Protective Effects of [6]-Gingerol Against Chemical Carcinogens: Mechanistic Insights.

[6]-Gingerol from ginger has received considerable attention as a potential cancer therapeutic agent because of its chemopreventive and chemotherapeutic effects, as well as its safety. In the current study, we examined [6]-gingerol as a natural scavenger of nine ultimate chemical carcinogens to which we are frequently exposed: glycidamide, styrene oxide, aflatoxin B1 exo-8,9-epoxide, ß-propiolactone, ethylene oxide, propylene oxide, 2-cyanoethylene oxide, chloroethylene oxide, and vinyl carbamate epoxide. To evaluate [6]-gingerol efficacy, we expanded our research with the examination of glutathione-the strongest natural scavenger in human cells. The corresponding activation free energies were calculated using Hartree-Fock method with three flexible basis sets and two implicit solvation models. According to our results, [6]-gingerol proves to be an extremely effective scavenger of chemical carcinogens of the epoxy type. On the other hand, with the exception of aflatoxin B1 exo-8,9-epoxide, glutathione represents a relatively poor scavenger, whose efficacy could be augmented by [6]-gingerol. Moreover, our quantum mechanical study of the alkylation reactions of chemical carcinogens with [6]-gingerol and glutathione provide valuable insights in the reaction mechanisms and the geometries of the corresponding transition states. Therefore, we strongly believe that our research forms a solid basis for further computational, experimental and clinical studies of anticarcinogenic properties of [6]-gingerol as well as for the development of novel chemoprophylactic dietary supplements. Finally, the obtained results also point to the applicability of quantum chemical methods to studies of alkylation reactions related to chemical carcinogenesis.

The effects of NRF2 modulation on the initiation and progression of chemically and genetically induced lung cancer.

Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progression are needed to identify which therapeutic avenue-activation or inhibition-is appropriate in a given context. Moreover, while numerous reports confirm the protective effect of NRF2 activation against chemical carcinogenesis little is known of its role in cancer arising from spontaneous mutations. Here, we tested the effects of NRF2 modulation (activation by sulforaphane or inhibition by brusatol) in lung carcinogenesis using a chemical (vinyl carbamate) model in A/J mice and a genetic (conditional KrasG12D oncogene expression, to simulate spontaneous oncogene mutation) model in C57BL/6J mice. Mice were treated with NRF2 modulators before carcinogen exposure or KrasG12D expression to test the role of NRF2 in cancer initiation, or treated after tumor development to test the role of NRF2 in cancer progression. Lung tissues were analyzed to determine tumor burden, as well as status of NRF2 and KRAS pathways. Additionally, proliferation, apoptosis, and oxidative DNA damage were assessed. Overall, NRF2 activation prevents initiation of chemically induced cancer, but promotes progression of pre-existing tumors regardless of chemical or genetic etiology. Once tumors are initiated, NRF2 inhibition is effective against the progression of chemically and spontaneously induced tumors. These results have important implications for NRF2-targeted cancer prevention and intervention strategies.

Bioinspired pH- and Temperature-Responsive Injectable Adhesive Hydrogels with Polyplexes Promotes Skin Wound Healing.

Despite great potential, the delivery of genetic materials into cells or tissues of interest remains challenging owing to their susceptibility to nuclease degradation, lack of permeability to the cell membrane, and short in vivo half-life, which severely restrict their widespread use in therapeutics. To surmount these shortcomings, we developed a bioinspired in situ-forming pH- and temperature-sensitive injectable hydrogel depot that could control the delivery of DNA-bearing polyplexes for versatile biomedical applications. A series of multiblock copolymer, comprised of water-soluble poly(ethylene glycol) (PEG) and pH- and temperature-responsive poly(sulfamethazine ester urethane) (PSMEU), has been synthesized as in situ-forming injectable hydrogelators. The free-flowing PEG-PSMEU copolymer sols at high pH and room temperature (pH 8.5, 23 °C) were transformed to stable gel at the body condition (pH 7.4, 37 °C). Physical and mechanical properties of hydrogels, including their degradation rate and viscosity, are elegantly controlled by varying the composition of urethane ester units. Subcutaneous administration of free-flowing PEG-PSMEU copolymer sols to the dorsal region of Sprague-Dawley rats instantly formed hydrogel depot. The degradation of the hydrogel depot was slow at the beginning and found to be bioresorbable after two months. Cationic protein or DNA-bearing polyplex-loaded PEG-PSMEU copolymer sols formed stable gel and controlled its release over 10 days in vivo. Owing to the presence of urethane linkages, the PEG-PSMEU possesses excellent adhesion strength to wide range of surfaces including glass, plastic, and fresh organs. More importantly, the hydrogels effectively adhered on human skin and peeled easily without eliciting an inflammatory response. Subcutaneous implantation of PEG-PSMEU copolymer sols effectively sealed the ruptured skin, which accelerated the wound healing process as observed by the skin appendage morphogenesis. The bioinspired in situ-forming pH- and temperature-sensitive injectable adhesive hydrogel may provide a promising platform for myriad biomedical applications as controlled delivery vehicle, adhesive, and tissue regeneration.

