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Effects of adding potassium iodate to milk before UHT treatment. ii. iodate-induced proteolysis during subsequent aseptic storage.

The addition of potassium iodate to milk at 9.1 mM before UHT treatment resulted in rapid breakdown of alpha s- and beta-casein during subsequent aseptic storage. Maximum rates of proteolysis were observed at storage temperatures of 37-45 degrees C, but the reaction was strongly inhibited by storage at 55 degrees C and by increased holding time at 140 degrees C during the UHT sterilization. Iodate-induced proteolysis of purified alpha s1-and beta-casein was detected only with solutions in the serum phase of raw milk; no proteolysis occurred with solutions in 0.1 M-phosphate buffer (pH 6.7) or in milk ultrafiltrate, irrespective of whether whey proteins and lactose were also added. Thus, it appears that iodate increased the activity of one or more proteolytic components which were present in milk and were unable to pass through an ultrafiltration membrane. However, it is unlikely that iodate acts by increasing the activity of proteinases produced by contaminant bacteria; the presence of iodate did not affect the activity of a proteolytic enzyme isolated from Pseudomonas fluorescens PM-1. Furthermore, iodate promoted protein breakdown during storage of milk drawn aseptically from the cow and subsequently UHT processed. It is suggested that iodate increased the activity of native milk proteinases, other than plasmin which was inactivated by UHT treatment, possibly by preventing thiol-disulphide exchange reactions during the heating process.

Animals

The effect of sodium iodate and melanin on the formation of glyoxylate.

Sodium iodate damages retinal pigment epithelium specifically, but the reason for this specificity is not well understood. The work reported here describes an effect of sodium iodate on melanin, a major component of the retinal pigment epithelium. Sodium iodate increases the ability of melanin to convert glycine to glyoxylate. Almost ten times as much glyoxylate is formed when sodium iodate is present compared to the amount formed with melanin alone, although iodate alone does not convert glycine to glyoxylate. A chemical reaction between sodium iodate and melanin is suggested as a partial explanation of the specificity of iodate toxicity towards retinal pigment epithelium.

Animals

Effect of sodium iodate injection on the development of galactose cataract in the rat.

The effect of sodium iodate injection on the development of galactose cataract in the rat was investigated clinically and biochemically. Galactose cataracts were induced in animals which had been injected with a single dose of sodium iodate and compared with those given a saline injection. The degeneration of retinal pigment epithelium was observed electron microscopically after sodium iodate injection. A slit lamp examination of the lens showed that, in animals injected with sodium iodate, galactose-associated lens alterations progressed faster, and mature cataract development was achieved earlier than in the saline-injected animals. Biochemical data which indicated a significantly higher concentration of Na+ and lower concentration of K+ in lenses of sodium iodate-injected animals confirmed the above clinical data. The level of galactitol was higher in lenses of sodium iodate-injected than those of saline-injected animals. Acceleration of the development of galactose cataract following sodium iodate injection is apparently due to the higher level of galactose entering the aqueous humor because of breakdown of blood-ocular barriers.

Animals

The effect of sodium iodate on the blood-retinal and blood-brain barriers.

Both active transport through and permeability of the blood-retinal barrier (BRB) are affected by sodium iodate, while the blood-brain barrier (BBB) is more resistant. We studied the effect of sodium iodate on facilitated diffusion through the two barriers. The retinal (RUI) and brain (BUI) uptake indices were determined for D-glucose and two neutral amino acids in normal and sodium iodate-treated rats. The integrity of the barriers was estimated by RUI and BUI for L-glucose and by measuring tissue uptake of L-glucose after an intravenous injection. We found that 30 mg/kg sodium iodate had no effect on transport through or permeability of the BBB, while 20 mg/kg significantly (P < 0.02) reduced transport of D-glucose, but not amino acids, through the BRB 1 h after injection. After 24 h both 20 mg/kg and 30 mg/kg sodium iodate caused a significant disruption of the BRB (P < 0.005 and P < 0.001, respectively). Thus, sodium iodate selectively affects the carrier for D-glucose in the BRB but not in the BBB. The presence of an epithelial part in the BRB, the retinal pigment epithelium, may explain the difference between the two barriers.

Animals

Combined action of intraaxonal iodate and external sea anemone toxin ATX II on sodium channel inactivation of frog nerve fibres.

