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61.
62.
Pierangelo Geppetti Riccardo Patacchini Roberto Cecconi Manuela Tramontana Stefania Meini Andrea Romania Marco Nardi Carlo Alberto Maggi 《Naunyn-Schmiedeberg's archives of pharmacology》1990,341(4):301-307
Summary Capsaicin-sensitive sensory neurons of the rabbit iris, by releasing tachykinins, exert a major role in the control of pupil motility in response to various noxious stimuli. However, the contribution of sensory innervation to the regulation of iris smooth muscle tone in other mammals species is not known. We have studied the effects produced by electrical field stimulation, capsaicin, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and bradykinin in the isolated iris sphincter muscle of the pig.Capsaicin (10 M): a) contracted the isolated sphincter muscle and; b) released immunoreactivity for substance P (SP-LI) and CGRP (CGRP-LI) from this preparation. These two effects were no longer observed at the second exposure to the drug. Electrical field stimulation (10 Hz, 60 V, 0.5 ms for 5 s) produced a biphasic contractile response. The rapid component was inhibited by atropine (1 M), while the delayed response was blocked by previous exposure to capsaicin (10 M).Substance P and neurokinin A consistently produced contraction of the pig iris sphincter muscle, substance P being more potent than neurokinin A. CGRP induced a contractile response in more than 50% of the preparations. The tachykinin antagonist [D-Argl, D-Trp7,9, Leu11-substance P (3 M) blocked: a) the effect of substance P (1 nM); b) the delayed response to electrical field stimulation and; c) reduced by more than 50% response to capsaicin. Bradykinin (10 M) failed to release either SP-LI or CGRP-LI. The contractile response evoked by bradykinin was unaffected by in vitro pretreatment with capsaicin (10 M).The existence in the pig iris of capsaicin-sensitive sensory fibres releasing neuropeptides and thus regulating sphincter muscle tone is proposed.
Send offprint requests to Dr. P. Geppetti at the above address 相似文献
63.
Jenny Englert Lena Witzdam Dominik Söder Manuela Garay-Sarmiento Anton Joseph Anna M. Wagner Cesar Rodriguez-Emmenegger 《Macromolecular chemistry and physics.》2023,224(24):2300306
The immobilization of vesicles has been conceptualized as a method to functionalize biointerfaces. However, the preservation of their integrity post immobilization remains a considerable challenge. Interfacial interactions can cause vesicle rupture upon close surface contact and non-specific protein adsorption impairing surface functions. To date, immobilization of vesicles has relied solely on either entrapment or prior modification of vesicles, both of which require laborious preparation and limit their applications. This work develops a bioinspired strategy to pin vesicles without prior modification while preserving their intact shape. This work introduces antifouling diblock copolymers and ultrathin surface-attached hydrogels containing a brush-like interface consisting of a bottle brush copolymer of N-(2-hydroxypropyl) methacrylamide (HPMA) and N-(3-methacrylamidopropyl)-N,N-dimethyldodecan-1-aminiumiodide (C12+). The presence of positive charges generates an attractive force that pulls vesicles toward the surface. At the surface, the amphiphilic properties of the combs facilitate their insertion into the membrane, mimicking the harpooning mechanism observed in antimicrobial peptides. Importantly, the antifouling poly(HPMA) backdrop serves to safeguard the vesicles by preventing deformation and breakage. Using a combination of thermodynamic analysis, surface plasmon resonance, and confocal laser scanning microscopy, this work demonstrates the efficiency of this biomimetic system to capture vesicles while maintaining an antifouling interface necessary for bioapplications. 相似文献
64.