Synthesis, antiproliferative activity and molecular docking of thiocolchicine urethanes.

A number of naturally occurring compounds such as paclitaxel, vinblastine, combretastatin, and colchicine exert their therapeutic effect by changing the dynamics of tubulin and its polymer form, microtubules. The identification of tubulin as a potential target for anticancer drugs has led to extensive research followed by clinical development of numerous compounds from several families. In this paper we report on the design, synthesis and in vitro evaluation of a group of thiocolchicine derivatives, modified at ring-B, labelled here compounds 4-14. These compounds have been obtained in a simple reaction of 7-deacetyl-10-thiocolchicine 3 with eleven different alcohols in the presence of triphosgene. These novel agents have been checked for anti-proliferative activity against four human cancer cell lines and their mode of action has been confirmed as colchicine binding site inhibition (CBSI) using molecular docking. Molecular simulations provided rational tubulin binding models for the tested compounds. On the basis of in vitro tests, derivatives 4-8 and 14 demonstrated the highest potency against MCF-7, LoVo and A549 tumor cell lines (IC50 values = 0.009-0.014 µM). They were more potent and characterized by a higher selectivity index than several standard chemotherapeutics including cisplatin and doxorubicin as well as unmodified colchicine. Further, studies revealed that colchicine and its several derivatives arrested MCF-7 cells in mitosis, while its selected derivatives caused microtubule depolymerization.

Infectious agents after liver transplant: etiology, timeline and patients' cell-mediated immunity responses.

Infections continue to be one of the leading causes of morbidity and mortality in liver transplant recipients. We retrospectively reviewed the symptomatic infectious episodes that occurred during the first year post-transplant to determine time of onset, causative pathogens and cell-mediated immunity response patterns. Ninety-eight of the 202 (48.5%) recipients enrolled developed at least one infectious episode. The total number of infectious episodes was 135: 77 (57.1%) bacterial, 45 (33.3%) viral and 13 (9.6%) fungal. The most frequently isolated bacteria were Escherichia coli (21 isolates) and Klebsiella pneumoniae (19 isolates). Overall, extended-spectrum beta lactamase-producing and methicillin-resistant organisms were responsible for 29 (29/77; 37.7%) infectious episodes. Members of the herpes virus group, in particular cytomegalovirus (34/45 viral infections, 75.5%), were detected. Candida species (9 isolates) followed by Aspergillus species (4 isolates) were isolated. The majority of infections (63%) occurred during the early post-transplant phase (<1 month), whereas only 8/135 episodes (5.9%) were detected after the sixth month (late phase). Significantly lower median ImmuKnow® intracellular ATP values in patients who developed bacterial and fungal infections compared to infection-free patients were observed (P < 0.0001 and P = 0.0016, respectively), whereas patients who developed a viral infection had a median intracellular ATP level not statistically different compared to uninfected patients (P = 0.4). Our findings confirm that bacteria are responsible for the majority of symptomatic infections and occur more frequently during the first month post-transplant. The ImmuKnow® measurements can be a useful tool for identifying patients at high risk of developing infection, particularly of fungal and bacterial etiology.

Emulsion Inks for 3D Printing of High Porosity Materials.