Voltage clamp experiments were done on single myelinated nerve fibres of the frog, Rana esculenta, with 10 mM TEA+ in the external solutions to block potassium channels. Iodate (20, 40 or 100 mM KIO3) was applied to the axoplasmic side of the nodal membrane by diffusion from a cut internode. The effect of 20 mM started within a few minutes and reached a stationary value after ca. 20 min which was maintained for another 15 min. The size of the effect was independent of the iodate concentrations tested. Iodate action could not be reversed even after only a 2-min application. When the effect was fully established, iodate increased the faster time constant of inactivation ca. 1.2 times, the slower one ca. 1.7 times. Iodate also induced a persistent (for seconds) INa component that was, at the end of a 15-ms pulse (I15ms), 6% of the early peak INa of the control. Experiments with conditioning prepulses revealed a non-monotonic h infinity -V curve in iodate with finite h infinity values throughout. Increasing [Ca2+]0 from 2 to 10 mM shifted peak INa (V) and I15ms (V) by 10-15 mV to more positive potentials. In contrast, as shown in previous experiments, I15ms induced by sea anemone toxin ATX II was nearly abolished (h infinity approximately equal to 0) for 60 less than V less than 80 mV on increasing [Ca2+]0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of adding potassium iodate to milk before UHT treatment. I. Reduction in the amount of deposit on the heated surfaces.

Additions of potassium iodate to milk at 0.05 and 0.1 mM (10 and 20 ppm) before UHT treatment markedly reduced the rate at which pressure built up during processing. This permitted the use of longer processing times before unacceptable pressures were reached in the heat exchangers. Iodate reduced the amount of protein deposited, particularly in the higher temperature sections of the plant, but had no effect on the deposition of minerals. The more compact nature of the highly mineral deposits offered less resistance to the flow path. Reduction in the amount of protein deposited is likely to be caused by increased denaturation of beta-lactoglobulin and oxidation of heat activated sulphydryl groups by the iodate, thus reducing the formation of high molecular weight polymers of sulphur-containing proteins at the heated surfaces. Increasing the level of sulphydryl groups in the milk through the addition of L-cysteine-HCl caused an increase in the amount of deposit formed during UHT treatment. Whilst little detrimental effect on the quality of milk resulted from additions of iodate at 0.05 mM, milks with 0.1 mM-iodate became bitter during subsequent aseptic storage. Bitterness was a result of iodate-induced proteolysis of casein.

Animals

[The formation of iodate as a reason for the decrease of efficiency of iodine containing disinfectants (author's transl)].

Methods are given to calculate the iodate equilibrium concentrations in aqueous solutions of iodine, containing additional iodide as well as the reaction times concerning the transformation of iodine to iodate. Using the results, which have been obtained evaluating in this manner solutions of triiodide (CI2 = CI- = 10(-6)--10(-1) M/l) as well as 0.03 M iodine solutions containing varying amounts of iodide (0--0.12 M/l) the following conclusions concerning the stability of iodine containing disinfecting agents can be made; 1. Below pH 6 a decrease of the disinfecting effectiveness owing to the formation of iodate can be excluded. 2. Above pH 7 the formation of iodate, whose extent depends extremely on the pH-value as well as the iodide concentration, has to be regarded very carefully. Raising the pH-value lowers the stability (iodate formation increases) while raising the iodide concentration improves the stability (iodate formation is reduced). 3. Because of the stabilizing effect of the iodide ion, provided that its concentration is high enough, the opposite effect of the pH-value can be overcompensated and as a result of this iodine containing agents can exhibit a stability sufficient for practice also in the weak alkaline range (pH less than 9).

Chemical Phenomena

[Pathologic response of the weak damaged retinal pigment epithelium (RPE)--affected by sodium iodate (NaIO3)].

We examined the cellular responses of the retinal pigment epithelium (RPE) damaged by sodium iodate. RPE was damaged by intravenous administration of sodium iodate, 10mg per kg body weight, in rats. This dose of the agent damaged RPE weakly. Twenty-four hours after the administration of sodium iodate, polystyrene particles were injected into the subretinal space trans-sclerally. Rats were sacrificed at 6 hours to 4 days after injection of particles. Twenty four hours after injection of sodium iodate, RPE were weakly damaged. The cell organelles were swollen and ruptured, but cell structures were not destroyed. Then particles were injected into the subretinal space, RPE did not phagocytize the particles until 24 hours after the injection of particles. After 48 hours, RPE showed proliferation. After 4 days, RPE formed thick multilayers in the subretinal space and transformed to spindle shapes, and RPE underwent metaplasia to fibroblast-like cells. However proliferation of RPE was not marked. RPE cells weakly damaged by sodium iodate showed delay in phagocytosis of the particles and decrease in proliferation and metaplasia to fibroblast-like cells.

