In vitro comparative cytotoxicity study of a novel biocidal iodo-thiocyanate complex.

Novel biocides, which avoid the induction of cross-resistance to antibiotics, are an urgent societal requirement. Here, we compared the cytotoxic and bactericidal effects of a new antimicrobial agent, the iodo-thiocyanate complex (ITC), with those of the common antiseptics, hydrogen peroxide (H2O2), povidone iodine (PVP-I) and Lugol's iodine (Lugol). The antimicrobials were co-incubated for 10 min with HeLa and Escherichia coli cells in the presence and absence of organic matter (Dulbecco's modified Eagle's medium, supplemented with 10% fetal bovine serum). The cytotoxic concentrations of ITC were equivalent to its bactericidal concentrations (7.8 µg ml-1). By contrast, cytotoxic effects of H2O2, PVP-I and Lugol were apparent at concentrations lower than their bactericidal concentrations (250, 250 and 125 µg ml-1, respectively). The cellular effects of ITC were not quenched by organic matter, unlike the other antiseptics. ITC, PVP-I and Lugol had hemolytic effect on horse erythrocytes at high concentrations, while H2O2 showed no hemolysis. ITC, at 30 or 300 µg ml-1, did not cause DNA breakage in HeLa cells as assessed by an in vitro comet assay in the absence of S9 metabolic activation, whereas H2O2 caused extensive single-strand DNA breaks. The pronounced antimicrobial potency of ITC and its favorable cytotoxicity profile suggests that ITC should be considered for antiseptic applications.

Injection in temporomandibular joint of rats. Description of technical protocol.

The development of animal models for research has been very diffused. Osteoarthritis is a joint degenerative pathology that induces cartilage erosion, chondrocyte proliferation and osteophyte formation. The aim of this paper is to present a technical procedure to perform the injection of monosodium iodine acetate in the temporomandibular joints of rats to generate osteoarthritis and to contribute to future research analysis related to pathology progression and proper treatment performance. The use of rat models may be a complex process because of their size, but they can be compared to the human temporomandibular joint due to the similar characteristics and the possibility of performing diagnosis and treatment protocols in order to detect this pathology.

Identification, toxicity and control of iodinated disinfection byproducts in cooking with simulated chlor(am)inated tap water and iodized table salt.

Chlorine/chloramine residuals are maintained in drinking water distribution systems to prevent microbial contamination and microorganism regrowth. During household cooking processes (e.g., soup making), the residual chlorine/chloramines in tap water may react with the iodide in iodized table salt to form hypoiodous acid, which could react with remaining natural organic matter in tap water and organic matter in food to generate iodinated disinfection byproducts (I-DBPs). However, I-DBPs formed during cooking with chloraminated/chlorinated tap water are almost completely new to researchers. In this work, by adopting precursor ion scan of m/z 127 using ultra performance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry, many new polar I-DBPs formed during cooking with chloraminated/chlorinated tap water were detected and proposed with structures, of which 3-iodo-4-hydroxybenzaldehyde, 3-iodo-4-hydroxybenzoic acid, 3-iodo-4-hydroxy-5-methylbenzoic acid, diiodoacetic acid, 3,5-diiodo-4-hydroxybenzaldehyde, 3,5-diiodo-4-hydroxybenzoic acid, 2,6-diiodo-4-nitrophenol, 2,4-diiodo-6-nitrophenol, and 2,4,6-triiodophenol were confirmed with standard compounds. With the aid of ultra fast liquid chromatography/ion trap-time of flight-mass spectrometry, molecular formula identification of five new I-DBPs (C8H5O4I, C7H4NO4I, C8H5O5I, C7H4NO5I, and C8H6O3I2) was achieved. A developmental toxicity with a recently developed sensitive bioassay was conducted for the newly identified I-DBPs, suggesting that phenolic I-DBPs (except for iodinated carboxyphenols) were about 50-200 times more developmentally toxic than aliphatic I-DBPs. The major I-DBPs in a baseline simulated cooking water sample were determined to be from 0.72 to 7.63 µg/L. Polar I-DBPs formed under various disinfection and cooking conditions were compared, and suggestions for controlling their formation were provided.

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.

Formation of toxic iodinated disinfection by-products from compounds used in medical imaging.

