Delivery of antiseptic solutions by a bacterial cellulose wound dressing: Uptake, release and antibacterial efficacy of octenidine and povidone-iodine.

BACKGROUND: Bacterial nanocellulose (BNC) is considered a promising carrier for various substances and novel approaches using BNC in combination with antiseptics are well documented. However, the difference in the molecular weight of these molecules influences their uptake by and release from BNC. Analysing the diffusion of standard molecules with different weight, e.g. dextrans, offers the possibility to investigate the mobility of various molecules. We aimed to test the use of BNC regarding uptake and release of different standard molecules as well as two commercially available antiseptics for possible applications in future wound dressings. MATERIAL AND METHODS: Diffusion profiles, uptake and release of three FITC-dextran molecules differing in weight as well as octenidine (Octenisept®) and povidone-iodine (Betaisodona®)-based antiseptics were tested with BNC-based wound dressings. Furthermore, the antiseptic efficacy of BNC in combination with antiseptics against Staphylococcus aureus was tested. RESULTS: Uptake and release capacity for FITC-dextran molecules showed a molecular weight-dependent mobility from BNC into an agarose gel. The loading capacity of BNC was also inversely proportional to the molecular weight of the antiseptics. The release test for octenidine showed a sustained and prolonged delivery into a solid matrix, whereas povidone-iodine was released faster. Both antiseptic solutions combined with BNC showed a good dose-dependent efficacy against S. aureus. CONCLUSION: Results obtained from the mobility of FITC-dextran molecules in the BNC matrix could open possible applications for the combination of BNC with other molecules for medical applications. Combination of both tested antiseptics with BNC showed to be an efficient approach to control bacterial infections.

Povidone iodine skin absorption: an ex-vivo study.

Povidone iodine is a water-soluble complex used to disinfect the skin surface and it exerts prolonged germicidal action against a broad spectrum of germs. Indeed, it is often applied on burned skin, large wounds, deep tissues or mucosa. Notably some surgical hand-scrub solutions, which are considered safe antiseptics, contain large amounts of iodine that can be absorbed by skin. The aim of present study was to study the skin absorption of iodine after the application on the skin of povidone-iodine solution, used by health care workers during surgical procedure. We use Franz diffusion static cells with human skin. After 24h from the beginning of our measurement the iodine concentration in the receiving compartment was 11.59±6.3µg/cm(2). The medium flux calculated was 0.73±0.33µg/cm(2)/h with a lag time of 8.9±1.5h. These in vitro results confirmed that povidone iodine could pass through the skin in a relevant amount that can explain the clinical findings in burned or surgically treated patients. In professional use the repetitive contact with povidone iodine, also as soap, can cause iodine skin permeation that must be considered when the washing procedures are repeated more than 20 times a day.

Sealability of ultrashort-pulse laser and manually generated full-thickness clear corneal incisions.

PURPOSE: To compare the sealability and geometry of full-thickness clear corneal incisions (CCIs) created manually or with an ultrashort-pulse laser. SETTING: Lensar, Inc., Orlando, Florida, USA. DESIGN: Experimental study. METHODS: Ex vivo human donor globes were randomly assigned to groups for the manual or laser-generated full-thickness CCIs. Standard 3-plane manual or laser incisions were made in 22 globes. Incision geometry was measured using an optical coherence tomographer. Sealability was assessed by inflating globes to physiologic intraocular pressure (IOP) and pressing a mechanical plunger into the globe to deform the globe and increase IOP until leakage was detected using the Seidel test. The test of sealability at lowered IOP was performed similarly; the anterior chamber was monitored for signs of ingress of a povidone-iodine 10% solution placed externally. RESULTS: The mean IOP elevation at which leakage occurred was higher for the laser than for manually generated full-thickness CCIs, indicating that the mean sealability was better for the laser. However, t tests showed that there was no statistically significant difference in the mean IOP elevation at which full-thickness incision leakage occurred between manual and laser full-thickness CCIs. Thus, the sealability of the manual and laser full-thickness CCIs were equivalent for the incision geometry tested. The laser full-thickness CCIs were statistically closer to target geometry and showed less variability than the manual full-thickness CCIs. CONCLUSIONS: The sealability of laser and manual full-thickness CCIs were statistically equivalent. The laser full-thickness CCIs were more consistent in geometry and closer to the target incision geometry.