Animals

Salt iodation in Kenya for national prophylaxis of iodine deficiency disorders.

This survey was conducted to monitor and evaluate the extent of salt iodation in Kenya in 1990/91. 799 salt samples were collected from 40 districts/municipalities in Kenya out of a possible 44. The samples originated from 16 different local manufacturers/packers. 35.4% of the salt samples were from a single manufacturer, and were available in all the districts/municipalities. 127 (15.9%) samples complied with the legislation of 168.5g/kg. Five samples had exceptionally high iodate--a mean of 8147.1g/kg. The mean iodate content of all samples analysed was 151 mg/kg. Uniformity of iodation was lacking as indicated by high standard deviations. Two manufacturers had iodate content complying with the minimum 168.5mg/kg required by the legislation.

Deficiency Diseases

L-cystein protects the pigment epithelium from acute sodium iodate toxicity.

Intravenous sodium iodate damages the retinal pigment epithelium, causing immediate loss of the electroretinogram c-wave and eventual pigmentary retinopathy. L-cystein, an agent that enhances the c-wave, has been reported to prevent the late development of pigmentary degeneration. We found in rabbits that L-cystein given 30 min before, or simultaneously with (but not 30 min after) sodium iodate also blocks the loss of the c-wave. This result occurred at doses of L-cystein lower than those needed to produce enhancement of the c-wave, suggesting that these two actions of L-cystein may be independent. The iodate-blocking action of L-cystein may depend on chemical interaction.

Animals

Gating in iodate-modified single cardiac Na+ channels.

Elementary Na+ currents were recorded at 19 degrees C during 220-msec lasting step depolarizations in cell-attached and inside-out patches from cultured neonatal rat cardiocytes in order to study the modifying influence of iodate, bromate and glutaraldehyde on single cardiac Na+ channels. Iodate (10 mmol/liter) removed Na+ inactivation and caused repetitive, burst-like channel activity after treating the cytoplasmic channel surface. In contrast to normal Na+ channels under control conditions, iodate-modified Na+ channels attain two conducting states, a short-lasting one with a voltage-independent lifetime close to 1 msec and, likewise tested between -50 and +10 mV, a long-lasting one being apparently exponentially dependent on voltage. Channel modification by bromate (10 mmol/liter) and glutaraldehyde (0.5 mmol/liter) also included the occurrence of two open states. Also, burst duration depended apparently exponentially on voltage and increased when shifting the membrane in the positive direction, but there was no evidence for two bursting states. Chemically modified Na+ channels retain an apparently normal unitary conductance (12.8 +/- 0.5 pS). Of the two substates observed, one of them is remarkable in that it is mostly attained from full-state openings and is very short living in nature; the voltage-independent lifetime was close to 2 msec. Despite removal of inactivation, open probability progressively declined during membrane depolarization. The underlying deactivation process is strongly voltage sensitive but, in contrast to slow Na+ inactivation, responds to a voltage shift in the positive direction with a retardation in kinetics. Chemically modified Na+ channels exhibit a characteristic bursting state much shorter than in DPI-modified Na+ channels, a difference not consistent with the hypothesis of common kinetic properties in noninactivating Na+ channels.

Animals

Effects of sodium iodate on the electroretinogram c-wave in the cat.

The c-wave of the vitreal electroretinogram decreased in amplitude and was replaced by a slow, polarity reversed potential following an i.v. infusion of sodium iodate, as first described by Noell. Intraretinal recordings showed that the negative-going c-wave, induced by iodate (30 mg/kg), was composed of reduced slow pIII and trans-epithelial c-wave. The effects of iodate on these components may originate from direct effects on the retinal pigment epithelial cells, namely, a large decrease in the trans-epithelial resistance. Other factors could have contributed to the change in the c-wave amplitude.

Animals

Transport of fluorescein in the rabbit eye after treatment with sodium iodate.