Iodinated X-ray contrast media (ICM) were investigated as a source of iodine in the formation of iodo-trihalomethane (iodo-THM) and iodo-acid disinfection byproducts (DBPs), both of which are highly genotoxic and/or cytotoxic in mammalian cells. ICM are widely used at medical centers to enable imaging of soft tissues (e.g., organs, veins, blood vessels) and are designed to be inert substances, with 95% eliminated in urine and feces unmetabolized within 24 h. ICM are not well removed in wastewater treatment plants, such that they have been found at elevated concentrations in rivers and streams (up to 100 µg/L). Naturally occurring iodide in source waters is believed to be a primary source of iodine in the formation of iodo-DBPs, but a previous 23-city iodo-DBP occurrence study also revealed appreciable levels of iodo-DBPs in some drinking waters that had very low or no detectable iodide in their source waters. When 10 of the original 23 cities' source waters were resampled, four ICM were found--iopamidol, iopromide, iohexol, and diatrizoate--with iopamidol most frequently detected, in 6 of the 10 plants sampled, with concentrations up to 2700 ng/L. Subsequent controlled laboratory reactions of iopamidol with aqueous chlorine and monochloramine in the absence of natural organic matter (NOM) produced only trace levels of iodo-DBPs; however, when reacted in real source waters (containing NOM), chlorine and monochloramine produced significant levels of iodo-THMs and iodo-acids, up to 212 nM for dichloroiodomethane and 3.0 nM for iodoacetic acid, respectively, for chlorination. The pH behavior was different for chlorine and monochloramine, such that iodo-DBP concentrations maximized at higher pH (8.5) for chlorine, but at lower pH (6.5) for monochloramine. Extracts from chloraminated source waters with and without iopamidol, as well as from chlorinated source waters with iopamidol, were the most cytotoxic samples in mammalian cells. Source waters with iopamidol but no disinfectant added were the least cytotoxic. While extracts from chlorinated and chloraminated source waters were genotoxic, the addition of iopamidol enhanced their genotoxicity. Therefore, while ICM are not toxic in themselves, their presence in source waters may be a source of concern because of the formation of highly toxic iodo-DBPs in chlorinated and chloraminated drinking water.

The effect of transcatheter injections on cell viability and cytokine release of mononuclear cells.

BACKGROUND AND PURPOSE: Several studies suggest that various types of cellular therapies enhance recovery after stroke in animal models. IA-based delivery of cells to the brain is under investigation for stroke, but it is unknown whether cells are injured as a result of being injected through a catheter or exposed to iodinated contrast medium or solutions containing heparin. MATERIALS AND METHODS: We assessed the effect of catheterization with the Excelsior SL-10 catheter or exposure to heparin or iodine contrast on human bone marrow MNCs. Viability and cell injury were assessed by trypan blue exclusion, caspase-3 activity, and lipid peroxidation. Cellular function of MNCs was assessed by their production and release of VEGF, IL-10, and IGF-1. RESULTS: Flow rates of 10 million cells from 0.5 to 2 mL/min did not alter MNC viability; however, 5 mL/min of MNCs did reduce viability by 19%. Iodine and low-dose heparin exposure did not affect cell viability; however, high-dose heparin was cytotoxic. Catheter delivery at 2 mL/min did not affect levels of VEGF, IL-10, or IGF-1. CONCLUSIONS: MNCs do not appear to be damaged by heparin, iodine contrast, and the Excelsior SL-10 catheter at flow rates up to 2 mL/min. However, higher flow rates did reduce viability, and high-dose heparin did cause cell death.

A picture of polar iodinated disinfection byproducts in drinking water by (UPLC/)ESI-tqMS.

Iodinated disinfection byproducts (DBPs) are generally more toxic than their chlorinated and brominated analogues. Up to date, only a few iodinated DBPs in drinking water have been identified by gas chromatography/mass spectrometry. In this work, a method for fast selective detection of polar iodinated DBPs was developed using an electrospray ionization-triple quadrupole mass spectrometer (ESI-tqMS) by conducting precursor ion scan of iodide at m/z 126.9. With such a method, pictures of polar iodinated DBPs in chlorinated, chloraminated, and chlorine-ammonia treated water samples were achieved. By coupling state-of-the-art ultra performance liquid chromatography (UPLC) to the ESI-tqMS, structures of 17 iodinated DBPs were tentatively proposed. The results fully demonstrate that, with respect to the DBP number/levels among the three disinfection processes, chloramination generally generated the most/highest iodinated DBPs, chlorination generally produced the fewest/lowest iodinated DBPs, and chlorine-ammonia sequential treatment formed iodinated DBPs lying in between; the numbers of iodinated DBPs in chloraminated Suwannee River Fulvic Acid (SRFA) and Humic Acid (SRHA) were nearly the same, but the levels of aliphatic iodinated DBPs were higher in the chloraminated SRFA while the levels of aromatic iodinated DBPs were higher in the chloraminated SRHA; a couple of nitrogenous iodinated DBPs were found in chloramination and chlorine-ammonia treatment. The ratio of total organic iodine levels in chlorine-ammonia sequential treatment and chloramination could be expressed as a function of the lag time of ammonia addition.

[Etiology of iodinated radiocontrast nephrotoxicity and its attenuation by beraprost].

