Effects of glutaraldehyde and povidone-iodine on apoptosis of grass carp liver and hepatocytes.

Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.

Impact of small fractions of abnormal erythrocytes on blood rheology.

Red blood cell (RBC) populations are inherently heterogeneous, given mature RBC lack the transcriptional machinery to re-synthesize proteins affected during in vivo aging. Clearance of older, less functional cells thus aids in maintaining consistent hemorheological properties. Scenarios occur, however, where portions of mechanically impaired RBC are re-introduced into blood (e.g., damaged from circulatory support, blood transfusion) and may alter whole blood fluid behavior. Given such perturbations are associated with poor clinical outcomes, determining the tolerable level of abnormal RBC in blood is valuable. Thus, the current study aimed to define the critical threshold of blood fluid properties to re-infused physically-impaired RBC. Cell mechanics of RBC were impaired through membrane cross-linking (glutaraldehyde) or intracellular oxidation (phenazine methosulfate). Mechanically impaired RBC were progressively re-introduced into the native cell population. Negative alterations of cellular deformability and high shear blood viscosity were observed following additions of only 1-5% rigidified RBC. Low-shear blood viscosity was conversely decreased following addition of glutaraldehyde-treated cells; high-resolution microscopy of these mixed cell populations revealed decreased capacity to form reversible aggregates and decreased aggregate size. Mixed RBC populations, when exposed to supraphysiological shear, presented with compounded mechanical impairment. Collectively, key determinants of blood flow behavior are sensitive to mechanical perturbations in RBC, even when only 1-5% of the cell population is affected. Given this fraction is well-below the volume of rigidified RBC introduced during circulatory support or transfusion practice, it is plausible that some adverse events following surgery and/or transfusion may be related to impaired blood fluidity.

Subacute Pulmonary Toxicity of Glutaraldehyde Aerosols in a Human In Vitro Airway Tissue Model.

Glutaraldehyde (GA) has been cleared by the Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) as a high-level disinfectant for disinfecting heat-sensitive medical equipment in hospitals and healthcare facilities. Inhalation exposure to GA is known to cause respiratory irritation and sensitization in animals and humans. To reproduce some of the known in vivo effects elicited by GA, we used a liquid aerosol exposure system and evaluated the tissue responses in a human in vitro airway epithelial tissue model. The cultures were treated at the air interface with various concentrations of GA aerosols on five consecutive days and changes in tissue function and structure were evaluated at select timepoints during the treatment phase and after a 7-day recovery period. Exposure to GA aerosols caused oxidative stress, inhibition of ciliary beating frequency, aberrant mucin production, and disturbance of cytokine and matrix metalloproteinase secretion, as well as morphological transformation. Some effects, such as those on goblet cells and ciliated cells, persisted following the 7-day recovery period. Of note, the functional and structural disturbances observed in GA-treated cultures resemble those found in ortho-phthaldehyde (OPA)-treated cultures. Furthermore, our in vitro findings on GA toxicity partially and qualitatively mimicked those reported in the animal and human survey studies. Taken together, observations from this study demonstrate that the human air-liquid-interface (ALI) airway tissue model, integrated with an in vitro exposure system that simulates human inhalation exposure, could be used for in vitro-based human hazard identification and the risk characterization of aerosolized chemicals.

Glutaraldehyde Cross-Linking of Oligolysines Coating DNA Origami Greatly Reduces Susceptibility to Nuclease Degradation.

DNA nanostructures (DNs) have garnered a large amount of interest as a potential therapeutic modality. However, DNs are prone to nuclease-mediated degradation and are unstable in low Mg2+ conditions; this greatly limits their utility in physiological settings. Previously, PEGylated oligolysines were found to protect DNs against low-salt denaturation and to increase nuclease resistance by up to ∼400-fold. Here we demonstrate that glutaraldehyde cross-linking of PEGylated oligolysine-coated DNs extends survival by up to another ∼250-fold to >48 h during incubation with 2600 times the physiological concentration of DNase I. DNA origami with cross-linked oligolysine coats are non-toxic and are internalized into cells more readily than non-cross-linked origami. Our strategy provides an off-the-shelf and generalizable method for protecting DNs in vivo.

Multimodal detection and analysis of a new type of advanced Heinz body-like aggregate (AHBA) and cytoskeleton deformation in human RBCs.