Photocurable emulsion inks for use with solid freeform fabrication (SFF) to generate constructs with hierarchical porosity are presented. A high internal phase emulsion (HIPE) templating technique was utilized to prepare water-in-oil emulsions from a hydrophobic photopolymer, surfactant, and water. These HIPEs displayed strong shear thinning behavior that permitted layer-by-layer deposition into complex shapes and adequately high viscosity at low shear for shape retention after extrusion. Each layer was actively polymerized with an ultraviolet cure-on-dispense (CoD) technique and compositions with sufficient viscosity were able to produce tall, complex scaffolds with an internal lattice structure and microscale porosity. Evaluation of the rheological and cure properties indicated that the viscosity and cure rate both played an important role in print fidelity. These 3D printed polyHIPE constructs benefit from the tunable pore structure of emulsion templated material and the designed architecture of 3D printing. As such, these emulsion inks can be used to create ultra high porosity constructs with complex geometries and internal lattice structures not possible with traditional manufacturing techniques.

Nanotopography and plasma treatment: redesigning the surface for vascular graft endothelialisation.

INTRODUCTION: Vascular graft materials in clinical use, such as polytetrafluoroethylene (PTFE) and Dacron, do not endothelialise and have low patency rates. The importance of an endothelial cell layer on the luminal surface of a vascular graft is well-known with surface topography and chemistry playing an important role. The aim of this study was to investigate the potential of plasma treatment and topographical structures on the luminal graft surface to enhance the self-endothelialisation potential of a nanocomposite vascular graft. METHODS: POSS-PCU is a polycarbonate urea urethane (PCU) with a nanoparticle, polyhedral oligomeric silsesquioxane (POSS) incorporated within it. Planar, microgrooved, and nanopit patterned polymer films were fabricated using photolithography, electron beam lithography, reactive ion etching, and replication by solvent casting. Films were then exposed to oxygen plasma treatment at different powers for a fixed time (40 W, 60 W, 80 W/60 seconds). Effects of plasma treatment were assessed using scanning electron microscopy, atomic force microscopy and water contact angle analysis. Human umbilical vein endothelial cell (HUVEC) proliferation and morphology were characterised using immunostaining, live/dead staining, and Coomassie blue staining. RESULTS: Successful embossing of the micro- and nanostructures was confirmed. Oxygen plasma treatment of the different samples showed that increasing power significantly increased the hydrophilicity of the samples (p < .0001). Improved HUVEC adhesion was seen on plasma modified compared with untreated samples (p < .0001). Coomassie blue staining showed that after 5 days, cells started to form monolayers and live/dead staining showed the cells were viable. Immunostaining showed that HUVECs expressed nitric oxide synthase on all topographies with focal adhesions appearing more pronounced on nanopit surfaces, showing retention of morphology and function. CONCLUSION: These encouraging results indicate a future important role for plasma treatment and nanotopography in the development of endothelialised vascular grafts.

[THE 105-ANNIVERSARY OF THE DISCOVERY INTRAVENOUS ANESTHESIA].

The article shows the role off Jeremic Alexander in the discovery and development of the first methods of intravenous anesthesia in the world.

Function of the loading module in CorI and of the O-methyltransferase CorH in vinyl carbamate biosynthesis of the antibiotic corallopyronin A.

Corallopyronin A is a promising in vivo active antibiotic, currently undergoing preclinical evaluation. This myxobacterial compound interferes with a newly identified drug target site, i.e., the switch region of the bacterial DNA-dependent RNA-polymerase (RNAP). Since this target site differs from that of known RNAP inhibitors such as the rifamycins, corallopyronin A shows no cross-resistance with other antibacterial agents. Corallopyronin A is a polyketide synthase- and nonribosomal peptide synthetase-derived molecule whose structure and biosynthesis is distinguished by several peculiarities, such as the unusual vinyl carbamate functionality whose formation involves carbonic acid as an unprecedented C1-starter unit. Using in vitro experiments the nature of this starter molecule was revealed to be the methyl ester of carbonic acid. Biochemical investigations showed that methylation of carbonic acid is performed by the O-methyltransferase CorH. These experiments shed light on the biosynthesis of the Eastern chain of α-pyrone antibiotics such as corallopyronin A.

Resistance against bacterial leakage of four luting agents used for cementation of complete cast crowns.