Povidone iodine: features of critical systemic absorption.

Povidone iodine (PI), a skin antiseptic, is sometimes used internally but this procedure exposes to potentially lethal iodine absorption. Indeed, a 41-year-old woman, with no relevant medical history, developed a transient hypotension, anuric renal failure, hemolysis, coagulopathy and uterine infarction after intra-uterine injection of PI as a dye to check the fallopian tube patency (hydrotubation). Iodemia peaked at 6929 µg/dL (normal range 3.4-8.0 µg/dL), and decreased over the 9 days of renal replacement therapy. Extreme caution should be exercised when PI is in contact with a mucosa, the early recognition of iodine toxicity being of utmost importance to rapidly prompt renal replacement therapy. The main purpose of this report is to highlight the clinical features of PI absorption, whatever the route of administration.

Hydrogen peroxide and povidone-lodine solution--a dangerous combination.

When mixed with povidone-iodine solution, hydrogen peroxide can release enough oxygen to cause sealed waste containers to burst open. Such risks can also result from using a sealed container to collect hydrogen peroxide that has mixed with body fluids (for instance, in a debridement procedure). Staff should be instructed to avoid both practices.

Relationship between glycocalyx and povidone-iodine resistance in Pseudomonas aeruginosa (ATCC 27853) biofilms.

Biofilm-embedded bacteria are generally more resistant to antimicrobial agents than are planktonic bacteria. Two possible mechanisms for biofilm resistance are that the glycocalyx matrix secreted by cells in a biofilm reacts with and neutralizes the antimicrobial agent and that the matrix creates a diffusion barrier to the antimicrobial agent. This study was therefore conducted to examine the relationship between glycocalyx and enhanced povidone-iodine resistance in biofilms of Pseudomonas aeruginosa (ATCC 27853). Biofilms were generated by inoculation of polycarbonate membranes with broth-grown cells and incubation of them on the surfaces of nutrient agar plates. The quantities of glycocalyx material per cell were found not to be significantly different between biofilm and planktonic samples. Transmission electron microscopy showed that the distributions of glycocalyx material around cells differed in biofilm and in planktonic samples. Addition of alginic acid to planktonic cell suspensions resulted in a slight increase in resistance to povidone-iodine, suggesting some neutralizing interaction. However, the iodine demands created by biofilm and planktonic samples of equivalent biomass were not significantly different and, therefore, do not explain the contrast in resistance observed between biofilm and planktonic samples. Examination of the relationship between cell death and biomass detachment from the glycocalyx matrix revealed that most cell death occurred in the fraction of biomass that detached from a biofilm during treatment. The overall rate of iodine diffusion through biofilms was not different from that of planktonic cells collected on a polycarbonate membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

The uptake and release of molecular iodine by the skin: chemical and bactericidal evidence of residual effects caused by povidone-iodine preparations.

The residual effect of iodine-based disinfectants is caused by a dynamic back-diffusion which is the reverse of the absorption occurring during application. A very sensitive photometric method was used to measure the iodine flux of the back-diffusion after treating the skin with povidone-iodine preparations and Lugol's solution. After removal of the preparation the intensity of the iodine flux decreases with time and correlates with the amount of iodine being resorbed. The latter depends on the concentration of free molecular iodine of the preparation, the contact time and the thickness of the horny layer of the treated skin. With Lugol's solution (approximately 170 ppm free molecular iodine) iodine flux could be observed 12-24 h after an application of 20-60s, while with low-level povidone-iodine preparations (0.5-20 ppm free iodine) the measurable flux lasted only 0.5-1 h after an application time of 3 min. The bactericidal activity of the back-diffusing iodine from skin previously treated with a commercial povidone-iodine preparation was assayed by using an inoculation with Micrococcus luteus. This showed a logarithmic reduction of 0.4 in bacterial concentration. Since the skin was washed with soap for 1 min after application this bactericidal action reflected the residual effect of the back-diffusing iodine.

