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Photochemistry of halogen pyrimidines: iodine release studies.

The feasibility of using direct iodide (I-) measurements to monitor the photochemistry of the halogenated pyrimidines 5-iodocytosine and 5-iodouracil and their corresponding deoxynucleosides was examined. Radiation from either a germicidal lamp (lambda = 254 nm) or a sunlamp (lambda greater than 290 nm) was employed to induce homolytic splitting of the carbon-iodine bond and the release of iodine atoms. These atoms combine to form I2 which reacts with water to ultimately form I- and iodate (IO3-). The formation of I- was followed using either high performance liquid chromatography with electrochemical detection or a specific ion electrode. IO3- was assayed spectroscopically following its conversion to triiodide. The yields of I- relative to starting material destroyed were either close to the theoretical limit of 83% or higher depending upon (a) the compound being irradiated, (b) the irradiation wavelength and (c) the extent of exposure. Yields of iodide greater than 83% are generally accounted for by a concomitant reduction in the yield of iodate such that the sum I(-) + IO3- is approx. 100%. Because iodate is photochemically reduced to iodide by 254 nm but not sunlamp irradiation, exhaustive irradiation at 254 nm converts all of the iodate present to iodide. These studies have application to the use of photochemical methods for quantitating the percent substitution of iodinated pyrimidines in DNA, and should be useful in following the photochemistry of IdUrd and IdCyd substituted DNA.

Cytosine↗

Iodine deficiency persists in the Zanzibar Islands of Tanzania.

BACKGROUND: Iodine is an essential micronutrient for normal human growth and development. It is estimated that more than 1.6 billion people live in iodine-deficient environments, yet there are still some countries and areas where the prevalence of iodine-deficiency disorders is unknown. OBJECTIVE: To establish the prevalence of iodine-deficiency disorders in the Zanzibar Islands, a community assumed to have ready access to iodine-rich seafoods. METHODS: In a cross-sectional study, 11,967 schoolchildren were palpated for goiter prevalence, a subsample was evaluated for urinary iodine concentration, and the availability of iodated salt was assessed at the household and retail levels. RESULTS: The mean total goiter prevalence was 21.3% for Unguja and 32.0% for Pemba. The overall median urinary iodine concentration was 127.5 microg/L. For Unguja the median was 185.7 microg/L, a higher value than the median of 53.4 microg/L for Pemba (p < .01). The household availability of iodated salt was 63.5% in Unguja and 1.0% in Pemba. The community was not aware of the iodine-deficiency problem and had never heard of iodated salt. CONCLUSIONS: The inadequate intake of iodine documented in the Zanzibar Islands belies the common assumption that an island population with access to seafood is not at risk for iodine-deficiency disorders. We urge health planners to implement mandatory salt iodation and education efforts to alleviate the situation.

Adolescent↗

[Effects of supplementation of different kinds of iodine on the antioxidative ability of retina in iodine deficient rats].

OBJECTIVE: To study the effects of iodine supplementation (in different kinds and doses) on the antioxidative ability of retina in iodine deficient rats. METHODS: One hundred and twenty eight iodine deficient Wistar rats were randomly divided into four groups, normal dose of iodate, normal dose of iodide, high dose of iodate and high dose of iodide. Concentration of serum thyroid hormones, including total TT(3) and total TT(4), were estimated by radioimmunoassay. GSH-Px, SOD, TAOC activities and MDA content in the retina were determined using biochemical methods in the 22nd week of iodine supplementation. RESULTS: Statistical analysis showed that a significant difference in TT(3) level of serum was observed between animals treated with different doses. Serum TT(3) level in the groups treated with high doses was significantly higher than those with normal doses. However, no statistical difference could be detected at TT(4) level between animals treated with different doses. Different kind of iodine did not affect the level of thyroid hormones. Statistical analysis showed that a difference in SOD activity of retina was observed between animals treated with different doses. SOD activity in the groups with normal doses was significantly higher than that in groups with larger doses. Retina TAOC activity was significantly higher in groups treated with iodide than that in groups of iodate. Although there was no statistical difference in GSH-Px activity between different groups, it showed the same tendency as the SOD and TAOC activities, i.e. GSH-Px activity in the groups of normal doses was higher than that in the groups of high doses. GSH-Px activity in groups of iodide was higher than that in the groups of iodate. There was no significant difference in MDA content among these four groups. CONCLUSIONS: Different iodine and doses have certain effects on the antioxidative ability of retina in iodine deficient rat. The rats supplemented potassium iodide at normal dose showed higher antioxidative ability of the retina than those of the others.