PURPOSE: To assess the sealing properties of four luting materials used for cementation of full cast crowns. METHODS: 40 human premolars were prepared with a chamfer finish line. Stone dies were fabricated and copings were waxed, invested and cast in gold. Ten samples (n = 10) were randomly assigned to four groups. In two groups, resin modified glass-ionomer cements were used, ACTIVA BioACTIVE-CEMENT/BASE/LINER and FujiCem2; the third group received the self-adhesive resin cement Embrace WetBond, while the fourth group served as control with a zinc phosphate cement. After cementation, excess cement was removed followed by bench-set for 10 minutes. All samples were stored in water at 37 degrees C and subjected to thermal cycling (x2000 between 5 and 55 degrees C). Subsequently the occlusal surface was reduced exposing the dentin. After sterilization the specimens were subjected to bacterial microleakage with E. faecalis in a dual chamber apparatus for a period of 60 days. Bacterial leakage was checked daily. Data were analyzed using the Kaplan-Meyer survival test. Significant pairwise differences were analyzed using the Log Rank test and the Fishers' exact test at P < 0.05. RESULTS: ACTIVA BioACTIVE-CEMENT/BASE/LINER, FujiCem2 and Embrace WetBond showed the lowest microleakage scores and differed statistically significantly (P < 0.05) from zinc phosphate cement.

Beetroot red (betanin) inhibits vinyl carbamate- and benzo(a)pyrene-induced lung tumorigenesis through apoptosis.

Betanin, also called beetroot red, has been extensively used as a food colorant. In this study, the chemopreventive activity of betanin by oral consumption was investigated in two mouse lung tumor models. Vinyl carbamate (VC) and benzo(a)pyrene (B(a)P) were used to induce lung tumors, and female A/J mice were treated with betanin in drinking water. Betanin significantly decreased tumor multiplicity and tumor load induced by both carcinogens. Tumor multiplicity and tumor load were decreased by 20% and 39% in the VC lung model, and by 46% and 65% in the B(a)P lung model, respectively. Betanin reduced the number of CD31+ endothelial microvessels and increased the expression of caspase-3, suggesting that the lung tumor inhibitory effects were through induction of apoptosis and inhibition of angiogenesis. Betanin also induced apoptosis through activated caspase-3, -7, -9, and PARP in human lung cancer cell lines. Our data show that betanin significantly inhibits lung tumorigenesis in A/J mice and merits investigation as a chemopreventive agent for human lung cancer.

Anticandidal activity and biocompatibility of a rechargeable antifungal denture material.

OBJECTIVES: Candida-associated denture stomatitis is a recurrent and debilitating oral mucosal disease. Development of anticandidal denture materials represents a promising strategy to manage this condition. We have previously shown that miconazole incorporated in methacrylic acid (MAA) copolymerized diurethane dimethacrylate (UDMA) denture materials has long-term anticandidal activity. In this study, we examined the ability of culture medium conditioned with drug-free- or miconazole-MAA-UDMA discs to prevent Candida infection in an in vitro oral epithelial cell/Candida albicans coculture system. MATERIALS AND METHODS: Candida albicans (C. albicans)-induced OKF6/TERT-2 cell damage was quantified by the release of lactate dehydrogenase from epithelial cells, cytokine production was quantified using protein cytokine arrays, and the expression of C. albicans genes was measured by RT-qPCR. RESULTS: Candida albicans had limited growth with altered expression levels of secreted aspartyl proteinase-2 and -5 in culture medium conditioned by miconazole-MAA-UDMA discs. Significantly, the ability of C. albicans to induce oral epithelial cell damage and trigger epithelial proinflammatory cytokine production was also inhibited by miconazole disc conditioned media. CONCLUSION: Miconazole released from MAA-UDMA denture materials effectively prevents the development of candidal infection in an in vitro oral epithelial system. Further characterization of this drug-rechargeable denture material is warranted.

Investigations towards nano-hybrid resin-based composites.