The outward active transport and the inward permeability of the blood-retinal barrier were studied in the rabbit eye after i.v. administration of sodium iodate. The active transport was evaluated from the half-time of disappearance of the vitreous fluorescein following intravitreal administration, and the inward permeability was evaluated from the vitreous concentration of fluorescein monoglucuronide after i.v. administration. The half-time of the vitreous fluorescein was 3.5 +/- 0.3 (mean +/- S.D.) hr, and 3.9 +/- 0.2 hr before and within 6 hr after iodate administration, respectively. After 24 hr, the half-time was 11.7 +/- 1.7 hr, similar to that of fluorescein monoglucuronide, 12.0 +/- 2.7 hr. The vitreous and the anterior chamber concentration of fluorescein monoglucuronide was measured at 1 hr after the i.v. dye injection. The vitreous concentration in the rabbits given iodate 3 hr before the dye injection was significantly greater than in the normal eyes, while the anterior chamber concentration was not different. Since fluorescein is rapidly metabolized to fluorescein monoglucuronide, differences in parameters determined using systemic fluorescein under two treatments or in disease states may be the result of alteration of the dynamics of fluorescein, fluorescein monoglucuronide, or both.

Animals

Studies on the handling of retinotoxic doses of iodate in rabbits.

Accumulation of iodate in eye tissues and fluids as a possible explanation of the retinotoxic effect of iodate has been studied by intravenous injection of NaIO3(30 mg/kg), 125IO-3 and 131I- in rabbits. 125IO-3 was determined in fluids and tissue extracts by precipitation with BaCl2 after addition of KIO3. 125IO-3 was rapidly broken down in blood (T 1/2 = 14 min.). 125IO-3 was not present in aqueous humour, vitreous or extracts from retina, choroid + pigmentary epithelium or liver. Concentrations of 125I were comparable in blood, choroid + pigmentary epithelium and liver tissue while in vitreous and aqueous humour low concentrations of 125I were found which, however, increased gradually during 5 hrs after injection to reach levels comparable with blood levels of 125I. Retina had a low concentration of 125I. The ratio 125I/131I (R) in blood decreases during the first 60 min. after injection followed by a slow rise. R in retina, choroid + pigmentary epithelium and liver was the same as in blood at the same time after injection. During the first 80 min. after injection R was higher in vitreous than in blood while it was lower in aqueous humour than in blood. At longer times after injection R was identical in the three fluids. The investigation has been supplemented with whole body scintigraphy of rabbits injected with NaIO3(30 mg/kg) and 131IO-3 or 131I-. The reduction kinetics of IO-3 to I- by some body fluids, tissues, cystein and glutathione was also studied. It is concluded that the retinotoxic effect of iodate is not due to accumulation of IO-3 in eye tissues, but more likely to damage to biochemical mechanisms involved in the reduction of IO-3 to I-.

Adipose Tissue

Changes in the juxtapapillary retinal pigment epithelium following intravenous injection of sodium iodate. A light and electron microscopic study using horseradish peroxidase as a tracer.

The effect of an intravenous injection of sodium iodate on the retinal pigment epithelium immediately surrounding the optic nerve head has been investigated using horseradish peroxidase as a morphological tracer. A sodium iodate injection leads to a necrotic reaction of practically the complete retinal pigment epithelium. The juxtapapillary pigment epithelium, however, showed only attenuation and depigmentation without any necrotic reaction 4 and 12 days after the injection. Twenty-six days following the injection the epithelium had almost normalized. The result of this study thus demonstrates a noteworthy resistance of the juxtapapillary retinal pigment epithelium against the sodium iodate effect. At no stage was there a clear indication of a breakdown of the permeability barrier constituted by the juxtapapillary retinal pigment epithelium. Horseradish peroxidase moved into the peripapillary sensory retina by lateral diffusion from the surrounding retina and diffused into the optic nerve head proper, confirming the presence of a diffusional pathway through the Kuhnt intermediary tissue.

Animals

Specific conversion of s4 U to U in Escherichia coli tRNA by iodate oxidation.

The minor nucleoside 4-thiouridine in Escherichia coli tRNA is transformed selectively to uridine by iodate oxidation at acidic pH. The four major nucleotides were found to be inert under these conditions. The iodate oxidation appears to be more specific than the previous conversion methods reported, and has the advantage that it does not affect the chargeability of most tRNA.

Escherichia coli