A new type of aggregate, formed in human red blood cells (RBCs) in response to glutaraldehyde treatment, was discovered and analyzed with the classical and advanced biomolecular imaging techniques. Advanced Heinz body-like aggregates (AHBA) formed in a single human RBC are characterized by a higher level of hemoglobin (Hb) degradation compared to typical Heinz bodies, which consist of hemichromes. The complete destruction of the porphyrin structure of Hb and the aggregation of the degraded proteins in the presence of Fe3+ ions are observed. The presence of such aggregated, highly degraded proteins inside RBCs, without cell membrane destruction, has been never reported before. For the first time the spatial differentiation of two kinds of protein mixtures inside a single RBC, with different phenylalanine (Phe) conformations, is visualized. The non-resonant Raman spectra of altered RBCs with AHBA are characterized by the presence of a strong band located at 1037 cm-1, which confirms that glutaraldehyde interacts strongly with Phe. The shape-shifting of RBCs from a biconcave disk to a spherical structure and sinking of AHBA to the bottom of the cell are observed. Results reveal that the presence of AHBA should be considered when fixing RBCs and indicate the analytical potential of Raman spectroscopy, atomic force microscopy and scanning near-field optical microscopy in AHBA detection and analysis.

Evaluation of the respiratory tract toxicity of ortho-phthalaldehyde, a proposed alternative for the chemical disinfectant glutaraldehyde.

ortho-Phthalaldehyde (OPA) is a high-level chemical disinfectant that is commonly used for chemical sterilization of dental and medical instruments as an alternative to glutaraldehyde, a known skin and respiratory sensitizer. Concern for safe levels of human exposure remains due to a lack of toxicity data as well as human case reports of skin and respiratory sensitization following OPA exposure. The present study evaluated the inhalational toxicity of OPA in Harlan Sprague-Dawley rats and B6C3F1/N mice. Groups of 10 male and female rats and mice were exposed to OPA by whole-body inhalation for 3 months at concentrations of 0 (control), 0.44, 0.88, 1.75, 3.5, or 7.0 ppm. Rats and mice developed a spectrum of lesions at sites of contact throughout the respiratory tract (nose, larynx, trachea, lung), as well as in the skin and eye, consistent with a severe irritant response. In general, histologic lesions (necrosis, inflammation, regeneration, hyperplasia and metaplasia) occurred at deeper sites within the respiratory tract with increasing exposure concentration. As a first site of contact, the nose exhibited the greatest response to OPA exposure and resulted in an increased incidence, severity and variety of lesions compared to a previous study of glutaraldehyde exposure at similar exposure concentrations. This increased response in the nasal cavity, combined with extensive lesions throughout the respiratory tract, provides concern for use of OPA as a replacement for glutaraldehyde as a high-level disinfectant.

Effects of Wastewater from Oil Exploration on Soil Mesofauna.

Wastewater from oil exploration may contain substances that can alter the diversity of soil organisms. This study evaluated whether produced water treated by filtration or reverse osmosis and glutaraldehyde from reverse osmosis treatments negatively affected the mesofauna in an irrigated area. In the field, irrigation with produced water treated by reverse osmosis and filtration influenced Hymenoptera and Cosmochthonius sp., while Entomobryomorpha springtails were affected only by the reverse osmosis water. In the ecotoxicological tests, reproduction in the springtail Folsomia candida was inhibited by the reverse osmosis treatment, while reproduction in the earthworm Enchytraeus crypticus was affected by both water treatments. Although glutaraldehyde did not affect the survival of F. candida, the reproduction was inhibited (EC50 = 44.4 mg/L). No adverse effect of glutaraldehyde was observed on reproduction or survival of E. crypticus. These results indicate that produced water, when used in irrigated agriculture, may affect soil functional mesofauna.

Assessing the impact of national level interventions on workplace respiratory disease in the UK: part 1--changes in workplace exposure legislation and market forces.