OBJECTIVE: Clinical data indicate an increased trend in material fracture as reason for failure in composite restorations, questioning whether modern resin-based composites (RBCs) are able to fulfil the rising aesthetical demands and to provide at the same time a sufficient mechanical stability also in larger cavities. Nano-hybrid RBCs are promoted as materials with improved mechanical properties. The aim of this study was to analyse differences in mechanical properties within and between modern flowable and non-flowable nano-hybrid and micro-hybrid RBCs by measuring mechanical properties at macro- and micro-scale. METHODS: Thirty-four RBCs with traditional and new monomer formulation or photo-polymerization initiator technology-15 nano-hybrid, nine micro-hybrid and ten flowable-were therefore considered. Flexural strength, flexural modulus (E(flexural)), indentation modulus, Vickers hardness (HV) and creep were measured after the samples had been stored in water for 24 h at 37°C. Differences within the materials as well as within material categories were statistically analysed using one-way ANOVA with Tukey HSD post hoc test (α = 0.05) as well as partial eta-square statistics. RESULTS: The category of micro- and nano-hybrid RBCs performed in all properties superior compared to the flowable RBCs. The former two categories differ significantly only with regard to three parameters, with nano-hybrid RBCs showing higher HV respectively lower E(flexural) and filler weight. The micro-mechanical parameters proved to be more sensitive to differences in filler amount and RBCs type than the macro-mechanical properties. CLINICAL RELEVANCE: Only few differences were found between nano-hybrid and micro-hybrid RBCs as a material category and thus, from laboratory tests, no clear advantages in the mechanical stability in stress-bearing areas of nano-hybrid RBCs are expected clinically. Similar is valid for materials with new monomer formulation or photo-polymerization initiator technology. However, several of the measured nano-hybrid RBCs showed consistently higher mechanical properties than the mean values of the micro-hybrid RBCs.

Vinyl carbonates, vinyl carbamates, and related monomers: synthesis, polymerization, and application.

Although acrylates and methacrylates are the state-of-the-art monomers for protective and decorative coatings, skin and inhalation irritancy and potential cytotoxicity of monomers present serious health hazards. Monomers like vinyl carbonates or vinyl carbamates can overcome these problems with their generally lower cytotoxicity and yet similar photoreactivity to (meth)acrylates. The reviewed classes of monomers have not attracted industry's attention until now due to expensive synthetic methods though recently developed affordable routes offer prospect for their increasing use (88 references).

Comparison of mechanical properties of five commercial dental core build-up materials.

OBJECTIVE: This study aimed to evaluate and compare the mechanical properties of five commercial core materials using fracture toughness (FT), Knoop hardness number (KHN), diametral tensile strength (DTS), and dynamic elastic moduli (DEM). METHODS: Composite material specimens were produced (Rock Core, CosmeCore, ParaCore, MultiCore Flow, and Filtek Supreme Plus). The FT test (n = 15) was performed using notchless triangular prism (NTP) specimens. FT was determined using an Instron testing machine. KHN (n = 3) was evaluated using three indentations applied on each specimen. DTS test (n = 15) was measured using an Instron testing machine. The density. of the specimens (n = 3) was determined by water displacement method. Dynamic Young's, shear moduli, and Poisson's ratio (n = 3) were measured by an ultrasonic method. Statistical analysis was conducted using ANOVA and a Tukey B rank order test (P = 0.05). RESULTS: Rock Core presented the lowest FT values. Filtek Supreme Plus and CosmeCore exhibited significantly higher KHN values than the rest of the materials. CosmeCore had the highest DTS value, which was statistically significant only compared to Rock Core. For DEM, Filtek Supreme Plus exhibited significantly higher Young's and shear moduli than the rest of the materials (P < 0.05). CONCLUSIONS: Results demonstrated significant differences in the FT, KHN, and DTS values of the core build-up materials tested. According to the elastic behavior of the core composite materials, Rock Core had the lowest Young's values.

Chemoprevention of mouse lung and colon tumors by suberoylanilide hydroxamic acid and atorvastatin.

