Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new neomycin research articles will be listed here shortly after becoming available to us.
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Medical research on neomycin
Cardiac Microvascular Endothelial Cells Express a Functional Ca-Sensing Receptor.
J Vasc Res. 2008 Jun 24; 46(1): 73-82
Berra Romani R, Raqeeb A, Laforenza U, Scaffino MF, Moccia F, Avelino-Cruz JE, Oldani A, Coltrini D, Milesi V, Taglietti V, Tanzi F
The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores.
Highly enriched cardiomyocytes from human embryonic stem cells.
Cytotherapy. 2008; 10(4): 376-89
Xu XQ, Zweigerdt R, Soo SY, Ngoh ZX, Tham SC, Wang ST, Graichen R, Davidson B, Colman A, Sun W
BACKGROUND: Current efforts to direct differentiation of human embryonic stem cells (hESC) into a particular cell lineage usually lead to a heterogeneous cell population with only a fraction of the desired cell type present. We show the generation of an essentially pure population of human cardiomyocytes from hESC using lineage selection. METHODS: A construct comprising the murine alpha-myosin heavy chain (alpha-MHC) promoter driving the neomycin-resistance gene was introduced into hES3 cells to generate stable transgenic lines. Transgenic hESC lines were differentiated into cardiomyocytes and subjected to G418 selection. Both G418-selected and non-selected cardiomyocytes were characterized by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The teratoma-forming potential of differentiated cells was assessed by injection of about 2 million cells into the hind limb muscle of SCID mice. Results After cardiac differentiation and antibiotic selection in a suspension culture process, more than 99% of the transgenic cells showed immunoreactivity to alpha-MHC and alpha-actinin; this enrichment efficiency was observed for independent transgenic cell lines. Quantitative RT-PCR analysis revealed high levels of enrichment for cardiac-specific messages in the selected population. Importantly, injection of selected cells into six SCID mice resulted in no apparent teratoma formation, in contrast to differentiated but non-selected controls. DISCUSSION: Our results represent a significant step toward scalable production of pure human cardiomyocytes from stable, expandable hESC lines that will facilitate the development of cell therapies, safety pharmacology and drug discovery.
Molecular recognition of a DNA:RNA hybrid: Sub-nanomolar binding by a neomycin-methidium conjugate.
Bioorg Med Chem Lett. 2008 May 28;
Shaw NN, Xi H, Arya DP
A novel neomycin-methidium conjugate was synthesized. The covalent linkage of the aminoglycoside to an intercalator, a derivative of ethidium bromide, results in a new conjugate capable of selective recognition of the DNA:RNA hybrid duplex. Spectroscopic methods: UV, CD, fluorescence, and calorimetric techniques: DSC and ITC were used to characterize the sub-nanomolar binding displayed by the conjugate for the DNA:RNA hybrid duplex, poly(dA):poly(rU).
J Feline Med Surg. 2008 Jun 20;
Tudor EG, Lee AC, Armato DG, Bowman DD
A 2-year-old female domestic shorthair cat on the island of Saipan was presented to a local veterinarian for headshaking. Otoscopic examination showed mild erythema of the right tympanic membrane, but was otherwise unremarkable. Headshaking resolved with topical gentamicin/betamethasone/clotrimazole therapy; however, erythema persisted. Further otoscopy revealed movement of the erythematous region, which was in fact the red-colored strongylid nematode, Mammomonogamus auris, residing within the middle ear. Myringotomy and a saline flush were performed under heavy sedation. A silastic tube was inserted into the incision and the worms were retrieved by applying negative pressure. Follow-up treatment included topical thiabendazole/dexamethasone/neomycin ointment as well as selamectin. Mammomonogamus auris has previously been documented only three times, once each in China, Sri Lanka and Japan. This is the first report of M auris in cats from Saipan.
J Pharmacol Sci. 2008 Jun; 107(2): 181-9
Dalbó S, Goulart S, Horst H, Pizzolatti MG, Ribeiro-do-Valle RM
The present study investigates the mechanisms related to the endogenous nitric oxide synthase (eNOS) activation in the relaxant effects of a proanthocyanidin-rich fraction (PRF), obtained from Croton celtidifolius Baill barks, in rat thoracic aorta rings with endothelium. In vessels pre-contracted with phenylephrine (Phe), PRF (0.1 - 100 mug/mL) induced a concentration-dependent relaxation. This effect was significantly reduced by endothelium denudation, by N(omega)-nitro-L-arginine, and by 1H[1,2,3]oxadiazolo[4,3-alpha]quinoxalin. However, the vasorelaxant effect was not altered by indomethacin, atropine, tetraethylammonium, and charybdotoxin plus apamin. In thoracic aorta rings pre-contracted with phorbol-12,13-dibuyrate, PRF also induced a concentration-dependent relaxation. The PRF-induced relaxation disappeared in the absence of extracellular calcium in the medium and decreased significantly in the presence of lanthanum. A sulfhydryl alkylating agent, N-ethylmaleimide, and a phospholipase C (PLC) blocker, neomycin, significantly decreased PRF-induced vasorelaxation. In vessels pre-contracted with Phe, the PRF-induced vasorelaxant effect was not altered by quinacrine and ONO-RS-082, genistein and thyrphostin A-23, GF109203, and pertussis toxin and cholera toxin. The results suggest that the PRF-induced vasorelaxant effect is endothelium-dependent and involves the NO/cGMP pathway. We hypothesize that the activation of eNOS is due to an increase of intracellular calcium derived from PLC activation and an N-ethylmaleimide sensitive pathway.