Animals↗

[Effect of chronic mild and moderate iodine excess on thyroid anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats].

OBJECTIVE: To investigate the effects of chronic mild and moderate iodine excess on thyroid oxidative injury and anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats. METHODS: Four-week-old Wistar rats were fed with iodine deficient diet for three months to make iodine deficient goiter models, then divided randomly into three groups: iodine deficient control group (Group IDC) fed with double distilled water, iodine-supplement group I (Group IS I) fed with potassium iodate solutions with the iodine concentrations of 100 microg/L, and iodine-supplement group II (Group IS II), fed with potassium iodate solution with the iodine concentrations of 330 microg/L. Another four-week-old Wistar rats were fed with normal diet for three months, and then divided randomly into three groups: normal control group (NC) fed with double distilled water, iodine-excess group I (IEI) fed with potassium iodate solution with the iodine concentration of 300 microg/L, and iodine-excess group II (Group IEII), fed with potassium iodate solution with the iodine concentration of 660 microg/L. 1, 2, 4, 8, and 24 weeks after treatment samples of urine were collected to detect the median urine iodine (MUI), samples of plasma were collected from the hearts of 8-14 rats from each group and then rats were killed. Their thyroid glands were taken out to measure the wet weight and made into homogenate. Biochemical method was used to measure the activities of glutathione-peroxidase (GSH-P(X)) and superoxide dismutase (SOD) as well as the contents of malonyldialdehyde (MDA) and H2O2 in the homogenates of thyroid glands. RESULTS: The GSH-P(X) activity 2 weeks after treatment of Group IS II was significantly lower than that of Group IDC (P < 0.05), and the GSH-P(X) activity 4 weeks after treatment of Group IS I was significantly lower than that of Group IDC (P < 0.001). The activities of GSH-P(X) 4, 8, and 24 weeks after treatment of Groups IS I and IS II were all lower than those of Group C at the same time points significantly (P < 0.001, < 0.01, and < 0.05 respectively). The activities of SOD were decreased gradually in Groups IS I and IS II and were significantly lower than those of Group IDC since 8 weeks after treatment (P < 0.001 or < 0.05). The SOD activities in thyroid glands of Groups IEI and IEII since 8 weeks after treatment decreased significantly in comparison with Group NC (all P < 0.01 or < 0.001). The contents of H2O2 in thyroid glands of Groups IS I and IS II were significantly lower than those of Group IDC at different time points (P < 0.001, < 0.01, or < 0.05), and were significantly lower than those of Group NC 8 and 24 weeks after treatment (P < 0.001 or < 0.01). The contents of MDA in thyroid glands since 2 weeks after treatment of Group IEI were all significantly lower than those of Group IDC at the same time points (all P < 0.05), and the content of MDA in thyroid glands since 1 week after treatment of Groups IS II were all significantly lower than those of Group IDC at the same time points (all P < 0.05). CONCLUSION: Supplementation of 100 microg/L and 330 microg/L iodine on iodine deficiency Wistar rats may alleviate the oxidative injury but weaken the anti-oxidative protection of thyroid. The anti-oxidative protection of thyroid glands of non-iodine deficiency Wistar rats may also be weakened by supplementation of 300 microg/L and 660 microg/L iodine.

Animals↗

Chemically modified cardiac Na+ channels and their sensitivity to antiarrhythmics: is there a hidden drug receptor?

