scholarly journals Cytotoxic Effect of Antiseptics: Comparison In vitro, In vivo Examination of Strong Acidic Electrolyzed Water, Povidone-iodine, Chlorhexidine and Benzalkonium Chloride

2003 ◽  
Vol 77 (5) ◽  
pp. 316-322 ◽  
Author(s):  
Atsuo IWASAWA ◽  
Yoshiko NAKAMURA
1991 ◽  
Vol 19 (2) ◽  
pp. 263-270
Author(s):  
Haruyoshi Igarashi ◽  
Yasunaga Katsuta ◽  
Yoshiharu Nakazato ◽  
Tohru Kawasaki

We have evaluated a new in vitro opacitometer method as an alternative to the in vivo Draize test for ocular irritancy. Several concentrations of timolol maleate (timolol) with or without 0.005% benzalkonium chloride were applied to porcine isolated corneas which were either intact or with the epithelium, endothelium, or both epithelium and endothelium removed. Corneal opacities were measured using an opacitometer. In general, timolol with benzalkonium chloride caused a greater degree of opacity to develop in the cornea than did timolol alone. At the lower concentrations of timolol, the increased opacity probably represented additive effects of the two compounds. However, at the highest concentration of timolol (5 x 10 2M), there was an enhanced opacification in the presence of benzalkonium chloride, which may have been due to an increase in penetration, particularly through the epithelium. Timolol caused a greater degree of opacity to develop in the isolated intact porcine corneas when the drug was applied to the endothelial surface, than when applied to the epithelial surface or to both the epithelial and endothelial surfaces. However, timolol with benzalkonium chloride caused a greater degree of opacity in the intact cornea, when the drug was applied to both surfaces than when it was applied only to the epithelial or the endothelial surface.


2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
C.A. Lux ◽  
K. Biswas ◽  
M.W. Taylor ◽  
R.G. Douglas

Background: Despite best medical and surgical practice, some cases of chronic rhinosinusitis (CRS) can remain recalcitrant. Bacterial biofilms have been associated with the recalcitrance of sinonasal inflammation. Biofilms are highly resistant to commonly prescribed antibiotics. Accordingly, more effective antimicrobial treatment options are needed to treat refractory CRS. The aim of this study was to determine the in vitro efficacy of neutral electrolysed water (NEW) and povidone-iodine (PVI) against CRS-associated Staphylococcus aureus biofilms. Methods: Mature S. aureus biofilms were grown in a Centre for Disease Control (CDC) biofilm reactor. The antimicrobial activity of NEW, PVI and doxycycline was determined for both planktonic and biofilm cultures of a clinical S. aureus isolate using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC) assays. Results: MICs and MBCs were determined for all antimicrobials. MBC values were similar to MICs for both antiseptics, but doxycycline MBCs were significantly higher than the associated MICs. Biofilms were highly resistant to NEW and doxycycline. The MBEC for doxycycline was between 500 and 1000 µg/mL. NEW was ineffective against biofilms and no MBEC could be determined. In contrast, a concentration of 10% of the commercial PVI solution (10 mg/mL PVI) led to effective eradication of mature biofilms. Conclusion: In this study, only PVI showed promising antibiofilm activity at physiological concentrations. The in vivo efficacy of PVI warrants further investigation of its potential as a treatment for recalcitrant CRS.


2011 ◽  
Vol 1 (1) ◽  
pp. 6 ◽  
Author(s):  
Hayet Belmeskine ◽  
Pauline Brousseau ◽  
Sami Haddad ◽  
Louise Vandelac ◽  
Michel Fournier