Ca-dependent Nonsecretory Vesicle Fusion in a Secretory Cell.
J Gen Physiol. 2008 Jun 18;
Wang TM, Hilgemann DW
We have compared Ca-dependent exocytosis in excised giant membrane patches and in whole-cell patch clamp with emphasis on the rat secretory cell line, RBL. Stable patches of 2-4 pF are easily excised from RBL cells after partially disrupting actin cytoskeleton with latrunculin A. Membrane fusion is triggered by switching the patch to a cytoplasmic solution containing 100-200 muM free Ca. Capacitance and amperometric recording show that large secretory granules (SGs) containing serotonin are mostly lost from patches. Small vesicles that are retained (non-SGs) do not release serotonin or other substances detected by amperometry, although their fusion is reduced by tetanus toxin light chain. Non-SG fusion is unaffected by N-ethylmaleimide, phosphatidylinositol-4,5-bis-phosphate (PI(4,5)P(2)) ligands, such as neomycin, a PI-transfer protein that can remove PI from membranes, the PI(3)-kinase inhibitor LY294002 and PI(4,5)P(2), PI(3)P, and PI(4)P antibodies. In patch recordings, but not whole-cell recordings, fusion can be strongly reduced by ATP removal and by the nonspecific PI-kinase inhibitors wortmannin and adenosine. In whole-cell recording, non-SG fusion is strongly reduced by osmotically induced cell swelling, and subsequent recovery after shrinkage is then inhibited by wortmannin. Thus, membrane stretch that occurs during patch formation may be a major cause of differences between excised patch and whole-cell fusion responses. Regarding Ca sensors for non-SG fusion, fusion remains robust in synaptotagmin (Syt) VII-/- mouse embryonic fibroblasts (MEFs), as well as in PLCdelta1, PLC delta1/delta4, and PLCgamma1-/- MEFs. Thus, Syt VII and several PLCs are not required. Furthermore, the Ca dependence of non-SG fusion reflects a lower Ca affinity (K(D) approximately 71 muM) than expected for these C2 domain-containing proteins. In summary, we find that non-SG membrane fusion behaves and is regulated substantially differently from SG fusion, and we have identified an ATP-dependent process that restores non-SG fusion capability after it is perturbed by membrane stretch or cell dilation.
Eur Arch Otorhinolaryngol. 2008 Jun 17;
Abelardo E, Pope L, Rajkumar K, Greenwood R, Nunez DA
The objective of the study was to determine if the addition of topical antibiotic increases the efficacy of topical steroid in controlling otitis externa. A double-blind randomised controlled trial was performed from February 2003 to April 2005 in an otolaryngology emergency clinic (acute urban teaching hospital) in the United Kingdom. Patients were followed up for 2 weeks. Forty-five adults with otitis externa based on the presence of oedema, discharge or debris in the outer ear canal were recruited. The patients were randomised to one of the two treatment groups, namely using betamethasone sodium phosphate 0.1% (Vista-Methasone) or betamethasone sodium phosphate 0.1% with neomycin sulphate 0.5% (Vista-Methasone N), and were instructed to use the trial medication at three drops three times a day for 2 weeks. Subjects' visual analogue symptom scores (blockage, pain, discharge, and itching) for otitis externa pre-treatment (day 0) and post-treatment (day 15), percentage changes in visual analogue symptom scores as a result of treatment, proportion of patients whose symptom scores failed to improve or deteriorated on treatment were analysed. The two experimental arms demonstrated statistically similar presenting symptom scores at recruitment (mean symptom scores of 19.2 for betamethasone group and 28.7 for betamethasone-neomycin group). The mean symptom score change in response to treatment was 82.8 and 47.8% in the betamethasone-neomycin and betamethasone-alone groups, respectively. There was no statistically significant difference between the groups in median percentage symptom score change in response to treatment. All patients in the betamethasone-neomycin group showed symptom improvement but in the betamethasone alone group, five patients got worse (Fishers exact, P = 0.05). Topical antibiotic-steroid combination therapy is superior to steroid-alone treatment for symptomatic control of otitis externa.