OBJECTIVE: The 2004 amendment to the Control of Substances Hazardous to Health 2002 regulations (COSHH 2004) introducing workplace exposure limits (WELs) was enacted in the UK in 2005. This study aimed to determine whether introducing this legislation coincided with a reduction in the incidence of work-related short latency respiratory disease (SLRD) attributed to the agents with a WEL. The second objective was to determine whether changes in legislation, WELs and market forces coincided with a reduction in the incidence of SLRD attributed to glutaraldehyde and latex. METHOD: Reports of SLRD made to the Surveillance of Work-related and Occupational Respiratory Disease scheme were used to estimate the change in incidence within reporters between two time periods (interrupted time series design) using a longitudinal, negative binomial regression model with ß distributed random effects. A statistical interaction term was included in the model to make comparisons between the groups defined by suspected causal agent and/or occupation, essentially comparing two interrupted time series. Time periods were defined prospectively representing the changes in legislation or market forces. RESULTS: The introduction of the COSHH 2004 legislation in the UK coincided with a significant reduction in reports of SLRD attributed to agents with a WEL relative to those without a WEL (ratio of incidence rate ratios: 0.70; 95% CI 0.52 to 0.93) and a significant reduction in SLRD attributed to glutaraldehyde in healthcare workers (0.20; 0.07 to 0.57) and latex in all workers (0.37; 0.16 to 0.85). CONCLUSIONS: These data are consistent with a beneficial effect of legislation aiming to reduce workplace exposures.

Potentiation of high hydrostatic pressure inactivation of Mycobacterium by combination with physical and chemical conditions.

Mycobacterium abscessus is an important hospital-acquired pathogen involved in infections associated with medical, surgical, and biopharmaceutical materials. In this work, we investigated the pressure-induced inactivation of two strains [2544 and American Type Culture Collection (ATCC) 19977] of M. abscessus in combination with different temperatures and pH conditions. For strain 2544, exposure to 250 MPa for 90 min did not significantly inactivate the bacteria at 20 °C, whereas at -15 °C, there was complete inactivation. Exposure to 250 MPa at ≥60 °C caused rapid inactivation, with no viable bacteria after 45 min. With 45 min of exposure, there were no viable bacteria at any temperature when a higher pressure (350 MPa) was used. Extremes of pH (4 or 9) also markedly enhanced the pressure-induced inactivation of bacteria at 250 MPa, with complete inactivation after 45 min. In comparison, exposure of this strain to the disinfecting agent glutaraldehyde (0.5 %) resulted in total inactivation within 5 min. Strain 19977 was more sensitive to high pressure but less sensitive to glutaraldehyde than strain 2544. These results indicate that high hydrostatic pressure in combination with other physical parameters may be useful in reducing the mycobacterial contamination of medical materials and pharmaceuticals that are sensitive to autoclaving.

Mitigation of calcification and cytotoxicity of a glutaraldehyde-preserved bovine pericardial matrix: improved biocompatibility after extended implantation in the subcutaneous rat model.

BACKGROUND AND AIMS OF THE STUDY: Implanted non-crosslinked tissues suffer rapid degeneration, shrinkage and absorption, whereas standard crosslinked tissues cause local cytotoxicity and calcification. Both approaches diminish implant capacity for long-term function. The study aim was to examine the tissue-engineered characteristics (cytotoxicity, calcification potential, biocompatibility) of bovine pericardium, crosslinked with a low concentration of glutaraldehyde (GA) followed by ADAPT anti-mineralization, following prolonged implantation in a subcutaneous rat model. METHODS: Bovine pericardium was decellularized with Triton X-100, deoxycholate, IgePal CA-630, and nucleases. The resulting matrices were allocated to: group I (control, n=10), crosslinked in 0.2% polymeric GA; and group II (treatment, n=10), crosslinked in 0.05% monomeric GA + ADAPT. Cytotoxicity was determined by in vitro cell seeding with human fibroblasts, and quantified using an Alamar Blue assay. The matrices were then implanted in a subcutaneous rat model and retrieved after extended implantation times (26 and 52 weeks). This was followed by further histology, immunohistochemical staining, and measurement of calcium deposition. RESULTS: Complete acellularity and biostability were significantly (p < 0.01) achieved in group II. Inflammatory responses were reduced and beneficial host cell infiltration with neocapillary formation was limited to group II. Fibroblast infiltration was significantly increased from six to 12 months' implantation time. Only group II tested positive for Factor VIII and vimentin. After 52 weeks, extractable calcium levels were significantly (p < 0.001) reduced in group II (2.56 +/- 0.22 microg Ca/mg tissue) compared to group I (136.02 +/- 0.39 microg Ca/mg tissue). CONCLUSION: Acellular bovine pericardium, when crosslinked with a low concentration of GA and treated with ADAPT, retains and improves its integrity with a low immunoreactivity over a prolonged period. Host cell infiltration is also optimized over time. The maintenance of reduced calcification levels in group II suggests that such a biomaterial might have an advanced long-term in vivo potential.