The immunotoxicological effects of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/Fs) mixtures on <em>Eisenia andrei </em>earthworms have never been studied. In this work we investigated these effects both for <em>in vitro </em>and <em>in vivo</em> exposure, using the viability and the phagocytic activity of coelomocytes as immunological biomarkers and the flow cytometry was used for analysis. The <em>in vitro </em>exposure revealed a cytotoxic effect of PCDD/Fs mixture (C2) containing 50&yen;10-3 ng/mL of 2, 3, 7, 8-TCDD and an induction of the phagocytic capacity at the mixture (C1) containing 25&yen;10-3 ng/mL of 2, 3, 7, 8-TCDD. In the <em>in vivo </em>filter paper exposure, the immunocompetence of earthworms was assessed after 3 h-exposure to mixtures of PCDD/Fs at the levels of C1, C2, C3 and C4 containing about; 0.05, 0.3, 0.5 and 0.83 ng of 2, 3, 7, 8-TCDD/cm&sup2;, respectively. Morphological observations showed an excessive secretion of mucus and body surface lesions in worms exposed to higher concentrations (C3 and C4), which revealed that these organisms were affected by PCDD/Fs either through skin and/or by feeding. The levels of the extruded cell yield decreased significantly at all the concentrations tested. However, the cell viability was shown to be unaffected by PCDD/Fs concentrations. It was also shown, that exposure to the highest PCDD/Fs concentrations; C2, C3 and C4 inhibited both phagocytic activity and efficiency.


2011 ◽  
Vol 68 (6) ◽  
pp. 1557-1564 ◽  
Author(s):  
Ario Takeuchi ◽  
Masaki Shiota ◽  
Katsunori Tatsugami ◽  
Akira Yokomizo ◽  
Masatoshi Eto ◽  
...  
Keyword(s):  

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Silvia Lorena Montes-Fonseca ◽  
Blanca Sánchez-Ramírez ◽  
Antonia Luna-Velasco ◽  
Carlos Arzate-Quintana ◽  
Macrina Beatriz Silva-Cazares ◽  
...  

Carbon nanotubes (CNTs) are used as carriers in medicine due to their ability to be functionalized with chemical substances. However, cytotoxicity analysis is required prior to use forin vivomodels. The aim of this study was to evaluate the cytotoxic effect of CNTs functionalized with a 46 kDa surface protein fromEntamoeba histolytica(P46-CNTs) on J774A macrophages. With this purpose, CNTs were synthesized by spray pyrolysis and purified (P-CNTs) using sonication for 48 h. A 46 kDa protein, with a 4.6–5.4 pI range, was isolated fromE. histolyticaHM1:IMSS strain trophozoites using an OFFGEL system. The P-CNTs were functionalized with the purified 46 kDa protein, classified according to their degree of functionalization, and characterized by Raman and Infrared spectroscopy.In vitrocytotoxicity was evaluated by MTT, apoptosis, and morphological assays. The results demonstrated that P46-CNTs exhibited cytotoxicity dependent upon the functionalized grade. Contrary to what was expected, P46-CNTs with a high grade of functionalization were more toxic to J774 macrophages than P46-CNTs with a low grade of functionalization, than P-CNTs, and had a similar level of toxicity as UP-CNT. This suggests that the nature of the functionalized protein plays a key role in the cytotoxicity of these nanoparticles.


Author(s):  
Suresh Kumar Ananda Sadagopan ◽  
Nooshin Mohebali ◽  
Chung Yeng Looi ◽  
Mohadeseh Hasanpourghadi ◽  
Ashok Kumar Pandurangan ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 232-232
Author(s):  
Rosa Lapalombella ◽  
Caroline Berglund ◽  
Emilia Mahoney ◽  
Katie Williams ◽  
Shruti Jha ◽  
...  