Elementary Na+ currents were recorded at 19 degrees C in inside-out patches from cultured neonatal rat cardiocytes. In analyzing the sensitivity of chemically modified Na+ channels to several class 1 antiarrhythmic drugs, the hypothesis was tested that removal of Na+ inactivation may be accompanied by a distinct responsiveness to these drugs, open channel blockade. Iodate-modified and trypsin-modified cardiac Na+ channels are noninactivating but strikingly differ from each other by their open state kinetics, a O1-O2 reaction (tau open(1) 1.4 +/- 0.3 msec; tau open(2) 5.4 +/- 1.1 msec; at -40 mV) in the former and a single open state (tau open 3.0 +/- 0.5 msec; at -40 mV) in the latter. Lidocaine (150 mumol/liter) like propafenone (10 mumol/liter), diprafenone (10 mumol/liter) and quinidine (20 mumol/liter) in cytoplasmic concentrations effective to depress NPo significantly can interact with both types of noninactivating Na+ channels to reduce the dwell time in the conducting configuration. Iodate-modified Na+ channels became drug sensitive during the O2 state. At -40 mV, for example, lidocaine reduced tau open(2) to 62 +/- 5% of the control without detectable changes in tau open(1). No evidence could be obtained that these inhibitory molecules would flicker-block the open Na+ pore. Drug-induced shortening of the open state, thus, is indicative for a distinct mode of drug action, namely interference with the gating process. Lidocaine proved less effective to reduce tau open(2) when compared with the action of diprafenone. Both drugs apparently interacted with individual association rate constants, a(lidocaine) was 0.64 x 10(6) mol-1 sec-1 and a(diprafenone) 13.6 x 10(6) mol-1 sec-1. Trypsin-modified Na+ channels also appear capable of discriminating among these antiarrhythmics, the ratio a(diprafenone)/a(lidocaine) even exceeded the value in iodate-modified Na+ channels. Obviously, this antiarrhythmic drug interaction with chemically modified Na+ channels is receptor mediated: drug occupation of such a hypothetical hidden receptor that is not available in normal Na+ channels may facilitate the exit from the open state.

Animals↗

Model system oxidations supporting the crystal growth model of ferritin iron uptake.

Fe2+ is oxidized and taken up by ferritin or ápoferritin in the presence of dioxygen. Iodate causes Fe2+ oxidation and uptake by ferritin, but not by apoferritin. Synthetic iron polymer facilitates Fe2+ oxidation by either dioxygen or iodate. Nitrilotriacetic acid or iminodiacetic acid facilitate oxidation of Fe2+ by oxygen but not by iodate. These results support the crystal growth model of ferritin iron uptake, with iron polymer serving as a model for the ferritin core and aminocarboxylic acids mimicking the metal-binding sites of apoferritin.

Apoferritins↗

Sorption and transport of iodine species in sediments from the Savannah River and Hanford Sites.

Iodine is an important element in studies of environmental protection and human health, global-scale hydrologic processes and nuclear nonproliferation. Biogeochemical cycling of iodine is complex, because iodine occurs in multiple oxidation states and as inorganic and organic species that may be hydrophilic, atmophilic, and biophilic. In this study, we applied new analytical techniques to study the sorption and transport behavior of iodine species (iodide, iodate, and 4-iodoaniline) in sediments collected at the Savannah River and Hanford Sites, where anthropogenic (129)I from prior nuclear fuel processing activities poses an environmental risk. We conducted integrated column and batch experiments to investigate the interconversion, sorption and transport of iodine species, and the sediments we examined exhibit a wide range in organic matter, clay mineralogy, soil pH, and texture. The results of our experiments illustrate complex behavior with various processes occurring, including iodate reduction, irreversible retention or mass loss of iodide, and rate-limited and nonlinear sorption. There was an appreciable iodate reduction to iodide, presumably mediated by the structural Fe(II) in some clay minerals; therefore, careful attention must be given to potential interconversion among species when interpreting the biogeochemical behavior of iodine in the environment. The different iodine species exhibited dramatically different sorption and transport behavior in three sediment samples, possessing different physico-chemical properties, collected from different depths at the Savannah River Site. Our study yielded additional insight into processes and mechanisms affecting the geochemical cycling of iodine in the environment, and provided quantitative estimates of key parameters (e.g., extent and rate of sorption) for risk assessment at these sites.