Biorheology. 2007; 44(5-6): 349-60
Cheng M, Liu X, Li Y, Tang R, Zhang W, Wu J, Li L, Liu X, Gang Y, Chen H
Shear stress can modulate endothelial cell function by regulating gene expression. We have previously demonstrated that low shear stress (4.2 dyn/cm(2)) induces the expression of interleukin-8 (IL-8) gene in endothelial cells. The present study was undertaken to further investigate both the effects of shear stress on IL-8 expression and the mechanisms controlling IL-8 mRNA up-regulation in human umbilical vein endothelial cells (HUVEC). We show that shear stress (from 2.23 to 19.29 dyn/cm(2)) induces the IL-8 expression at both the mRNA and protein levels by stimulating transcription. In order to determine the possible contribution of G protein, HUVEC were pretreated with an inhibitor of G-protein activation, GDPbetaS, which abrogated the low shear stress-induced IL-8 gene expression. Such gene expression was also partially inhibited by the tyrosine kinase inhibitor (tyrphostin-25) and in addition by EGTA, BATPA/AM (the intracellular Ca(2+) chelator), Verapamil (a Ca(2+) channel blocker), cAMP-dependent protein kinase inhibitor (KT5720) and phospholipase C inhibitor (neomycin). However, the cGMP-dependent protein kinase inhibitor, KT5823, had no effect on such expression. These findings therefore demonstrate the involvement of several signaling molecules, including tyrosine kinase, G protein, calcium, phospholipase C, and cAMP-dependent protein kinase, in the low shear stress-induced IL-8 gene expression.
Acta Cir Bras. 2008 Jun; 23(3): 262-269
Magalhães MS, Fechine FV, Macedo RN, Monteiro DL, Oliveira CC, Brito GA, Moraes ME, Moraes MO
PURPOSE: The aim of the study was to determine the effect of a combination of medium chain triglycerides (caprylic, capric, caproic and lauric acids), linoleic acid (essential fatty acid), vitamins A and E and soy lecithin, through a morphometric study, on the wound healing kinetics of experimental cutaneous ulcers. METHODS: A total of 45 male Wistar rats were used, in which a skin flap of total thickness with an area of 4 cm(2) was removed. The animals were divided randomly into 3 groups of 15 rats each, Control, Reference and Test groups, which were treated topically with 0.9% NaCl, a preparation of clostebol combined with neomycin sulfate and the test formulation, respectively. The wound areas were measured by digital planimetry at days zero, 3, 7 and 12 postoperative. Based on the wound area, we determined the degree of tissue repair and mean rate of repair at different time intervals. RESULTS: At day 3, an expansion of the wound area was observed in the Reference group and slight contraction in the Control and Test groups. On the subsequent days, the healing process, according to the degree of repair, proceeded in a linear manner, such that, at day 12, the healed area reached 77.95% of the initial ulcerated region in the Control group, 78.40% in the Reference group and 83.49% in the Test group, showing no significant differences. The overall mean rate of repair was equally similar at 12 days of treatment: 25.79 mm(2)/dia in the Control group, 25.42 mm(2)/dia in the Reference group and 27.38 mm(2)/dia in the Test group. CONCLUSION: The test preparation, applied topically on the experimentally induced cutaneous ulcers in rats, did not accelerate the process of tissue repair by secondary union.
Cre-mediated recombination in mouse Clara cells.
Genesis. 2008 Jun; 46(6): 300-7
Li H, Cho SN, Evans CM, Dickey BF, Jeong JW, DeMayo FJ
Clara cells are nonciliated secretory cells lining the respiratory epithelium and are easily identified by the expression of Clara cell secretory protein (CCSP). To investigate molecular mechanism(s) regulating Clara cell function in the lungs, Cre recombinase was inserted into exon 1 of the CCSP, generating two novel mouse models, CCSP(Cre-Neo) and CCSP(Cre). These two models differ only by the inclusion of the neomycin resistance gene. These mice were bred to the R26R reporter mouse to investigate the tissue and cell specificity of Cre-mediated recombination. The efficiency of Cre recombination in the CCSP(Cre) mouse model was higher than in the CCSP(Cre-Neo) mouse model. Recombination was detected at D 4.5 in CCSP(Cre-Neo)/R26R mice and at D 0.5 in CCSP(Cre)/R26R mice. The CCSP(Cre-Neo) and CCSP(Cre) mouse models provide valuable tools for the ablation of genes in the postnatal mouse Clara cells.