Uptake of tyramine cellobiose by rat liver.

The uptake of 125I-tyramine cellobiose (TC) by isolated rat hepatocytes and by total rat liver is markedly higher than that of 14C-sucrose and 125I-PVP, suggesting that TC does not enter the cells by fluid phase endocytosis. The distribution of radioactivity after differential centrifugation shows that the compound is shared out amongst sedimentable structures and unsedimentable fraction. Analysis by isopycnic centrifugation indicates that quickly after its penetration into the cells, most of sedimentable 125I-TC is associated with lysosomes. Such an intracellular localization is confirmed by the distributions observed after free flow electrophoresis and by the fact that radioactivity and cathepsin C, a lysosomal hydrolase, are simultaneously released from a mitochondrial fraction treated with glycyl-L-phenylalanine-2-naphthylamide. Pretreatment of the rats with chloroquine, an acidotropic drug that accumulates in lysosomes, prevents to some extent the entry of 125I-TC into these organelles. Experiments performed with purified lysosomes show that 14C-sucrose does not cross the lysosomal membrane when 125I-TC accumulates linearly with time in the fractions. These results are explained by supposing that the linkage of tyramine to cellobiose allow the disaccharide to diffuse through the plasma and the lysosome membranes, and that the accumulation of the molecule in these organelles results from its weak basic properties. 125I-TC could be an interesting molecule with which to study acidotropism in the whole animal and in isolated and cultured cells.

The effects of ophthalmic solutions on the transmission of light through hydrogel lenses.

We incubated ten different hydrogel lens materials in nine different artificial tear preparations and in cromolyn sodium (Opticrom) 4% at 35 degrees C for a period of 6 months. The subsequent ability of these hydrogel materials to transmit visible light was analyzed spectrophotometrically as a measure of each solution's compatibility with the different hydrogel materials. Ultra Tears solution was found to be significantly incompatible with four of the hydrogel materials: tetrafilcon A, deltafilcon A, phemfilcon A, and polymacon. Seven other solution/hydrogel combinations had relatively high absorbance readings that were not statistically significant. These combinations should probably be avoided. Cromolyn sodium 4% was found to be compatible with all hydrogel lens materials tested, as were the majority of artificial tear solution/hydrogel combinations. We believe that the use of the compatible solution/hydrogel combinations should produce no alteration in the ability of the hydrogel lens to transmit visible light (400-700 nm).

[Thyroid function disturbances in an infant following maternal topical use of polydine].

A male infant who had symptoms of transient sinus tachycardia and increased concentrations of blood total and free T4 is reported. The mother had used Polydine (P; povidone iodine) for vaginal douching during pregnancy and during the first few weeks after delivery, during which time the infant was fed mother's milk only. Follow-up showed transient elevation of TSH levels in the infant, but with no signs of hypothyroidism. 2 months after the mother stopped using P, the infant's functions had become normal. P should not be used in the perinatal period.

Effect of feeding 5 per cent glucose solution or milk replacer to newborn piglets on intestinal permeability to macromolecules.

Newborn piglets were fed either a 5 per cent glucose/electrolyte solution or a commercial milk replacer for 24 or 36 hours before they were given colostrum, or they were given colostrum after birth. The effects of these treatments on their ability to absorb macromolecules was assessed by measuring the uptake of 125I-polyvinylpyrrolidone (125I-PVP) and the increases in the concentrations of total proteins and immunoglobulins in serum. The piglets which received colostrum at birth absorbed 50 per cent of a test dose of 125I-PVP within six hours, and there was a rapid increase in the concentration of immunoglobulins in their blood. The piglets which received the 5 per cent glucose/electrolyte solution absorbed 40 per cent of the test dose of 125I-PVP administered 24 or 36 hours after birth and nearly normal quantities of immunoglobulins, but the piglets given the milk replacer absorbed only 10 per cent of the test dose of 125I-PVP, and virtually no immunoglobulins.