Adsorption↗

Colorimetric determination of inorganic iodine in fortified culinary products.

The presented colorimetric procedure only requires simple laboratory equipment and is suitable as a routine procedure for checking concentrations of iodine in fortified culinary products. The Moxon and Dixon colorimetric procedure for iodine determination has been optimised for the determination of iodide and iodate in fortified culinary products, always containing high salt levels. The high sensitivity of the method permits a high dilution of the product solutions, thus reducing interferences from the inherent colour of the products. The calibration is linear in the range from 0 to 12 microg L(-1) of iodine with R2 > 0.99. A series of commercial culinary products were used to validate the method. Recoveries of iodine, added as iodide and/or iodate, were generally in the range 100+/-10%. High concentrations of chloride are essential to obtain a complete recovery of iodate. Limit of quantification was estimated to be 2 mg kg(-1) of product, based on 2-3 g of product. Concentrations of iodine determined with this method were similar to those obtained by an ICP-MS procedure.

Colorimetry↗

Biochemical changes in rabbit sclera following destruction of pigment epithelium.

The long-term effect of destruction of the pigment epithelium by sodium iodate on the biochemistry of rabbit sclera was studied in one group with intravenous injection of sodium iodate, and in a second group with injection of sodium iodate into the right eye. Intravenous treatment produced a non-significant increase in the uronic acid concentration. In the second group the untreated fellow eye was microscopically intact, but was shown (as the treated eye) to alter the concentration of uronic acid in different parts of the sclera. All eyes from treated animals exhibited changes in the relative content of the various glycosaminoglycans and in the content of hydroxyproline, hydroxylysine and proline. This work indicates that the pigment epithelium may play a key role in the control mechanism of the scleral connective tissue, and this again has major implications in terms of a possible medical treatment of axial myopia.

Amino Acids↗

Disinfection of microorganisms by use of electrochemically regenerated periodate.

A new method for disinfection of microorganisms by electrochemically regenerated periodate was developed. Oxidation of iodate to periodate was observed at 1.25 V versus a silver/silver chloride electrode in a cyclic voltammogram of potassium iodate. When 1.25 V was applied in 1.0 mM potassium iodate, approximately 4-log inactivation of Escherichia coli was observed in 30 min.

Disinfection↗

Choriocapillaris regeneration in the rabbit: a study with vascular casts.

Vascular casts were made of the choriocapillaris (CC) of rabbits that received sodium iodate intravenously 6-28 days prior to examination, in order to augment studies of CC regeneration in sectioned material. Regeneration of CC was evident 6 days after administration of iodate where zones of spared CC bordered zones of atrophic CC. Venular as well as capillary sprouts created foci of regenerating CC at this border. These foci to create an extended capillary plexus similar to mature CC. The observations corroborate those obtained in sectioned material as regards the geography of the CC response and the origins of new CC during the sodium iodate retinopathy, and provide new information on the way in which CC regenerates.

Animals↗

Dynamic contrast-enhanced MRI measurements of passive permeability through blood retinal barrier in diabetic rats.