Radiocontrast nephropathy (RCN) is a major complication after radiographical examination with iodinated contrast media (CM). Although little is known about the mechanism of RCN, a direct toxic action on renal cells and/or decrease in renal blood flow are considered to be implicated in the pathogenesis of the disease/the condition, A large number of vasodilatory agents, including endothelin antagonists, adenosine antagonists, atrial natriuretic peptide, calcium channel blockers, dopamine, dopamine D1 receptor agonist fenoldopam, and prostaglandin E1 have been tried clinically to prevent RCN, however, most of them have failed. Although prophylactic effects of antioxidant N-acetylcysteine have recently been reported by several investigators, only hydration is a universally accepted protocol to prevent it. In our recent in vitro and in vivo study, we have elucidated that CM induced apoptosis of renal tubular cells through the reduction in Bcl-2 expression and the subsequent activation of caspase-9 and caspase-3. Moreover, we found that CM caused an increase in ceramide content in renal tubular cells, which leads to apoptosis by inhibiting the phosphorylation of Akt and cAMP responsive element binding protein (CREB) and the subsequent reduction in Bcl-2 expression. The inhibitor of ceramide synthase, fumonisin B1, reversed both the elevation of ceramide content and renal cell injury induced by CM. On the other hand, a prostacyclin analog beraprost prevented RCN in mice by the increase of endogenous cAMP and subsequent CREB phosphorylation resulted in enhancement of Bcl-2 expression. These findings suggest that ceramide synthesis inhibitor or beraprost is potentially useful for the prophylaxis of RCN.

Nanoparticulate carrier containing water-insoluble iodinated oil as a multifunctional contrast agent for computed tomography imaging.

Contrast-enhanced computed tomography (CT) imaging is a valuable and routine strategy for the clinical diagnosis of various diseases. However, all current CT contrast agents are liquids, so they flow through the blood vessels and disappear very quickly by extravasation. If it were possible to make a blood-compatible particulate contrast agent, we could highlight a particular tissue by either passive or active targeting. In this work, Pluronic F127 and a naturally iodinated compound, Lipiodol, were used to form radiopaque nanoreservoir structures. The resultant nanoparticles have a stable structure at high concentrations, sufficient X-ray absorption, a safety profile similar to or better than that of Iopromide, and a longer circulation time than commercial iodinated preparations. The utility of the resultant radiopaque nanoparticles as a contrast agent was tested using micro-SPECT/CT imaging in vivo. Together with the very good solubility of hydrophobic drugs (e.g., Taxol) in Lipiodol, these results suggest the possibility that these particulate structures and their bioconjugates could become functional CT contrast agents that could deliver therapeutic agents to a particular tissue.

An in vitro evaluation of the cytotoxicity of various endodontic irrigants on human gingival fibroblasts.

The purpose of this study was to measure the cytotoxicity of six endodontic irrigants on cultured gingival fibroblasts using the CyQuant assay. Human gingival fibroblasts were grown in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bovine serum at 37 degrees C and 5% CO(2). At confluence, cells were split, plated in 96-well plates and incubated for 24-h to allow attachment. The following irrigants were tested at various concentrations: Sodium hypochlorite (NaOCl); iodine potassium-iodide (IKI); Betadine scrub (BS); calcium hydroxide [Ca(OH)2]; chlorine dioxide (SCD) and DMEM (positive control). Experimental groups were compared by the logarithmic difference between the clinical and LD50 concentrations of a particular irrigant. The results showed that IKI and Ca(OH)2 were significantly less cytotoxic than SCD, NaOCl, and BS. In conclusion, IKI and Ca(OH)2 are well tolerated by human gingival fibroblasts.

In vitro antibacterial effect of calcium hydroxide combined with chlorhexidine or iodine potassium iodide on Enterococcus faecalis.

Several studies have shown a higher success rate of root canal therapy when the canal is free from bacteria at the time of obturation. Treatment strategies that are designed to eliminate this microflora should include agents that can effectively disinfect the root canal. Enterococcus faecalis is often associated with persistent endodontic infections. While in vivo studies have indicated calcium hydroxide to be the most effective all-purpose intracanal medicament, iodine potassium iodide (IKI) and chlorhexidine (CHX) may be able to kill calcium hydroxide-resistant bacteria. Supplementing the antibacterial activity of calcium hydroxide with IPI or CHX preparations was studied in bovine dentine blocks. While calcium hydroxide was unable to kill E. faecalis in the dentine, calcium hydroxide combined with IKI or CHX effectively disinfected the dentine. The addition of CHX or IKI did not affect the alkalinity of the calcium hydroxide suspensions. It may be assumed that combinations also have the potential to be used as long-term medication. Cytotoxicity tests using the neutral red method indicated that the combinations were no more toxic than their pure components.

The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro.

A deterioration of renal function is one preoccupying complication of iodinated radiocontrast agents in clinical practice. These compounds have direct toxic effects on renal cells, which are only in part related to their physicochemical properties. The hyperosmolal monomeric ionic radiocontrast agents, like diatrizoate, have the highest toxicity, whereas renal cells are less affected by (nonionic) compounds with reduced osmolality. The toxic effects include cellular energy failure, a disruption of calcium homeostasis, a disturbance of tubular cell polarity and programmed cell death (apoptosis). The molecular mechanisms of the direct cytotoxicity are still unclear, although oxidative stress has been implicated. Radiocontrast cytotoxicity has been demonstrated in glomerular mesangial cells and in renal epithelial cells in vitro. In vivo, the direct cellular toxicity of radiocontrast agents is compounded with alterations in blood flow and/or viscosity, ultimately resulting in renal medullary hypoxia, which is a hallmark feature of the complex clinical syndrome of radiocontrast nephropathy.