Intestinal permeability to macromolecules during colibacillosis in piglets.

Intestinal macromolecular permeability to macromolecules was determined in a group of specific pathogen free piglets before and after they were infected experimentally with Escherichia coli. Six hours after the infection all piglets developed a profuse diarrhoea. The urea and total protein concentrations in the serum increased markedly after the onset of diarrhoea. Haemoglobin concentration and PCV decreased steadily during the experiment but blood glucose concentration and lipid composition of the faeces did not change. No structural abnormalities in the jejunal and ileal mucosa were seen. No uptake of macromolecules (40,000 KDa) was found suggesting that molecules with a molecular weight of 40,000 or more do not play a role in the persistent diarrhoea sometimes seen in piglets after colibacillosis.

Chemical and microbiologic characteristics and toxicity of povidone-iodine solutions.

The chemical, microbiologic, and toxic characteristics of povidone-iodine solution, a commonly used antiseptic agent, are addressed in a collective review of relevant works published from 1956 to the present. Interactions of this agent with the thyroid gland and the kidneys and its toxicity at the cellular and systemic level are discussed.

Antibody induced internalization of acetylcholine nicotinic receptor: kinetics, mechanism and selectivity.

The loss from the cell surface of cholinergic nicotinic receptors induced by exposure to antireceptor antibodies, and the mechanism of this loss has been studied in the BC3H-1 cell line. The maximal effect, i.e. 50% loss of receptors, was observed after 30 min. Receptor loss was due to internalization, which was not accompanied by a detectable increase in fluid phase endocytosis nor by changes in the number and distribution of intramembrane particles (IMP) revealed by freeze-fracture of the plasmalemma. The internalization was specific since the concentration of other receptors exposed at the surface of BC3H-1 cells (alpha and beta adrenergic receptors) was not affected by anticholinergic antibodies. It was temperature-dependent, independent of external calcium, but was blocked by trifluoperazine (TFP), a calmodulin antagonist. The rate of antibodies-induced receptor internalization was much more rapid than that of degradation and furthermore low concentrations of antibodies increased receptor internalization but did not increase receptor degradation. Our findings may be relevant to the clarification of the mechanism of Ab-induced alteration in autoimmune diseases, and in particular in myasthenia gravis.

The influence of povidone-iodine treatment on thyroid hormones in severe burns.

Average iodine serum levels of 2.5 mg/100 ml were obtained in 10 patients with an average burn area of 50% and treated with povidone-iodine. Simultaneous measurements of the thyroid hormones failed to reveal any significant impairment of thyroid function apart from depressed T3 coupled with increased reverse T3. Similar findings were obtained with a control group of 10 multiply-injured patients. If renal function is unimpaired the resorbed iodine is quickly excreted. No clinical signs of iodine intoxication were observed.

Povidone-iodine in the treatment of burn patients.

The improvement in infusion therapy of burn patients in the last decades has led to a marked reduction of the early mortality rate and to an increase in the importance of severe wound infection and septicaemia. For the control of infection, detailed bacteriological monitoring is recommended. The main therapeutic fields for prevention of infection are: immunotherapy, antisepsis, aseptic techniques, and rapid restoration of the destroyed body surface. The most important part of antisepsis in burns is topical treatment. The good bacteriological and clinical results with povidone-iodine (PVP-I), in combination with open treatment are described. A possible disadvantage of this therapy was the extensive iodine resorption. However, no disorders of thyroid function were revealed, and the TRH test indicated no abnormal reactions of the hypothalamus-pituitary axis. The high serum and urine iodine levels returned rapidly to normal after discontinuing the PVP-I application.

