the development of CHN, we tried to induce TIN in mice using AA. Three strains of inbred mice, BALB/c, C3H/He and C57BL/6, received 2.5 mg kg−1 of AA or AA sodium salt (AANa) daily by intraperitoneal or oral administration, 5 days a week for 2 weeks. Serum and renal tissue were obtained at sacrifice. Twelve-hour urine samples were individually collected in a metabolic cage at one-week intervals. In the AA-injected groups, severe tubular injury, with the appearance of acute tubular necrosis, and rare cell infiltration into the interstitium, were seen in BALB/c mice. C3H/He mice also developed TIN with prominent cell infiltration into the interstitium and interstitial fibrosis. In C57BL/6 mice, only mild and focal tubulointerstitial changes were seen. Serum creatinine and blood urea nitrogen increased in BALB/c and C3H/He mice. Immunofluorescent study revealed no deposition of immune components in kidneys. In the AANa-treated groups, TIN was also seen in all groups, but even more severe tubulointerstitial changes were induced by intraperitoneal injection. Further examination using purified AAI, AAII, AAIVa and aristolactam I (ALI) revealed that AAI induced strong nephrotoxicity in mice, and that AAII resulted in mild nephrotoxicity. However, AAIVa and ALI caused no nephrotoxicity in this experimental system. There are strain differences in mice in their susceptibility to AA nephropathy. AAI exerted the strongest nephrotoxic effect in mice.
Characterization of enzymes responsible for biotransformation of the new antileukotrienic drug quinlukast in rat liver microsomes and in primary cultures of rat hepatocytes
Authors: Szotáková Barbora , Skálová Lenka , Baliharová Vendula , Dvorščaková Martina , Štorkánová Lenka , Šišpera Luděk , Wsól Vladimír 
Published: February 2004

Abstract
The promising new drug quinlukast, 4-(4-(quinoline-2′-yl-methoxy)phenylsulphanyl)benzoic acid (VÚFB 19363), is under investigation for its anti-inflammatory and anti-asthmatic effects. The main metabolite of quinlukast identified in incubations of rat microsomal fraction, and in primary culture of rat hepatocytes, is quinlukast sulfoxide (M2). Also, several other metabolites of quinlukast were found: two dihydrodiol derivatives (M3, M5) and quinlukast sulfone (M4). This study was conducted to characterize the enzymes involved in quinlukast biotransformation in rat in-vitro. Primary cultures of rat hepatocytes were treated with inducers of different cytochrome P450s (CYPs) for 48 h. Quinlukast (100 μm) was incubated for 24 h in a primary culture of induced or control hepatocytes. The effects of CYP inhibitors, ketoconazole, methylpyrazole, metyrapone and α-naphthoflavone (2, 10, 50 μm), on quinlukast metabolism were tested in induced and control hepatocytes. Significant induction of M2 (6 times), M5 (twice) and M3 (by 50%) formation by dexamethasone and strong concentration-dependent inhibition by ketoconazole indicated that CYP3A participates in formation of these metabolites. CYP1A catalyses formation of metabolite M3 mainly, as β-naphthoflavone induced (10 times) production of M3 and a strong inhibitory effect of α-naphthoflavone on its formation was observed. A significant inhibitory effect of quinlukast (2, 10, 50 μm) on ethoxyresorufin, methoxyresorufin and benzyloxyresorufin O-dealkylase activity was observed as well.
Anti-ulcerogenic effect of chitin and chitosan on mucosal antioxidant defence system in HCl-ethanol-induced ulcer in rats
Authors: Anandan R , Nair P G Viswanathan , Mathew Suseela 
Published: February 2004

Abstract
The anti-ulcerogenic effect of chitin and chitosan against ulcer induced by HCl-ethanol in male Wistar rats was studied. Levels of acid output, pepsin, protein, lipid peroxides and reduced glutathione and the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were determined in the gastric mucosa of normal and experimental groups of rats. A significant increase in volume and acidity of the gastric juice was observed in the ulcer-induced group of rats. Peptic activity was significantly decreased as compared with that of normal controls. In the rats pre-treated with chitin and chitosan 2% along with feed, the volume and acid output and peptic activity of gastric mucosa were maintained at near normal levels. The level of lipid peroxidation was significantly higher in the ulcerated mucosa when compared with that of normal controls. This was paralleled by a decline in the level of reduced glutathione and in the activity of antioxidant enzymes like GPx, GST, CAT and SOD in the gastric mucosa of ulcer-induced rats. Also, the levels of mucosal proteins and glycoprotein components were significantly depleted in ulcerated mucosa. The pre-treatment with chitin and chitosan was found to exert a significant anti-ulcer effect by preventing all the HCl-ethanol-induced ulcerogenic effects in experimental rats.
Endothelin ETA receptor antagonist did not affect development of tolerance to glyceryl trinitrate in rat
Authors: Rai Aarati , Bhalla Shaifali , Gulati Anil , Gulati Anil 
Published: February 2004