PURPOSE: To test the hypothesis that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a useful in vivo measure of passive blood retinal barrier permeability surface area product (BRB PS) in experimental diabetic retinopathy. METHODS: BRB PS (cm(3)/min) was measured using DCE-MRI and Gd-DTPA (MW 590 Da) in urethane-anesthetized control rats, sodium iodate-treated rats, rats receiving intravitreally injected human serum albumin (HSA) or vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), or in rats that were diabetic for 2, 4, 6, or 8 months. RESULTS: Sodium iodate-treated rats exhibited an eightfold increase (P < 0.05) in BRB PS compared to that in control animals. Furthermore, in iodate-treated rats, the average vitreous signal enhancement was linearly dependent on Gd-DTPA dose (r = 0.91, P < 0.0001). Six hours postinjection, VEGF/VPF-treated rats exhibited a threefold increase in BRB PS (P < 0.05) compared to eyes injected with HSA. In 2-, 4-, and 6-month diabetic rats, BRB PS was not significantly different (P > 0.05) from control BRB PS values. After 8 months of diabetes, a twofold increase (P < 0.05) in PS over control PS values was found. DCE-MRI demonstrated that the BRB becomes leaky immediately before death, possibly causing an artificial increase in retinal permeability in methods that require enucleation or retinal isolation to assess permeability. CONCLUSIONS: DCE-MRI provides a sensitive, noninvasive, and linear assay that accurately measures, without potential artifacts associated with death and enucleation, passive BRB PS in experimental diabetes. DCE-MRI BRB PS measurements are expected to provide a useful surrogate marker of drug treatment efficacy.

Animals↗

Chorioretinal diffusion processes following pigment epithelial degeneration.

We studied the effect of sodium iodate-induced pigment epithelial degeneration on chorioretinal diffusion processes. Rabbits received two intravenous injections of sodium iodate at the retinotoxic dose of 22.5 mg. per kilogram over a six- to eight-hour period. Combined horseradish peroxidase tracing technique and electron microscopy were used to compare diffusion processes over a five-week period. Ultrastructural examination of retina twenty-four hours after iodate administration revealed pigment epithelial degeneration, accompanied by disruption of junctional complexes (zonulae occludentes). Peroxidase molecules were found in areas of greater cytoplasmic degeneration and in intercellular spaces up to the level of the external limiting membrane. Ultrastructural observations at later stages revealed similar findings except in the case of Muller cells, 20 per cent of which showed cytoplasmic degeneration and peroxidase uptake. The diffusion barrier was not re-established as the replacement cells did not rebuild zonulae occludentes.

Animals↗

In vivo imaging of breakdown of the inner and outer blood-retinal barriers.

Real-time contrast-enhanced magnetic resonance imaging (MRI) was used to distinguish between experimentally induced breakdown of the vascular (inner) and retinal pigment epithelial (RPE; outer) blood-retinal barrier (BRB) in vivo. Pigmented rabbits were treated with intravenous sodium iodate 30 mg/kg, (a specific RPE cell poison), intravitreal N-ethylcarboxamidoadenosine (NECA) 10(-3) mol/l (which specifically disrupts the vascular BRB), or retinal diode laser photocoagulation. Coronal T1-weighted proton images were acquired in a timed sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Images were analyzed to localize leakage of Gd-DTPA and determine the permeability surface area product normalized per unit area (PS). The pattern of enhancement observed in eyes treated with sodium iodate differed clearly from that in eyes treated with NECA. PS' values were significantly higher in eyes treated with sodium iodate than with NECA. Simultaneous leakage from the outer and inner BRB in eyes treated with dense retinal laser photocoagulation could be localized and quantitated independently.

Adenosine↗

Albumin movement out of the subretinal space after experimental retinal detachment.

PURPOSE: The subretinal fluid of serous retinal detachments contains protein, but little is known about its origin and fate. The authors designed experiments to study the rate and route of albumin movement out of the subretinal space. METHODS: Experimental retinal detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution containing serum levels (approximately 30 mg/ml) of fluorescein isothiocyanate (FITC) albumin into the subretinal space through a micropipette. Subretinal, vitreous, and serum fluid samples were withdrawn 0 to 4 hours later through a similar micropipette and were analyzed for osmolality, FITC albumin content (by fluorophotometry) and FITC+native albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). RESULTS: Albumin injected into the subretinal fluid diffused steadily into the vitreous, and its concentration decreased by approximately 5% per hour. This rate was unaffected by RPE damage. Albumin did not move into the bloodstream unless the RPE was damaged with sodium iodate, and then it crossed the RPE at approximately 25% of the rate at which it moved into the vitreous. Subretinal fluid osmolality remained within the range of 293 to 294 mOsm/kg despite protein movement and the continual absorption of fluid from the detachments. CONCLUSIONS: These results show that albumin in the subretinal space diffuses readily into the vitreous, and subretinal osmolality changes are rapidly equilibrated with the vitreous. Albumin does not cross normal RPE, and it crosses iodate-damaged RPE more slowly than it crosses retina. Thus, there must be a constant supply of albumin if high subretinal concentrations are to be sustained in clinical serous detachments.