Comparison of blood serum iodine levels with use of Iodoplex and povidone iodine ointment.

Concentrations of iodine were assayed in burn patients, who were covered with Iodoplex ointment up to 30% of their body surface. The iodine levels in the serum were found to be in linear proportion to the area treated with an increase of 30 micrograms iodine per 100 ml of serum for 1% of TBSA. The maximal levels were reached within 24 hours of applying the Iodoplex ointment and decreased quickly following its discontinuation. Concentrations of the iodine were much lower than those found after treatment with povidone iodine, a fact which indicates that using Iodoplex in second-degree burns and donor sites entails fewer possible complications due to high levels of iodine in the serum than with povidone iodine.

Degradation of insulin by human fibroblasts: effects of inhibitors of pinocytosis and lysosomal activity.

The role of the pinosome-lysosome pathway in the degradation of 125I-labelled bovine insulin by cultured human fibroblasts was examined by comparing the effects of various known inhibitors of pinocytosis and lysosomal degradation on the uptake and degradation of 125I-labelled polyvinylpyrrolidone, formaldehyde-denatured bovine serum albumin and bovine insulin by these cells. Fibroblasts incubated with polyvinylpyrrolidone steadily accumulate this substrate, whereas incubations with insulin or denatured albumin led to the progressive appearance in the culture medium of [125I]iodotyrosine. Inhibitors of pinocytosis (bacitracin, colchicine and monensin), metabolic inhibitors (2,4-dinitrophenol and NaF), lysosomotropic agents (chloroquine and NH4Cl) and an inhibitor of cysteine-proteinases (leupeptin) decreased the rate of uptake of polyvinylpyrrolidone and denatured albumin very similarly, but only bacitracin had an effect on the processing of insulin. Chloroquine, NH4Cl and leupeptin strongly inhibited the digestion of denatured albumin, but not of insulin. The different responses to the modifiers, with polyvinylpyrrolidone and denatured albumin on the one hand and insulin on the other, suggest that insulin degradation can occur by a non-lysosomal pathway. The very strong inhibitory effect of bacitracin on insulin processing by fibroblasts may point to an important role of plasma membrane proteinases in insulin degradation.

[Iodine resorption from PVP-iodine preparations after their use in humans]. / Resorption von Jod aus PVP-Jod-Präparaten nach Anwendung am Menschen.

The absorption of iodine from iodine-containing PVP preparations and the possibility of iodide being split off from the organic compound were tested in subjects with normal thyroid function after they had used PVP-iodine as mouth-antiseptic (15 subjects), vaginal gel (20 subjects) or liquid soap (20 subjects). Serum I-, T3, T4, TSH and urinary iodide excretion were measured, as an index of thyroid function, before and after the PVP application. Increase in iodine supply was up to 2 mg daily in the test subjects. The overwhelming proportion of the absorbed iodine (greater than 75%) was as organically bound iodine. In none of the subjects was there evidence of developing hyper- or hypothyroidism as a result of the additional iodine supply. Approximate values for the biological half-life and the distribution volume of total iodine in the body were also obtained.

Changes in thyroid function and serum iodine levels after prepartum use of a povidone-iodine vaginal lubricant.

To determine if application of iodide to vaginal mucosa of pregnant women results in significant iodide absorption or changes in thyroid function, we studied 18 intrapartum women for whose examinations during labor povidone-iodine gel was used as a lubricant and 16 for whose examinations an iodine-free lubricant was used. Both serum inorganic iodine and total serum iodine increased significantly (p less than 0.001) after iodide exposure and fell (p = 0.003) to near baseline within two days. In both groups, serum thyroxine and triiodothyronine fell during labor and delivery; differences between groups were not significant. In the iodine-treated group, however, there was a significant increase in thyroid-stimulating hormone at two days postpartum (p less than 0.001). Iodide applied to vaginal mucosa of pregnant women is absorbed and affects the maternal pituitary-thyroid axis.