Abstract
Glyceryl trinitrate (GTN), extensively used for the treatment of cardiovascular disorders, is associated with rapid development of tolerance. The exact mechanism responsible for tolerance development to GTN is still not known. Recently, it has been demonstrated that GTN tolerance is associated with increased expression of endothelin (ET). This study was carried out to determine the effect of ETA receptor antagonist, BMS182874, on the development of tolerance to GTN in urethane-anaesthetized rats. Diastolic blood pressure (DBP), systolic blood pressure (SBP) and heart rate (HR) were continuously recorded in vehicle- and BMS182874 (3 mg kg−1, i.v.)-treated rats. GTN was infused at the rate of 10 μg min−1, intravenously for 4 h. Tolerance to GTN was determined using challenge doses of GTN (10, 30 and 90 μg, i.v.). GTN produced a fall in DBP, SBP and an increase in HR. In vehicle-treated rats, the fall in SBP before induction of GTN tolerance was 28+2, 43+4 and 52+4 mmHg with 10, 30 and 90 μg GTN, respectively. However, following GTN infusion (10 μg min−1, i.v. for 4 h) a rapid development of tolerance was observed and the fall in SBP was 1+1, 9+4 and 15+4 mmHg with 10, 30 and 90 μg GTN, respectively. Similarly, in BMS182874-treated rats the fall in SBP in non-tolerant rats was 28+4, 42+4 and 48+5 mmHg with 10, 30 and 90 μg GTN, respectively. In BMS182874-treated rats following GTN infusion (10 μg min−1, i.v. for 4 h) a rapid development of tolerance was observed and the fall in SBP was 4+3, 10+2 and 13+4 mmHg with 10, 30 and 90 μg GTN, respectively. The decrease in DBP and SBP in vehicle- and BMS182874-treated GTN-tolerant rats was statistically similar. These results suggest that ETA receptor antagonist BMS182874 did not affect development of tolerance to GTN in rats.
Overexpression ofbroad: a new insight into its role in theDrosophilaprothoracic gland cells
Authors: Zhou Xiaofeng , Zhou Baohua , Truman James W. , Riddiford Lynn M. 
Published: February 2004

SUMMARYInsect molting is triggered by ecdysteroids, which are produced in the prothoracic glands (PG). The broad (br) gene is one of the`early genes' directly regulated by ecdysteroids. Ectopic expression of the BR-Z3 isoform in early second instar Drosophila larvae (L2) before the rise of the ecdysteroid titer prevented molting to the third instar, but the larvae subsequently formed L2 prepupae after prolonged feeding. When these larvae were fed on diet containing 20-hydroxyecdysone (20E), they formed pharate third instar larvae. The critical weight for normal L3 pupariation of w1118 larvae was found to be 0.8 mg and that for L2 pupariation was 0.45 mg. We also defined a threshold weight for metamorphosis of 0.3 mg, above which L2 larvae will metamorphose when provided with 20E. BR-Z3 apparently works through the PG cells of the ring gland but not the putative neurosecretory cells that drive ecdysone secretion, because ectopic expression of BR-Z3 specifically in the ring gland caused 53% of the larvae to become permanent first instar larvae. Driving other BR isoforms in the ring gland prevented larval molting or pupariation to varying degrees. These molting defects were rescued by feeding 20E. Overexpression of each of the BR isoforms caused degeneration of the PG cells but on different time courses,indicating that BR is a signal for the degeneration of the PG cells that normally occurs during the pupal–adult transition.
The anterior cardiac plexus: an intrinsic neurosecretory site within the stomatogastric nervous system of the crabCancer productus
Authors: Christie Andrew E. , Cain Shaun D. , Edwards John M. , Clason Todd A. , Cherny Elena , Lin Minhui , Manhas Amitoz S. , Sellereit Kirsten L. , Cowan Nicholas G. , Nold Kellen A. , Strassburg Hans-Peter , Graubard Katherine 
Published: February 2004