Animals↗

Iodine speciation in size fractionated atmospheric particles by isotope dilution mass spectrometry.

An isotope dilution mass spectrometric method has been developed for the accurate and sensitive determination of iodide and iodate in aerosol particles of the atmosphere. The direct iodine speciation has been possible by the use of species specifically (129)I enriched spike solutions and separation of the isotope diluted species by anion exchange chromatography after water extraction of the filters. Size fractionated collection of aerosol particles by a six stage impactor system shows different distributions of iodide and iodate for particles of different size with specific patterns for anthropogenically influenced continental and unpolluted marine aerosols, respectively. The detection limit for particulate iodide and iodate has been (3-5) pg/m(3) for sampling volumes of 3000 m(3). Oil, used for heating plants, could be identified as one but not the only anthropogenic iodine source.

Journal Article↗

Determination of cyclodextrin content using periodate oxidation by capillary electrophoresis.

A simple and general method suitable for the determination of cyclodextrin content in various matrices is described. The proposed method involves selective cleavage of C-C bonds with vicinal hydroxyl groups by means of periodate (Malaprade's reaction). The amount of produced iodate is monitored by capillary electrophoresis. Optimized electrophoretic conditions (20 mM disodium tetraborate with 1 mM tetradecyltrimethylammonium bromide, direct UV detection lambda = 200 nm) ensure complete separation of periodate and iodate ions and sufficient sensitivity towards iodate. Under optimized reaction conditions (2-fold excess of periodate, temperature 70 degrees C) reproducible quantitative results were obtained for alpha-, beta- and gamma-cyclodextrins as model samples. The proposed method was tested on a real sample of acrylamide--2'-O-allyl-beta-CD copolymer. The values of beta-cyclodextrin content were compared with those obtained by reference NMR measurement and were found to be identical.

Cyclodextrins↗

An experimental model of retinal pigment epithelial and neurosensory serous detachment.

PURPOSE: The authors document an animal model of retinal pigment epithelial (RPE) detachments. METHODS: N-ethylmaleimide (NEM) and sodium iodate (sulfhydryl-alkylating agents) were injected into the vitreous of Dutch pigmented rabbits. Subretinal fluid samples were withdrawn 0.5 and 3 hours after NEM injections and analyzed for albumin content by gel electrophoresis. Selected eyes were examined histologically. RESULTS: Injections of 9.2 micrograms NEM caused wrinkling of the retina within 15 minutes, at which time fluorescein angiography revealed multifocal RPE detachments. At this stage, histologic sections showed moderate choroidal edema and RPE detachment. Elevated retinal detachments developed over the next 15 to 25 minutes. Histologic sections showed massive choroidal edema and RPE fragmentation. The albumin concentration of subretinal fluid rose from 60% of serum level at 30 minutes after NEM to 80% after 3 hours. Sodium iodate did not cause choroidal edema or RPE detachment. CONCLUSION: In rabbits, intravitreal NEM causes the rapid appearance of choroidal edema and RPE detachment, followed by serous retinal detachment. The initial effect probably is caused by an alteration of choroidal vascular permeability. The relationship of these effects to sulfhydryl alkylation is unclear because sodium iodate failed to produce RPE detachments. N-ethylmaleimide effects may model aspects of clinical RPE and serous retinal detachments.

Animals↗