Modulation of electrically evoked [3H]-noradrenaline release from cultured chick sympathetic neurons
Clemens Allgaier Angelika Schobert Manuela Belledin Rolf Jackisch Georg Hertting 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(3):258-266
In the present study we attempted a comprehensive characterization of modulation of noradrenaline release from chick sympathetic neurons. To this purpose sympathetic neurons derived from chick lumbosacral paravertebral ganglia and kept in culture for 7 days were loaded with 0.05 mol/l [3H]-noradrenaline and subjected to electrical field stimulation (36 pulses/3 Hz). Since the released transmitter was partially recaptured, superfusion was usually performed in the presence of (+)-oxaprotiline, an inhibitor of noradrenaline re-uptake. [3H]-Noradrenaline was released in a manner which was dependent on extracellular Ca2+ and sensitive to tetrodotoxin (TTX). -Conotoxin (-CTX; 100 nmol/l) abolished [3H]-noradrenaline release indicating that influx through -CTX-sensitive Ca2+-channels was essential for transmitter release. 1,4-dihydro-2,6-dimethyl-5-nitro4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester ((±)Bay K 8644) and 4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3-nitro-5-pyridinecarboxylic acid isopropyl ester ((±)-202-791), agonists at L-type voltage sensitive Ca2+-channels (VSCCs), increased noradrenaline release and induced, in addition, an overflow of tritium which was Ca2+-dependent and prevented by the presence of TTX. The L-type VSCC antagonists (–)-202-791 and (+)-4-(4-benzofurazanyl)-1,4-dihydro2,6-dimethyl-3,5-pyridinedicar boxylic acid methyl, isopropyl ester ((+)-PN 200–110) diminished [3H]-noradrenaline release. These data suggest that L-type VSCCs, probably located on the cell body of the neuron, play an additional role in modulation of release. The full 2-adrenoceptor agonists 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline ( UK-14,304) and noradrenaline significantly inhibited noradrenaline release, whereas clonidine, a partial a2-agonist, produced only a slight inhibition even at 10 mol/l. The facilitation of noradrenaline release observed in the presence of the 2-adrenoceptor antagonist rauwolscine was very low in comparison to that obtained with brain slices and isolated smooth muscle tissues. These results corroborate the observation that noradrenaline release from chick sympathetic neurons is regulated by an 2-adrenoceptor which needs further subtype characterization. The experiments were mostly performed at 25°C, since a rise in temperature to 37°C increased the resting outflow, but not the evoked overflow of tritium, approximately 4-fold. In the presence of pargyline to block monoamine oxidase, however, the temperature-dependent enhancement was diminshed and the release showed properties comparable to those observed at 25°C (with respect to TTX-sensitivity, Ca2+ dependence and modulation via 2-adrenoceptors). In addition to the 2-adrenoceptors, we detected inhibitory -adrenoceptors, opioid and receptors, and P2 purinoceptors as well as facilitatory prostaglandin (PG) E receptors. No indication was found for a functional relevance of 5-hydroxytryptamine (5-HT), opioid , PGD, adenosine A1 or glutamate receptors. In conclusion, electrically evoked noradrenaline release from cultured chick sympathetic neurons shows the properties of action-potential-induced transmitter release and is bidirectionally regulated by various substances. Therefore, sympathetic neurons in culture offer the possibility to investigate directly the mechanisms bringing about receptor-coupled modulation of transmitter release.Abbreviations ATP
adenosine 5-triphosphate
- Bay K 8644
1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester
- DAGO
(d-Ala2,N-methyl-Phe4,Gly-ol5)-enkephalin
- DPDPE
(d-Pen 2,5)-enkephalin
- 5-HT
5-hydroxytryptamine
- -CTX
-conotoxin
- KRBB
modified Krebs-Ringer bicarbonate buffer
- NMDA
N-methyl-d-aspartic acid
- PG
prostaglandin
- PN 200-110
4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxy lic acid methyl, isopropyl ester
- R-PIA
R(–)-N6-(2-phenyl-isopropyl)-adenosine
- TTX
tetrodotoxin
- U-50,488H
trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzene acetamide
- UK-14,304
5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline
- VSCC
voltage sensitive Ca2+-channel
- 202-791
4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3-nitro-5-pyridinecarboxylic acid isopropyl ester
Correspondence to: C. Allgaier at the above address 相似文献
65.