Abstract Abstract 232 Exportin 1 (CRM1, XPO1) is a nuclear exporter that promotes the transit of tumor suppressor proteins (TSPs) including p53, I-κB, and FOXO3A out of the nucleus, thereby preventing their activity and contributing to disrupted apoptosis and enhanced proliferation. Recently, whole-genome sequencing in patients with CLL allowed the identification of recurrent mutations in a highly conserved region of CRM1 that can potentially affects its gene function, suggesting a direct role for CRM1 in the pathogenesis of CLL (Puente XS, et al: Nature 75:101, 2011). However the role of CRM1 and the consequences of its mutation in the development of CLL have yet to be explored. CRM1 has been shown to be up-regulated in hematologic and various solid tumors, making it a highly attractive molecular target impacting multiple pro apoptotic pathways. KPT-SINEs are new, potent and irreversible small molecule selective inhibitors of nuclear export developed by Karyopharm that specifically and irreversibly bind to CRM1 and block the function of this protein. CLL is characterized by disrupted apoptosis caused both by co-dependent stromal elements and aberrant activation of several survival-promoting signaling/transcriptional pathways including PI3K/Akt, NF-kB, and p53. Because of the distinct subtypes of CLL and multiple signaling pathways dysregulated, a therapeutic agent targeting a single biological pathway is unlikely to be effective. Thus, pursuit of CRM1 inhibition as a novel strategy aimed to restore multiple death pathways is crucial and has broad implications for many types of patients. Our preliminary work demonstrated CRM1 is over-expressed in CLL cells compared to normal B cells at a protein (3 fold, p<0.005) and mRNA level (2.6 fold p=0.014). Inhibition of CRM1 by KPT-185 induced apoptosis in primary patient CLL cells in a dose and time dependent manner (EC50<500nM) while limited cytotoxicity against normal PBMC and isolated B, NK and T cells was observed (EC50 values >20 μM). Additionally, KPT-185 treatment of NK cells had no effect on their function as measured by ability of NK cells to mediate antibody dependent (ADCC) as wekk as direct cytotoxicity. The effect of KPT-185 on T function is currently under evaluation. Nuclear accumulation of FOXO3, p53 and IkB was also observed in primary CLL cells in a time dependent manner as shown by western blot and confocal microscopy. The evaluation of activated target genes is currently ongoing. Given the importance of microenvironmental stimuli on survival of CLL cells and response to therapy, we evaluated the ability of KPT-185 to induce cytotoxicity of CLL cells in the presence or absence of soluble factors such as CPG, CD40L, BAFF, TNF-α, IL-6, or IL-4, which are known to reduce the spontaneous apoptosis associated with CLL cells. KPT-185 treatment abrogated the protection induced by each of these factors suggesting that KPT-SINEs can disrupt signaling from the microenvironment that lead to in vivo CLL cell survival and potentially drug resistance. Interestingly the cytotoxic effect elicited by KPT-185 was enhanced in CPG activated cells (p=0.02). We also tested the ability of KPT-185 to kill CLL cells under coculture conditions with Hs5 stromal cell line. Coculture of CLL cells alone for 48 hours on the Hs5 stromal cell line resulted in a marked reduction of spontaneous apoptosis suggesting a strong protective effect elicited (P<0.001) by the stromal cells. Interestingly the cytotoxic effect mediated by KPT-185 was enhanced under coculture conditions (p=0.013). KPT-185 was also proven to be effective on murine TCL1+ cells (EC50<500nM) in vitro. The in vivo efficacy of this compound and other structurally related analogs is currently being assessed in an ongoing study in theTCL1 mouse model of CLL. In conclusion CRM1 represents a novel target that has not been adequately explored in CLL. KPT-SINEs are a class of promising therapeutic agents with proven selective in vitro activity in CLL cells providing the rationale for developing small molecule, drug-like CRM1 inhibitors for the treatment of this disease. Disclosures: Sandanayaka: Karyopharm Therapeutics: Employment. Shechter:Karyopharm Therapeutics: Employment. McCauley:Karyopharm Therapeutics: Employment. Shacham:Karyopharm: Equity Ownership. Kauffman:Karyopharm: Equity Ownership.


2012 ◽  
Vol 28 (6) ◽  
pp. 2091-2100 ◽  
Author(s):  
NAN YOU ◽  
WEIHUI LIU ◽  
TAO WANG ◽  
RU JI ◽  
XING WANG ◽  
...  

2006 ◽  
Vol 80 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Chu Sheng-hua ◽  
Zhu Zhi-an ◽  
Yuan Xian-hou ◽  
Li Zhi-qiang ◽  
Jiang Pu-cha

2004 ◽  
Vol 15 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Peter Hovstadius ◽  
Elin Lindhagen ◽  
Sadia Hassan ◽  
Kenneth Nilsson ◽  
Helena Jernberg-Wiklund ◽  
...  

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