Environmental electroactive consortia as reusable biosensing element for freshwater toxicity monitoring.

The development of tools to monitor water quality is mandatory in a scenario where clean water resources are decreasing. Here, the biosensing capability of an electroactive river sediment consortium was tested towards three model contaminants (glutaraldehyde, nickel(II) and chromium(III)). The proposed biosensor is a small membrane-less single chamber Microbial Fuel Cell (MFC), fabricated by 3D printing. Its semi-continuous mode of operation resulted in long-term current profile stability and reproducibility. A linear trend of response was obtained for glutaraldehyde in a concentration range of 5-1000 ppm. After the recovery of the electroactive consortium activity, the MFC-based biosensors were shown to be sensitive towards Ni(II) and Cr(III), at concentrations above 2 mg L-1. To effectively analyze biosensor response, a novel algorithm was proposed, offering advantages for the realization of energy-saving protocols for MFC-biosensor data transmission. Implementation of the device and method, from laboratory test to real environment, can offer a low cost in situ system for detection of water contaminants.

Evaluation of the Effect of Crosslinking Method of Poly(Vinyl Alcohol) Hydrogels on Thrombogenicity.

PURPOSE: Crosslinked poly(vinyl alcohol) (PVA) is a biomaterial that can be used for multiple cardiovascular applications. The success of implanted biomaterials is contingent on the properties of the material. A crucial consideration for blood-contacting devices is their potential to incite thrombus formation, which is dependent on the material surface properties. The goal of this study was to quantify the effect of different crosslinking methods of PVA hydrogels on in vitro thrombogenicity. METHODS: PVA was manufactured using three different crosslinking methods: 30% sodium trimetaphosphate (STMP), three 24 h freeze-thaw cycles (FT), and 2% glutaraldehyde-crosslinked (GA) to produce STMP-PVA, FT-PVA and GA-PVA, respectively. Expanded polytetrafluoroethylene (ePTFE) was used as a clinical control. As markers of thrombus formation, the degree of coagulation factor (F) XII activation, fibrin formation, and platelet adhesion were measured. RESULTS: The GA-PVA material increased FXII activation in the presence of cofactors compared to vehicle and increase platelet adhesion compared to other PVA surfaces. The STMP-PVA and FT-PVA materials had equivalent degrees of FXII activation, fibrin formation and platelet adhesion. CONCLUSION: This work supports crosslinker dependent thrombogenicity of PVA hydrogels and advances our understanding of how the manufacturing of a PVA hydrogel affects its hemocompatibility.

Toxicological aspects of increased use of surface and hand disinfectants in Croatia during the COVID-19 pandemic: a preliminary report.

All COVID-19 prevention strategies include regular use of surface disinfectants and hand sanitisers. As these measures took hold in Croatia, the Croatian Poison Control Centre started receiving phone calls from the general public and healthcare workers, which prompted us to investigate whether the risk of suspected/symptomatic poisonings with disinfectants and sanitisers really increased. To that end we compared their frequency and characteristics in the first half of 2019 and 2020. Cases of exposures to disinfectants doubled in the first half of 2020 (41 vs 21 cases in 2019), and exposure to sanitisers increased about nine times (46 vs 5 cases in 2019). In 2020, the most common ingredients of disinfectants and sanitisers involved in poisoning incidents were hypochlorite/glutaraldehyde, and ethanol/isopropyl alcohol, respectively. Exposures to disinfectants were recorded mostly in adults (56 %) as accidental (78 %) through ingestion or inhalation (86 %). Fortunately, most callers were asymptomatic (people called for advice because they were concerned), but nearly half reported mild gastrointestinal or respiratory irritation, and in one case severe symptoms were reported (gastrointestinal corrosive injury). Reports of exposure to hand sanitisers highlighted preschool children as the most vulnerable group. Accidental exposure through ingestion dominated, but, again, only mild symptoms (gastrointestinal or eye irritation) developed in one third of the cases. These preliminary findings, however limited, confirm that increased availability and use of disinfectants and sanitisers significantly increased the risk of poisoning, particularly in preschool children through accidental ingestion of hand sanitisers. We therefore believe that epidemiological recommendations for COVID-19 prevention should include warnings informing the general public of the risks of poisoning with surface and hand disinfectants in particular.