Tachykinin receptors mediate atropine-resistant rat duodenal reflex contractions in vivo 总被引:2,自引:0,他引:2
Sandro Giuliani Manuela Tramontana Alessandro Lecci Carlo Alberto Maggi 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(3):327-335
The study aimed to establish the possible role of tachykinins as mediators of atropine-resistant reflex contractions evoked by balloon distension in the proximal duodenum of urethane-anesthetized, guanethidine (34 mol/kg s.c.)-pretreated rats. Distension of the balloon with a small amount (0.2–0.3 ml) of saline induced the appearance of phasic rhythmic contractions (about 11 mmHg in amplitude) which were promptly suppressed by either atropine (3 mol/kg i.v.) or hexamethonium (28 mol/kg i.v.). Despite the continuous i.v. infusion of atropine (2 mol/h), low-amplitude rhythmic phasic contractions recovered, which were promptly suppressed by hexamethonium, to indicate the involvement of an atropine-resistant excitatory reflex. The amplitude of these atropine-resistant contractions was increased to about 4–5 mmHg by further distension of the balloon (0.4–0.6 ml) : under these conditions, the atropine-resistant contractions undergo a progressive fading. The fading was prevented by i.v. administration of the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME, 55 mol/h), to provide a suitable baseline (amplitude of contractions was 7–8 mmHg) for studying the effect of tachykinin receptor antagonists.I.v. administration of the selective tachykinin NK2 receptor antagonists, MEN 10,627 (10–100 nmol/kg) and SR 48968 (100–300 nmol/kg) or of the selective NK1 antagonist SR 140333 (100 nmol/kg), at doses which do not affect the duodenal contractions induced by acetylcholine (5.5 µmol/kg i.v.), produced a prompt and long lasting suppression of the atropine-resistant reflex duodenal contractions produced by balloon distension in urethane-anesthetized rats, whilst SR 48965 (300 nmol/kg), the enantiomer of SR 48968 devoid of NK2 receptor blocking activity, was without effect.I.v. administration of the selective NKi receptor agonists [Sar9] substance P sulfone and septide or of the NK2 receptor selective agonist, Ala8] neurokinin A(4–10) produced dose-dependent contractions of the duodenum. SR 140333 (100 nmol/kg i.v.) selectively antagonized the duodenal contractions produced by [Sar9] substance P sulfone and septide without affecting those produced by [Ala8] neurokinin A(4–10). On the other hand, MEN 10,627 (30–100 nmol/kg i.v.) and SR 48968 (100–300 nmol/kg i.v.) but not SR 48965 (300 nmol/kg i.v.) antagonized, at a comparable extent, duodenal contractions induced by both the selective NK2 and NK1 receptor agonists.We conclude that endogenous tachykinins are involved in mediating atropine-resistant reflex contractions evoked by distension of the rat duodenum in vivo: both NK1 and NK2 receptors are activated by endogenous ligands to produce NANC contractions of rat duodenum in vivo. However, the contractile response to i.v. administered NK1 receptor agonists, [Sar9] substance P sulfone and septide, may involve the release of mediators producing smooth muscle contraction via NK2 receptors. 相似文献
66.
Lori E Shapiro Sandra R Knowles Elizabeth Weber Manuela G Neuman Neil H Shear 《Drug safety》2003,26(3):187-195
OBJECTIVE: To evaluate cross reactivity between sulfonamide antimicrobials and celecoxib in patients with histories of allergies to sulfonamide antimicrobials. METHODS: Immunocompetent patients with a history of sulfonamide antimicrobial allergy who were being considered for therapy with celecoxib were prospectively enrolled. Sulfamethoxazole and trimethoprim skin prick and intradermal testing and/or an in vitro lymphocyte toxicity assay were performed. If skin testing was negative, an oral challenge with sulfamethoxazole and trimethoprim was performed. Oral challenges with celecoxib were administered to all patients. RESULTS: Twenty-eight immunocompetent patients (26 female; mean age 60 years) were evaluated. History of sulfonamide antimicrobial allergy included urticaria (n = 7), cutaneous eruptions (n = 9), and other (n = 12). Four of the 28 patients who were skin prick tested were positive to sulfamethoxazole and two of the ten patients who underwent in vitro testing were positive to sulfamethoxazole. All 28 patients were administered celecoxib and tolerated the medication. Phone call follow up in 25 patients disclosed that 15 patients continued to take celecoxib, while five patients did not take celecoxib following the oral challenge, and five discontinued celecoxib due to adverse effects, lack of drug efficacy or physician preference. CONCLUSIONS: Confusion exists regarding the potential for cross reactivity between sulfonamide antimicrobials and other sulfonamide-containing compounds. The six sulfonamide-allergic patients tolerated celecoxib uneventfully. This pilot study supports the hypothesis that the potential for cross-reactivity between celecoxib and sulfonamide antimicrobials appears to be low. However, further investigations are required to confirm this. 相似文献
67.
Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes. 总被引:1,自引:0,他引:1
Beatriz Martinez-Delgado Barbara Meléndez Marta Cuadros Javier Alvarez Jose Maria Castrillo Ana Ruiz De La Parte Manuela Mollejo Carmen Bellas Ramon Diaz Luis Lombardía Fatima Al-Shahrour Orlando Domínguez Alberto Cascon Mercedes Robledo Carmen Rivas Javier Benitez 《Clinical cancer research》2004,10(15):4971-4982
PURPOSE: T-Cell lymphomas constitute heterogeneous and aggressive tumors in which pathogenic alterations remain largely unknown. Expression profiling has demonstrated to be a useful tool for molecular classification of tumors. EXPERIMENTAL DESIGN: Using DNA microarrays (CNIO-OncoChip) containing 6386 cancer-related genes, we established the expression profiling of T-cell lymphomas and compared them to normal lymphocytes and lymph nodes. RESULTS: We found significant differences between the peripheral and lymphoblastic T-cell lymphomas, which include a deregulation of nuclear factor-kappaB signaling pathway. We also identify differentially expressed genes between peripheral T-cell lymphoma tumors and normal T lymphocytes or reactive lymph nodes, which could represent candidate tumor markers of these lymphomas. Additionally, a close relationship between genes associated to survival and those that differentiate among the stages of disease and responses to therapy was found. CONCLUSIONS: Our results reflect the value of gene expression profiling to gain insight about the molecular alterations involved in the pathogenesis of T-cell lymphomas. 相似文献
68.
Aldo Becciolini Manuela Balzi Paola Faraoni Elena Tisti Giorgia Zappoli Thyrion Valentino Giach Luca Bandettini Christopher S. Potten 《Acta oncologica (Stockholm, Sweden)》1998,37(1):65-71
Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt. 相似文献
69.
Kirsti A Bocskay Deliang Tang Manuela A Orjuela Xinhua Liu Dorothy P Warburton Frederica P Perera 《Cancer epidemiology, biomarkers & prevention》2005,14(2):506-511
Molecular and traditional epidemiology studies have indicated a possible relationship between in utero environmental exposures and increased risk for childhood cancers, especially acute leukemias. Chromosomal aberrations have been associated with environmental exposures and cancer risk in adults. In order to more clearly define the association between prenatal exposures to carcinogenic polycyclic aromatic hydrocarbons (PAH) and chromosomal aberrations, chromosomal aberration frequencies were measured in a subset of 60 newborns from the Columbia Center for Children's Environmental Health (CCCEH) Prospective Cohort Study. The subset was composed of African American and Dominican, nonsmoking mother-newborn pairs residing in low-income neighborhoods of New York City, who were exposed to varying levels of airborne PAHs. Prenatal exposure was assessed by questionnaire, personal air monitoring during the third trimester, and PAH-DNA adducts in umbilical cord blood. Chromosomal aberrations were measured in cord blood lymphocytes by fluorescence in situ hybridization. PAH-DNA adducts were not associated with chromosomal aberrations. However, airborne PAHs were significantly associated with stable aberration frequencies in cord blood (P < 0.01). Moreover, stable aberration frequencies were significantly higher among African American newborns compared with Dominican, despite no significant differences in PAH exposure. These results show for the first time an association between prenatal exposure to airborne carcinogenic PAHs and chromosomal aberrations in cord blood, suggesting that such prenatal exposures have the potential to cause cytogenetic damage that has been related to increased cancer risk in other populations. If confirmed, this finding may open new avenues for prevention. 相似文献
70.
DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk 下载免费PDF全文
Allison Hodge Manuela Bianca Assumma Chol‐Hee Jung Jessica Chung Francesca Fasanelli Florence Guida Gianluca Campanella Marc Chadeau‐Hyam Kjell Grankvist Mikael Johansson Ugo Ala Paolo Provero Ee Ming Wong Jihoon Joo Dallas R. English Nabila Kazmi Eiliv Lund Christian Faltus Rudolf Kaaks Angela Risch Myrto Barrdahl Torkjel M. Sandanger Melissa C. Southey Graham G. Giles Mattias Johansson Paolo Vineis Gianluca Severi 《International journal of cancer. Journal international du cancer》2017,140(1):50-61
DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐valuepooled = 4 × 10?17), cg03636183 in the F2RL3 gene (p‐valuepooled = 2 × 10 ? 13), cg21566642 and cg05951221 in 2q37.1 (p‐valuepooled = 7 × 10?16 and 1 × 10?11 respectively), cg06126421 in 6p21.33 (p‐valuepooled = 2 × 10?15) and cg23387569 in 12q14.1 (p‐valuepooled = 5 × 10?7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐valuesheterogeneity ≤ 1.8 x10 ? 7), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk. 相似文献