Atorvastatin and suberoylanilide hydroxamic acid (SAHA) were evaluated for chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 mg/kg atorvastatin, and combinations containing SAHA and atorvastatin administered in their diet. SAHA and both combinations, but not atorvastatin, decreased the multiplicity of lung tumors, including large adenomas and adenocarcinomas with the combinations demonstrating the greatest efficacy. In Experiment 2, lung tumors were induced by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol in strain A/J mice followed by 180 mg/kg atorvastatin, 500 mg/kg SAHA, or both drugs administered in the diet. SAHA and the combination of both drugs, but not atorvastatin alone, decreased the multiplicity of lung tumors and large tumors, with the combination demonstrating greater efficacy. In Experiment 3, lung tumors were induced by 1,2-dimethylhydrazine in Swiss-Webster mice followed by 160 mg/kg atorvastatin, 400 mg/kg SAHA, or a combination of both drugs administered in the diet. SAHA and the combination, but not atorvastatin, decreased the multiplicity of lung tumors with the combination demonstrating greater efficacy. The multiplicity of colon tumors was decreased by SAHA, atorvastatin, and the combination, without any significant difference in their efficacy. mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways. Atorvastatin demonstrated chemoprevention activity as indicated by the enhancement of the efficacy of SAHA to prevent mouse lung tumors.

Substituent effects on P2-cyclopentyltetrahydrofuranyl urethanes: design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors.

The design, synthesis, and biological evaluation of novel C3-substituted cyclopentyltetrahydrofuranyl (Cp-THF)-derived HIV-1 protease inhibitors are described. Various C3-functional groups on the Cp-THF ligand were investigated in order to maximize the ligand-binding site interactions in the flap region of the protease. Inhibitors 3c and 3d have displayed the most potent enzyme inhibitory and antiviral activity. Both inhibitors have maintained impressive activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 3c-bound HIV-1 protease revealed a number of important molecular insights into the ligand-binding site interactions.

Enhanced antibacterial effect of silver nanoparticles obtained by electrochemical synthesis in poly(amide-hydroxyurethane) media.

In the present study, we report enhanced antimicrobial properties of 29 and 23 nm silver nanoparticles (Ag NPs) obtained by electrochemical synthesis in poly(amide-hydroxyurethane) media. Antibacterial activity assessed by disk diffusion method indicates that silver nanoparticles produced inhibition zones for both Escherichia coli and Staphylococcus aureus depending on silver concentration. The bacterial growth curve performed in the presence of silver nanoparticles showed a stronger antibacterial effect at lower concentrations than those described in the earlier reports. The effect was both dose and size dependent and was more pronounced against Gram negative bacteria than Gram positive one. The smallest Ag NPs used had a bactericidal effect resulting in killing E. coli cells. Scanning electron microscopy analysis indicated major damage and morphology changes of the silver nanoparticles treated bacterial cells. The major mechanism responsible for the antibacterial effect probably consists in clusters formation and nanoparticles anchorage to the bacterial cell surface.

Investigating potency of TMC-126 against wild-type and mutant variants of HIV-1 protease: a molecular dynamics and free energy study.

A detailed computational study was performed to investigate the conformational changes of flap region and the mechanism underlying the binding of the inhibitor TMC-126 to HIV-1 protease (PR1) and its mutant variants through molecular dynamics simulations in conjunction with the molecular mechanics Poisson-Boltzmann (MM-PBSA) free energy calculation. Further, we have studied the effectiveness of the inhibitor against HIV-2 protease (PR2). The MM-PBSA calculation suggests that TMC-126 loses its potency against mutant variants and PR2 compared to wild-type PR1 mainly due to the loss in intermolecular electrostatic interactions. The potency of the inhibitor decreases in the order: wild type PR1 > M46L > MDR20 > I50V > PR2 > V32I > A28S. Our study reveals that the flap of PR1 adopts a semi-open conformation due to the mutation I50V or MDR20. The dissimilar nature of the movement of the flap tip of both monomers is evident from the dynamic cross-correlation map. The protein structural network analysis displays that mutation causes structural rearrangements and changes the communication path between residues. Overall, we believe our study may help explore and accelerate the development of novel HIV-1/HIV-2 protease inhibitors with better potency.

Long-term function of Hydrofit as hemostatic sealant: abridged republication.

The newly-designed hemostatic sealant, Hydrofit, was developed in Japan and consists of a urethane-based polymer without blood products. By applying Hydrofit gel to an anastomosis site on the aorta, water contact initiates a chemical change in the forming elastomer which adheres rapidly and tightly. We experienced an extirpation of Hydrofit gel that had been applied 4 years and 8 months previously in a 42-year-old female who underwent aortic valve replacement and graft replacement of the ascending aorta. The Hydrofit left around the aortic graft suture line was without infection and functioned very well as an elastic sealant for a long period.