Occupational asthma and the paper recycling industry.

BACKGROUND: Occupational disease linked to the paper recycling industry has not been well documented. No previously confirmed formal diagnosis of occupational asthma (OA) caused by hydroxylamine has been made. METHODS: We have assessed and performed occupational assessment of eight workers involved in this industry. Two of these were later diagnosed with OA and are reported here. RESULTS: Both workers developed their respiratory symptoms within 2 years of the first use of the chemical hydroxylamine as part of the 'de-inking' process. Hydroxylamine was used as a substitute for glutaraldehyde on risk grounds, although no prior cases of OA had been found. The two workers had worked at the same plant for 11 and 20 years, respectively. Both gave histories of work-related wheeze, shortness of breath and cough. Both cases performed OASYS peak flow records over a 3-week period and had OASYS II index of 2.85 and 2.67, respectively. Both were redeployed on site to non-exposed areas and subsequently demonstrated improvement in bronchial reactivity. Case 2 subsequently consented to and underwent a blinded, placebo-controlled occupational challenge using hydroxylamine demonstrating a significant isolated late asthmatic response. CONCLUSIONS: We believe that these are the first two confirmed cases of OA caused by hydroxylamine in the paper recycling industry.

The benzene metabolite trans,trans-muconaldehyde blocks gap junction intercellular communication by cross-linking connexin43.

Benzene is used at large volumes in many different human activities. Hematotoxicity and cancer-causation as a result of benzene exposure was recognized many years ago, but the mechanisms involved remain unclear. Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to both cancer induction and interference with normal hematopoietic development. We have previously suggested that inhibition of GJIC may play a role in benzene toxicity since benzene metabolites were found to block GJIC, the ring-opened trans,trans-muconaldehyde (MUC) being the most potent metabolite. In the present work we have studied the molecular mechanisms underlying the MUC-induced inhibition of gap junctional communication. We show that MUC induces cross-linking of the gap junction protein connexin43 and that this is likely to be responsible for the induced inhibition of GJIC, as well as the loss of connexin43 observed in Western blots. We also show that glutaraldehyde possesses similar effects as MUC, and we compare the effects to that of formaldehyde. The fact that glutaraldehyde and formaldehyde have been associated with induction of leukemia as well as disturbance of hematopoiesis, strengthens the possible link between the effect of MUC on gap junctions, and the toxic effects of benzene.

Pre-irradiation exposure of peripheral blood lymphocytes to glutaraldehyde induces radiosensitization by increasing the initial yield of radiation-induced chromosomal aberrations.

Glutaraldehyde (GA) is a high production volume chemical that is very reactive with a wide spectrum of medical, scientific and industrial applications. Since human exposure in anthropogenic and occupational environment occurs frequently, GA has been extensively tested for genotoxic activity in vitro and in vivo. However, there are conflicting results in the literature and there is a lack of information concerning the combined effects of exposure to both GA and ionizing radiation in human cells. In the present study, the results obtained using conventional cytogenetic analysis do not suggest a statistically significant clastogenic or genotoxic activity of GA when concentrations in the range of 10(-6) to 10(-2) mM were applied. However, a 24-h pre-irradiation exposure of human peripheral blood lymphocytes (PBLs) to non-genotoxic doses of GA showed a statistically significant (P > 0.05) increase in chromosomal radiosensitivity. The observed increase may be an effect of GA-induced alterations in the cell-cycle and feedback control mechanisms during the cell-cycle transition points or it may be a consequence of an effect of GA either on the DNA repair capacity of the cells after irradiation or on the initial induction of radiation-induced chromosomal damage. To elucidate the mechanism underlying the obtained radiosensitization, conventional cytogenetics, the G2 chromosomal radiosensitivity assay and premature chromosome condensation methodologies were applied. The results support the hypothesis that pre-irradiation exposure of PBLs to GA induces radiosensitization by increasing the initial yield of chromosomal aberrations following irradiation.

The genotoxic potential of glutaraldehyde in mammalian cells in vitro in comparison with formaldehyde.