SUMMARYThe stomatogastric nervous system (STNS) of decapod crustaceans is modulated by both locally released and circulating substances. In some species, including chelate lobsters and freshwater crayfish, the release zones for hormones are located both intrinsically to and at some distance from the STNS. In other crustaceans, including Brachyuran crabs, the existence of extrinsic sites is well documented. Little, however, is known about the presence of intrinsic neuroendocrine structures in these animals. Putative intrinsic sites have been identified within the STNS of several crab species,though ultrastructural confirmation that these structures are in fact neuroendocrine in nature remains lacking. Using a combination of anatomical techniques, we demonstrate the existence of a pair of neurosecretory sites within the STNS of the crab Cancer productus. These structures, which we have named the anterior cardiac plexi (ACPs), are located on the anterior cardiac nerves (acns), which overlie the cardiac sac region of the foregut. Each ACP starts several hundred μm from the origin of the acn and extends distally for up to several mm. Transmission electron microscopy done on these structures shows that nerve terminals are present in the peripheral portion of each acn, just below a well defined epineurium. These terminals contain dense-core and, occasionally,electron-lucent vesicles. In many terminals, morphological correlates of hormone secretion are evident. Immunocytochemistry shows that the ACPs are immunopositive for FLRFamide-related peptide. All FLRFamide labeling in the ACPs originates from four axons, which descend to these sites through the superior oesophageal and stomatogastric nerves. Moreover, these FLRFamide-immunopositive axons are the sole source of innervation to the ACPs. Collectively, our results suggest that the STNS of C. productus is not only a potential target site for circulating hormones, but also serves as a neuroendocrine release center itself.
Does she smell like a queen? Chemoreception of a cuticular hydrocarbon signal in the ant Pachycondyla inversa
Authors: D'Ettorre Patrizia , Heinze Jürgen , Schulz Claudia , Francke Wittko , Ayasse Manfred 
Published: February 2004

SUMMARY
Primitive ant societies, with their relatively simple social structure,provide an opportunity to explore the evolution of chemical communication, in particular of mechanisms underlying within-colony discrimination. In the same colony, slight differences in individual odours can be the basis for discrimination between different castes, classes of age and social status. There is some evidence from correlative studies that such inter-individual variation is associated with differences in reproductive status, but direct proof that certain chemical compounds are detected and recognized by ants is still lacking. In the ponerine ant Pachycondyla inversa, fertile queens and, in orphaned colonies, dominant egg-laying workers are characterized by the predominance of a branched hydrocarbon,3,11-dimethylheptacosane (3,11-diMeC27) on the cuticle. Using electroanntennography and gas chromatography with electroantennographic detection, we show that the antennae of P. inversa workers react to this key compound. 3,11-diMeC27 is correlated with ovarian activity and, because it is detected, is likely to assume the role of a fertility signal reflecting the quality of the sender.
Mechanisms and significance of reduced activity and responsiveness in resting frog tadpoles
Authors: Lambert Thomas D. , Howard Jenny , Plant Andy , Soffe Steve , Roberts Alan 
Published: February 2004

SUMMARYHatchling Xenopus laevis tadpoles spend most of their time attached to objects or the water surface by mucus secreted by a gland on the head. While attached, swimming activity and responsiveness to swim-initiating stimuli are reduced over long periods of time. We have investigated the mechanisms and significance of this apparent long-term inhibition. In behavioural experiments we show, firstly, that innervation of the cement gland and GABAA-mediated inhibition are necessary for attachment to reduce responsiveness, and secondly, that denervation of the cement gland increases tadpole activity and increases their predation by damselfly nymphs(Zygoptera). To investigate the neuronal pathway from the cement gland to GABAA inhibition, we have devised an immobilized, inverted tadpole preparation where a weight attached to the mucus simulates the force as it hangs. Simulated attachment reduces responsiveness and spontaneous fictive swimming activity. We have recorded the activity and responses of trigeminal neurons innervating the cement gland. They are spontaneously active and simulating attachment results in a sustained increase in this activity. We propose that hanging from a mucus strand increases firing in cement gland afferents. This leads to tonic GABA inhibition that reduces tadpole activity and responses, and leads to fewer attacks by predators.
Isolation of a novel aquaglyceroporin from a marine teleost (Sparus auratus): function and tissue distribution
Authors: Santos C. R. A. , Estêvão M. D. , Fuentes J. , Cardoso J. C. R. , Fabra M. , Passos A. L. , Detmers F. J. , Deen P. M. T. , Cerdà J. , Power D. M. 
Published: February 2004

SUMMARYThe aquaporins (formerly called the major intrinsic protein family) are transmembrane channel proteins. The family includes the CHIP group, which are functionally characterised as water channels and the GLP group, which are specialised for glycerol transport. The present study reports the identification and characterisation of a novel GLP family member in a teleost fish, the sea bream Sparus auratus. A sea bream aquaporin (sbAQP)cDNA of 1047 bp and encoding a protein of 298 amino acids was isolated from a kidney cDNA library. Functional characterization of the sbAQP using a Xenopus oocyte assay revealed that the isolated cDNA stimulated osmotic water permeability in a mercury-sensitive manner and also stimulated urea and glycerol uptake. Northern blotting demonstrated that sbAQP was expressed at high levels in the posterior region of the gut, where two transcripts were identified (1.6 kb and 2 kb), and in kidney, where a single transcript was present (2 kb). In situ hybridisation studies with a sbAQP riboprobe revealed its presence in the lamina propria and smooth muscle layer of the posterior region of the gut and in epithelial cells of some kidney tubules. sbAQP was also present in putative chloride cells of the gill. Phylogenetic analysis of sbAQP, including putative GLP genes from Fugu rubripes, revealed that it did not group with any of the previously isolated vertebrate GLPs and instead formed a separate group, suggesting that it may be a novel GLP member.