Glutaraldehyde (GA) induces DNA-protein crosslinks (DPX), but conflicting results have been reported with regard to other genotoxic and mutagenic effects in mammalian cells in vitro. We, therefore, characterized the genotoxic and mutagenic potential of GA in V79 cells. Using the alkaline comet assay we demonstrated the induction of DPX by GA (reduction of gamma ray-induced DNA migration) at a concentration of 10 microM and above. The standard comet assay did not reveal a significant DNA strand-breaking activity of GA. Cross-linking concentrations of GA were also cytotoxic, i.e. inhibited cell growth of treated V79 cultures. Interestingly, a small but statistically significant increase in sister chromatid exchange (SCE) and micronuclei (MN) was already measured at lower concentrations (2 and 5 microM). FISH analysis revealed that the majority of GA-induced MN was due to chromosome breaks. We also compared the genotoxic activity of GA to that of formaldehyde (FA). Similar to GA, FA-induced DPX, SCE and MN, but distinct differences exist with regard to the sensitivity of the endpoints and the relationship between genotoxicity and cytotoxicity. However, the differences in genotoxicity cannot readily explain the different carcinogenic activities of the two compounds.

Octanediol treatment of glutaraldehyde fixed bovine pericardium: evidence of anticalcification efficacy in the subcutaneous rat model.

OBJECTIVE: Anticalcification strategies of glutaraldehyde-fixed xenograft tissue aim to extract lipids or to neutralize toxic aldehyde residuals. The purpose of this study was to evaluate the efficacy of octanediol compared to standard treatments of glutaraldehyde-fixed bovine pericardium in the subdermal rat model. Octanediol treatment is an ethanolic solution (40%) containing a long chain aliphatic alcohol (5% 1,2-octanediol) that removes lipids without diminishing the stability of collagen. METHODS: Octanediol and standard glutaraldehyde fixed bovine pericardium were both implanted in 24 Sprague-Dawley rats, explanted after 30-75 days (12 animals each) and submitted to X-ray (score 0-4), histology, electron microscopy and elemental analysis by spectroscopy (Ca and P content). Unimplanted octanediol and standard glutaraldehyde fixed pericardium served as control. RESULTS: At 30 days octanediol-treated pericardium showed calcium content of 0.20+/-0.1 vs 20.07+/-36.79 mg/g dry weight for standard pericardium. The difference was also evident at 75 days: calcium content of 2.36+/-7.38 mg/g dry weight for octanediol vs 165.61+/-23.35 mg/g dry weight for standard (p<0.0001). Differences were also detected at X-ray (mean score 0.7+/-0.6 octanediol vs 3.8+/-0.4 standard at 75 days). Equally, mean P content was 11.69+/-21.33 mg/g dry weight for standard vs 0.60+/-1.45 mg/g dry weight for octanediol samples at 30 days, and 90.90+/-12.61 mg/g dry weight for standard vs 1.42+/-4.34 mg/g dry weight for octanediol at 75 days (p<0.0001). At electron microscopy collagen appeared well preserved regardless of the type of treatment; in octanediol treated pericardium cell membranes almost disappeared and only few profiles of endoplasmic reticulum and rare mitochondria were visible. CONCLUSIONS: Treatment with octanediol strongly prevents calcification of glutaraldehyde fixed bovine pericardium in rat subdermal model, even in the long-term. Evidence of octanediol efficacy may entail important implications for new generation bioprosthetic valves.

Joint-action ecotoxicity of binary mixtures of glutaraldehyde and surfactants used in hospitals: use of the Toxicity Index model and isoblogram representation.

Glutaraldehyde and surfactants are widely used in hospitals and these substances have been detected in urban sewer networks and in surface water. The ecotoxicity of hospital wastewater has been reported in the literature, which identifies detergents and disinfectants as the main causes of toxicity. The aim of this study was to determine the combined effects of glutaraldehyde and three surfactants on Daphnia magna. Three binary mixtures were studied in five predefined ratios: glutaraldehyde with sodium dodecyl sulfate (SDS--an anionic surfactant), then Triton X-100 (TX-100--a nonionic surfactant), and finally cetyltrimethyl ammonium bromide (CATB--a cationic surfactant). The joint-action toxicity of binary mixtures was studied by acute bioassays on Daphnia magna. Two complementary methods were used to evaluate the combined effects of the mixtures on the selected organism: the Toxicity Index model (a quantitative method for analyzing the combined effects of binary and multiple mixtures) and the isobole representation (a qualitative method that has the advantage of being illustrative). An additive effect was observed between glutaraldehyde and surfactants for all the ratios studied and additive action could be an efficient method for evaluating the effect of hospital wastewater on Daphnia magna.